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Original Articles
Relationships between the Microbiome and Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
Hye In Lee, Bum-Sup Jang, Ji Hyun Chang, Eunji Kim, Tae Hoon Lee, Jeong Hwan Park, Eui Kyu Chie
Received June 2, 2024  Accepted December 13, 2024  Published online December 16, 2024  
DOI: https://doi.org/10.4143/crt.2024.521    [Accepted]
AbstractAbstract PDF
Purpose
This study aimed to investigate the dynamic changes in the microbiome of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), focusing on the relationship between the microbiome and response to nCRT.
Materials and Methods
We conducted a longitudinal study involving 103 samples from 26 patients with LARC. Samples were collected from both the tumor and normal rectal tissues before and after nCRT. Diversity, taxonomic, and network analyses were performed to compare the microbiome profiles across different tissue types, pre- and post-nCRT time-points, and nCRT responses.
Results
Between the tumor and normal tissue samples, no differences in microbial diversity and composition were observed. However, when pre- and post-nCRT samples were compared, there was a significant decrease in diversity, along with notable changes in composition. Non-responders exhibited more extensive changes in their microbiome composition during nCRT, characterized by an increase in pathogenic microbes. Meanwhile, responders had relatively stable microbiome communities with more enriched butyrate-producing bacteria. Network analysis revealed distinct patterns of microbial interactions between responders and non-responders, where butyrate-producing bacteria formed strong networks in responders, while opportunistic pathogens formed strong networks in non-responders. A Bayesian network model for predicting the nCRT response was established, with butyrate-producing bacteria playing a major predictive role.
Conclusion
Our study demonstrated a significant association between the microbiome and nCRT response in LARC patients, leading to the development of a microbiome-based response prediction model. These findings suggest potential applications of microbiome signatures for predicting and optimizing nCRT treatment in LARC patients.
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Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial
Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung
Received July 25, 2024  Accepted November 9, 2024  Published online November 12, 2024  
DOI: https://doi.org/10.4143/crt.2024.705    [Accepted]
AbstractAbstract PDF
Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.
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Low‒Dose Cyclophosphamide Enhances the Tumoricidal Effects of 5-Day Spacing Stereotactic Ablative Radiotherapy by Boosting Antitumor Immunity
Hyunkyung Kim, Seok-Joo Chun, Sojung Sun, Haeun Cho, Tae-Jin Kim, Yoon-Jin Lee, Eui Kyu Chie, Kwangmo Yang, Mi-Sook Kim
Received August 21, 2024  Accepted November 7, 2024  Published online November 8, 2024  
DOI: https://doi.org/10.4143/crt.2024.807    [Accepted]
AbstractAbstract PDF
Purpose
To investigate the potential role of low‒dose cyclophosphamide (Cy) as a radiosensitizer by evaluating its impact on the immune response and the abscopal effect of stereotactic ablative radiotherapy (SABR) through preclinical models.
Materials and Methods
CT26 tumors (immunologically hot) and 4T1 tumors (immunologically cold), grown in immunocompetent BALB/c and immunodeficient BALB/c‒nude mice, were irradiated with 20 Gy in two fractions with 5‒day spacing followed by intraperitoneal injections of 9 mg/kg Cy every 3 days. Immunological changes in CT26 tumors caused by the treatments were assessed using flow cytometry. Changes in the expression of HIF‒1α in tumors were also assessed. Splenocytes and bone marrow‒derived dendritic cells (DCs) were exposed to various concentrations of Cy to assess T cell proliferation and DC differentiation.
Results
The combination of Cy with RT (RT+Cy) significantly suppressed tumor growth compared to RT alone in immunocompetent mice, while that effect was not observed in immunodeficient mice. Additionally, RT+Cy effectively induced abscopal effects in hot and cold tumors, with increased CD8+ T cells in blood and tumors. Significantly higher expression levels of Granzyme B, IFN‒γ, and TNF‒α were observed in RT+Cy group compared to the RT alone group. In vitro data indicated that low‒dose Cy promotes DC differentiation. Low‒dose Cy suppressed the radiation‒induced upregulation of HIF‒1α in the tumors.
Conclusion
Low‒dose Cy enhances tumoricidal effects of 5‒day spacing high‒dose RT by increasing anti-tumor immune responses.
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Histological Assessment and Interobserver Agreement in Major Pathologic Response for Non–Small Cell Lung Cancer with Neoadjuvant Therapy
Sungjin Kim, Jeonghyo Lee, Jin-Haeng Chung
Received July 19, 2024  Accepted September 8, 2024  Published online September 9, 2024  
DOI: https://doi.org/10.4143/crt.2024.670    [Epub ahead of print]
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Major pathologic response (MPR), defined as ≤ 10% of residual viable tumor (VT), is a prognostic factor in non–small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction.
Materials and Methods
This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images.
Results
Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; intersection-over-union score, 0.92). Excellent agreement was achieved for VT (%) (intraclass correlation coefficient=0.959) and MPR using 10% cutoff (Fleiss’ kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p < 0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012).
Conclusion
While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.
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Gastrointestinal cancer
Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year
Youngun Kim, Jung Sun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon
Cancer Res Treat. 2024;56(4):1231-1239.   Published online May 27, 2024
DOI: https://doi.org/10.4143/crt.2024.237
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.
Materials and Methods
This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.
Results
Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.
Conclusion
The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.
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Hematologic malignancy
Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study
Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong Park, Yeung-Chul Mun, Cheolwon Suh, the Korean Society of Hematology Lymphoma Working Party
Cancer Res Treat. 2023;55(4):1355-1362.   Published online March 30, 2023
DOI: https://doi.org/10.4143/crt.2023.271
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL).
Materials and Methods
Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy.
Results
Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016).
Conclusion
Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.
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Breast cancer
Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor–Positive and HER-2–Negative Breast Cancer with Neoadjuvant Chemotherapy
Eun-Gyeong Lee, Dong-Eun Lee, Hyun hee Kim, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Heejung Chae, Sung Hoon Sim, Keun Seok Lee, Youngmee Kwon, So-Youn Jung
Cancer Res Treat. 2023;55(2):542-550.   Published online September 8, 2022
DOI: https://doi.org/10.4143/crt.2022.834
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors.
Materials and Methods
We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR.
Results
Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022).
Conclusion
AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Citations

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  • The prevalence and clinical significance of residual occult breast cancer after neoadjuvant chemotherapy: reassessing surgical pathology in cases initially described as pathological complete response
    Di Ai, Eliel N Arrey, Lauren M Postlewait, Yuan Gao, Xiaoxian Li
    Histopathology.2025;[Epub]     CrossRef
  • Neo-adjuvant therapies for ER positive/HER2 negative breast cancers: from chemotherapy to hormonal therapy, CDK inhibitors, and beyond
    Athina Stravodimou, Ioannis A. Voutsadakis
    Expert Review of Anticancer Therapy.2024; 24(3-4): 117.     CrossRef
  • Luminal androgen receptor subtype and tumor-infiltrating lymphocytes groups based on triple-negative breast cancer molecular subclassification
    Miseon Lee, Tae-Kyung Yoo, Byung Joo Chae, Ahwon Lee, Yoon Jin Cha, Jieun Lee, Sung Gwe Ahn, Jun Kang
    Scientific Reports.2024;[Epub]     CrossRef
  • Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma
    Adil Aziz Khan, Sana Ahuja, Kiruthikasri G., Sufian Zaheer
    Indian Journal of Surgical Oncology.2024; 15(4): 802.     CrossRef
  • Biomarkers and translational research approaches in breast cancer—an update
    Angelika M. Starzer, Anna S. Berghoff, Rupert Bartsch
    memo - Magazine of European Medical Oncology.2023; 16(1): 42.     CrossRef
  • Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy
    Zhendong Shi, Yingxue Liu, Shichao Zhang, Shuanglong Cai, Xu Liu, Jie Meng, Jin Zhang
    Discover Oncology.2023;[Epub]     CrossRef
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Gastrointestinal cancer
A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer
Hyunji Jo, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Jeong Il Yu, Hee Chul Park, Doo Ho Choi, Yoonah Park, Yong Beom Cho, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Won Ki Kang
Cancer Res Treat. 2023;55(1):189-195.   Published online June 8, 2022
DOI: https://doi.org/10.4143/crt.2021.1527
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).
Materials and Methods
Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.
Results
Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.
Conclusion
The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Citations

Citations to this article as recorded by  
  • Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies
    Haiyang Sun, Shuhuai Meng, Junyu Chen, Qianbing Wan
    Journal of Functional Biomaterials.2023; 14(4): 194.     CrossRef
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Gynecologic cancer
Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation
Yuchun Wei, Chuqing Wei, Liang Chen, Ning Liu, Qiuxiang Ou, Jiani C. Yin, Jiaohui Pang, Zhenhao Fang, Xue Wu, Xiaonan Wang, Dianbin Mu, Yang Shao, Jinming Yu, Shuanghu Yuan
Cancer Res Treat. 2022;54(4):1209-1218.   Published online January 17, 2022
DOI: https://doi.org/10.4143/crt.2021.963
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.
Materials and Methods
A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.
Results
Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse.
Conclusion
We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Citations

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  • Comprehensive characterization of PKHD1 mutation in human colon cancer
    Lu Han, Fangming Gong, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Yue Wang, Daizhenru Wang, Yulan Sun, Peng Li
    Cancer Medicine.2024;[Epub]     CrossRef
  • PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer
    Wenhan Li, Yuhui Huang, Man Xiao, Jing Zhao, Shi Du, Zehua Wang, Sha Hu, Lu Yang, Jing Cai
    iScience.2024; 27(3): 109160.     CrossRef
  • Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real‐world cohort analysis
    Yi Sun, Shilei Qin, Song Wang, Jiaohui Pang, Qiuxiang Ou, Weiquan Liang, Hai Zhong
    The Journal of Pathology: Clinical Research.2024;[Epub]     CrossRef
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    Cong Wang, Lijun Liu, Xia Li, Jia Lei, Yiqian Li, Zhibo Shen, Huirong Shi, Yan Cheng
    Future Oncology.2024; 20(20): 1415.     CrossRef
  • A biomarker exploration in small-cell lung cancer for brain metastases risk and prophylactic cranial irradiation therapy efficacy
    Li Li, Ning Liu, Tao Zhou, Xueting Qin, Xiaoyu Song, Song Wang, Jiaohui Pang, Qiuxiang Ou, Yong Wang, Dexian Zhang, Jiaran Li, Fuhao Xu, Shuming Shi, Jinming Yu, Shuanghu Yuan
    Lung Cancer.2024; 196: 107959.     CrossRef
  • Prospects of POLD1 in Human Cancers: A Review
    Michał Gola, Przemysław Stefaniak, Janusz Godlewski, Barbara Jereczek-Fossa, Anna Starzyńska
    Cancers.2023; 15(6): 1905.     CrossRef
  • Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma
    Su Ir Lyu, Felix C. Popp, Adrian Georg Simon, Anne Maria Schultheis, Thomas Zander, Caroline Fretter, Wolfgang Schröder, Christiane J. Bruns, Thomas Schmidt, Alexander Quaas, Karl Knipper
    Scientific Reports.2023;[Epub]     CrossRef
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Gastrointestinal cancer
Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy
Jesang Yu, Jong Hoon Kim, Sung-Bae Kim, Sook Ryun Park, Young-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Ho June Song, Kye Jin Song, Jeong Yun Jang, Yoon Young Jo, Ye Jin Yoo
Cancer Res Treat. 2022;54(4):1148-1156.   Published online December 20, 2021
DOI: https://doi.org/10.4143/crt.2021.885
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery.
Materials and Methods
We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW).
Results
The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001).
Conclusion
In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Citations

Citations to this article as recorded by  
  • Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis
    Junli Ke, Yujie Xie, Shenyang Huang, Wei Wang, Zhengang Zhao, Wanli Lin
    Asian Journal of Surgery.2024; 47(9): 3827.     CrossRef
  • Multi-disciplinary management of esophageal carcinoma: Current practices and future directions
    Chanyoot Bandidwattanawong
    Critical Reviews in Oncology/Hematology.2024; 197: 104315.     CrossRef
  • Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma
    Tae Hee Hong, Tae Ho Kim, Genehee Lee, Jeonghee Yun, Yeong Jeong Jeon, Junghee Lee, Sumin Shin, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong-Mu Sun, Dongryul Oh, Hong Kwan Kim
    European Journal of Cardio-Thoracic Surgery.2024;[Epub]     CrossRef
  • Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study
    Tongpeng Xu, Jianan Bai, Kun Zhao, Xiaofeng Chen, Shuhui Wang, Shusheng Zhu, Chongqi Sun, Chenhui Zhao, Ting Wang, Ling Zhu, Meizhen Hu, Fei Pang, Junling Zhang, Wei Wang, Yongqian Shu, Fang Li, Yue Zhou
    Annals of Surgical Oncology.2024; 31(13): 9321.     CrossRef
  • Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
    Rakesh Acharya, Ananya Mahapatra, Henu Kumar Verma, L. V. K. S. Bhaskar
    Current Oncology.2023; 30(11): 9542.     CrossRef
  • Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
    Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
    Gastroenterology Report.2023;[Epub]     CrossRef
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Lung and Thoracic cancer
The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non–Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors
Xiaoyan Sun, Yingnan Feng, Bin Zhang, Wuhao Huang, Xiaoliang Zhao, Hua Zhang, Dongsheng Yue, Changli Wang
Cancer Res Treat. 2022;54(4):1017-1029.   Published online November 23, 2021
DOI: https://doi.org/10.4143/crt.2021.1007
AbstractAbstract PDFPubReaderePub
Purpose
The aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC).
Materials and Methods
Resectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery.
Results
A total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group.
Conclusion
High NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

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    Calogera Claudia Spagnolo, Francesco Pepe, Giuliana Ciappina, Francesco Nucera, Paolo Ruggeri, Andrea Squeri, Desirèe Speranza, Nicola Silvestris, Umberto Malapelle, Mariacarmela Santarpia
    Critical Reviews in Oncology/Hematology.2024; 197: 104332.     CrossRef
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    Mingming Hu, Xiaomi Li, Haifeng Lin, Baohua Lu, Qunhui Wang, Li Tong, Hongxia Li, Nanying Che, Shaojun Hung, Yi Han, Kang Shi, Chenghai Li, Hongmei Zhang, Zhidong Liu, Tongmei Zhang
    International Journal of Surgery.2024; 110(4): 2275.     CrossRef
  • Dynamics of peripheral blood inflammatory index predict tumor pathological response and survival among patients with locally advanced non-small cell lung cancer who underwent neoadjuvant immunochemotherapy: a multi-cohort retrospective study
    Wenyu Zhai, Chao Zhang, Fangfang Duan, Jingdun Xie, Shuqin Dai, Yaobin Lin, Qihang Yan, Bingyu Rao, Liang Li, Yuheng Zhou, Zerui Zhao, Hao Long, Junye Wang
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology
    Xiao Zhang, Zhenyu Lin, Yuan Feng, Zhaoguo Lin, Kaixiong Tao, Tao Zhang, Xiaoli Lan
    Journal of Nuclear Medicine.2024; 65(10): 1548.     CrossRef
  • Radiomics nomogram combined with clinical factors for predicting pathological complete response in resectable esophageal squamous cell carcinoma
    Zihao Lu, Yongsen Li, Wenxuan Hu, Yonghao Cao, Xin Lv, Xinyu Jia, Shiyu Shen, Jun Zhao, Chun Xu
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Zhao Shuang, Xiong Xingyu, Cheng Yue, Yu Mingjing
    The Clinical Respiratory Journal.2024;[Epub]     CrossRef
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    Huan Zhang, Fan Lin, Zhuocai Wang
    BMC Cancer.2023;[Epub]     CrossRef
  • Development and validation of a radiomics-based nomogram for predicting a major pathological response to neoadjuvant immunochemotherapy for patients with potentially resectable non-small cell lung cancer
    Chaoyuan Liu, Wei Zhao, Junpeng Xie, Huashan Lin, Xingsheng Hu, Chang Li, Youlan Shang, Yapeng Wang, Yingjia Jiang, Mengge Ding, Muyun Peng, Tian Xu, Ao’ran Hu, Yuda Huang, Yuan Gao, Xianling Liu, Jun Liu, Fang Ma
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Prognostic role of preoperative inflammatory markers in postoperative patients with colorectal cancer
    Zilong Xiao, Xinxin Wang, Xiaoxiao Chen, Jiawei Zhou, Haitao Zhu, Jiangnan Zhang, Wensheng Deng
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy
    Wen-Yu Zhai, Fang-Fang Duan, Yao-Bin Lin, Yong-Bin Lin, Ze-Rui Zhao, Jun-Ye Wang, Bing-Yu Rao, Lie Zheng, Hao Long
    Journal of Inflammation Research.2023; Volume 16: 3329.     CrossRef
  • The predictive value of 18F-FDG PET/CT combined with inflammatory index for major pathological reactions in resectable NSCLC receiving neoadjuvant immunochemotherapy
    Xiaoqin Yin, Jian Li, Bei Chen, Kehuang Liu, Shuo Hu
    Lung Cancer.2023; 186: 107389.     CrossRef
  • Efficacy, safety, and survival of neoadjuvant immunochemotherapy in operable non-small cell lung cancer: a systematic review and meta-analysis
    Yue Zheng, Baijie Feng, Jingyao Chen, Liting You
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC
    Ana Oitabén, Pablo Fonseca, María J. Villanueva, Carme García-Benito, Aida López-López, Alberto Garrido-Fernández, Clara González-Ojea, Laura Juaneda-Magdalena, Martín E. Lázaro, Mónica Martínez-Fernández
    Cancers.2022; 14(11): 2626.     CrossRef
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Gynecologic cancer
Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy
Aeran Seol, Ga Won Yim, Joo Yeon Chung, Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong Sang Song
Cancer Res Treat. 2022;54(4):1219-1229.   Published online November 17, 2021
DOI: https://doi.org/10.4143/crt.2021.1010
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).
Materials and Methods
Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients’ survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.
Results
A total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167).
Conclusion
Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.

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  • CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression
    Chunyan Huang, Li Qin, Sailan Chen, Qin Huang
    Anti-Cancer Drugs.2022;[Epub]     CrossRef
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General
Radiation Response Prediction Model Based on Integrated Clinical and Genomic Data Analysis
Bum-Sup Jang, Ji-Hyun Chang, Seung Hyuck Jeon, Myung Geun Song, Kyung-Hun Lee, Seock-Ah Im, Jong-Il Kim, Tae-You Kim, Eui Kyu Chie
Cancer Res Treat. 2022;54(2):383-395.   Published online August 24, 2021
DOI: https://doi.org/10.4143/crt.2021.759
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings.
Materials and Methods
Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response.
Results
Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83.
Conclusion
Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

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  • Estimating the risk and benefit of radiation therapy in (y)pN1 stage breast cancer patients: A Bayesian network model incorporating expert knowledge (KROG 22–13)
    Bum-Sup Jang, Seok-Joo Chun, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Computer Methods and Programs in Biomedicine.2024; 245: 108049.     CrossRef
  • Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model
    Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Cancers.2024; 16(8): 1494.     CrossRef
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    I-Shiow Jan, Hui Ju Ch’ang
    Radiation Oncology.2023;[Epub]     CrossRef
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    Seung Hyuck Jeon, Eui Kyu Chie
    Cancer Medicine.2023; 12(7): 8981.     CrossRef
  • Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma
    Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li, Hui-Ju Ch’ang
    Cancers.2023; 15(21): 5212.     CrossRef
  • 5,769 View
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  • 5 Web of Science
  • 5 Crossref
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Gastrointestinal cancer
Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Res Treat. 2022;54(2):541-553.   Published online August 6, 2021
DOI: https://doi.org/10.4143/crt.2021.473
AbstractAbstract PDFPubReaderePub
Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

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  • Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
    Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
    Cancers.2024; 16(9): 1690.     CrossRef
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    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
    Cancer Control.2024;[Epub]     CrossRef
  • The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
    Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
    Frontiers in Cell and Developmental Biology.2023;[Epub]     CrossRef
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    Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
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  • Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
    Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
    Viruses.2022; 14(7): 1372.     CrossRef
  • Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
    Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
    Cancers.2022; 15(1): 93.     CrossRef
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  • 229 Download
  • 10 Web of Science
  • 7 Crossref
Close layer
Association between the Persistence of Obesity and the Risk of Gastric Cancer: A Nationwide Population-Based Study
Joo Hyun Lim, Cheol Min Shin, Kyung-Do Han, Seung Woo Lee, Eun Hyo Jin, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee
Cancer Res Treat. 2022;54(1):199-207.   Published online May 4, 2021
DOI: https://doi.org/10.4143/crt.2021.130
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There remains controversy about relationship between obesity and gastric cancer. We aimed to examine the association using obesity-persistence.
Materials and Methods
We analyzed a nationwide population-based cohort which underwent health check-up between 2009 and 2012. Among them, those who had annual examinations during the last 5 years were selected. Gastric cancer risk was compared between those without obesity during the 5 years (never-obesity group) and those with obesity diagnosis during the 5 years (non-persistent obesity group; persistent obesity group).
Results
Among 2,757,017 individuals, 13,441 developed gastric cancer after median 6.78 years of follow-up. Gastric cancer risk was the highest in persistent obesity group (incidence rate [IR], 0.89/1,000 person-years; hazard ratio [HR], 1.197; 95% confidence interval [CI], 1.117 to 1.284), followed by non-persistent obesity group (IR, 0.83/1,000 person-years; HR, 1.113; 95% CI, 1.056 to 1.172) compared with never-obesity group. In subgroup analysis, this positive relationship was true among those < 65 years old and male. Among heavy-drinkers, the impact of obesity-persistence on the gastric cancer risk far increased (non-persistent obesity: HR, 1.297; 95% CI, 1.094 to 1.538; persistent obesity: HR, 1.351; 95% CI, 1.076 to 1.698).
Conclusion
Obesity-persistence is associated with increased risk of gastric cancer in a dose-response manner, especially among male < 65 years old. The risk raising effect was much stronger among heavy-drinkers.

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  • Diagnosis of gastric cancer in role of endoscopic imaging techniques in artificial intelligence and machine learning applications: An overview
    Pooja K., Kishore Kanna R., G. Li, U. Subramaniam, M. Sekar
    E3S Web of Conferences.2024; 491: 03016.     CrossRef
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    Graeme A. Macdonald, James A. Thomas, Christine Dalais, Bradley J. Kendall, Aaron P. Thrift
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    Lujie Zhao, Yuling Kan, Lu Wang, Jiquan Pan, Yun Li, Haiyan Zhu, Zhongfa Yang, Lin Xiao, Xinhua Fu, Fujun Peng, Haipeng Ren
    Oncology Reports.2024;[Epub]     CrossRef
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    Wing Ching Chan, Iona Millwood, Christiana Kartsonaki, Huaidong Du, Daniel Schmidt, Rebecca Stevens, Junshi Chen, Pei Pei, Canqing Yu, Dianjianyi Sun, Jun Lv, Xianyong Han, Liming Li, Zhengming Chen, Ling Yang
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    Narges Azizi, Moein Zangiabadian, Golnoosh Seifi, Afshan Davari, Elham Yekekhani, Seyed Amir Ahmad Safavi-Naini, Nathan A. Berger, Mohammad Javad Nasiri, Mohammad-Reza Sohrabi
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    Qinli Xie, Yangjun He, Danni Zhou, Yi Jiang, Ying Deng, Ruoqing Li
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    Mi Jin Oh, Kyungdo Han, Bongseong Kim, Joo Hyun Lim, Bokyung Kim, Sang Gyun Kim, Soo-Jeong Cho
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    Taewan Kim, Seung In Seo, Kyung Joo Lee, Chan Hyuk Park, Tae Jun Kim, Jinseob Kim, Woon Geon Shin
    Antibiotics.2022; 11(8): 1052.     CrossRef
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    Yanyan Li, Jungang Zhao, Renpin Chen, Shengwei Chen, Yilun Xu, Weiyang Cai
    BMC Cancer.2022;[Epub]     CrossRef
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    Susanna C. Larsson, Nikolaos Spyrou, Christos S. Mantzoros
    Metabolism.2022; 137: 155326.     CrossRef
  • FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells
    Jijun Yan, Juntao Liu, Zhengbin Huang, Wenwei Huang, Jianfa Lv
    Human Cell.2021; 34(6): 1755.     CrossRef
  • 7,827 View
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Close layer
Genitourinary Cancer
Use of Gemcitabine plus Carboplatin is Associated with Poor Outcomes in Urothelial Carcinoma Patients with Chronic Kidney Disease Stage 4-5
Hyung-Don Kim, Hyeon-Su Im, Jwa Hoon Kim, Hyehyun Jeong, Shin Kyo Yoon, Inkeun Park, Jae Lyun Lee
Cancer Res Treat. 2021;53(4):1166-1173.   Published online March 4, 2021
DOI: https://doi.org/10.4143/crt.2021.091
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the clinical outcomes with gemcitabine-carboplatin (GCb), the standard treatment for patients with advanced urothelial carcinoma (UC) who are ineligible for cisplatin-based regimens, in advanced UC patients with a glomerular filtration rate (GFR) < 30 mL/min.
Materials and Methods
A retrospective cohort study involving GCb-treated advanced UC patients with GFR < 60 mL/min (n=89) was performed. Clinical outcomes were compared between subgroups with GFR < 30 mL/min and GFR ≥ 30 mL/min but < 60 mL/min.
Results
Most baseline characteristics were comparable between the two subgroups. Patients with GFR < 30 mL/min had a significantly lower objective response rate (12.5%) compared to those with higher GFR levels (56.7%) (p=0.004). The number of GCb cycles was significantly lower in patients with GFR < 30 mL/min (median 2 cycles) than in those with higher GFR levels (median 6 cycles) (p=0.002). Compared to those with GFR ≥ 30 mL/min but < 60 mL/min, patients with GFR < 30 mL/min showed significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.001 for both). Further stratification of patient subgroups according to their GFR (i.e., GFR ≥ 45 mL/min but < 60 mL/min vs. GFR ≥ 30 mL/min but < 45 mL/min vs. GFR < 30 mL/min) revealed significantly different PFS and OS (p < 0.001 for both).
Conclusion
The use of GCb is discouraged in advanced UC patients with GFR < 30 mL/min. Alternative therapeutic approaches with better efficacy are warranted for these patients.

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  • Onconephrology: mitigation of renal injury in chemotherapy administration
    Umut Selamet, Rebecca S. Ahdoot, Reed Salasnek, Lama Abdelnour, Ramy M. Hanna
    Current Opinion in Nephrology & Hypertension.2024; 33(2): 257.     CrossRef
  • Management of bladder cancer in older patients
    Shingo Hatakeyama, Shintaro Narita, Kazutaka Okita, Takuma Narita, Hiromichi Iwamura, Naoki Fujita, Junichi Inokuchi, Yoshiyuki Matsui, Hiroshi Kitamura, Chikara Ohyama
    Japanese Journal of Clinical Oncology.2022; 52(3): 203.     CrossRef
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Gastrointestinal cancer
Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma Incorporating Hematological Biomarkers
Yingjia Wu, Jinbin Chen, Lei Zhao, Qiaoqiao Li, Jinhan Zhu, Hong Yang, Suping Guo, Mian Xi
Cancer Res Treat. 2021;53(1):172-183.   Published online September 4, 2020
DOI: https://doi.org/10.4143/crt.2020.594
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to develop a nomogram for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) by integrating hematological biomarkers and clinicopathological characteristics.
Materials and Methods
Between 2003 and 2017, 306 ESCC patients who underwent neoadjuvant CRT followed by esophagectomy were analyzed. Besides clinicopathological factors, hematological parameters before, during, and after CRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and internally validated.
Results
Absolute lymphocyte count (ALC), lymphocyte to monocyte ratio, albumin, hemoglobin, white blood cell, neutrophil, and platelet count generally declined, whereas neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increased significantly following neoadjuvant CRT. After surgery, 124 patients (40.5%) achieved a pCR. The pCR group demonstrated significantly more favorable survival than the non-pCR group. On multivariate analysis, significant factors associated with pCR included sex, chemotherapy regimen, post-CRT endoscopic finding, pre-CRT NLR, ALC nadir during CRT, and post-CRT PLR, which were incorporated into the prediction model. The nomogram indicated good accuracy in predicting pCR, with a C-index of 0.75 (95% confidence interval, 0.71 to 0.78).
Conclusion
Female, chemotherapy regimen of cisplatin/vinorelbine, negative post-CRT endoscopic finding, pre-CRT NLR (≤ 2.1), ALC nadir during CRT (> 0.35 ×109/L), and post-CRT PLR (≤ 83.0) were significantly associated with pCR in ESCC patients treated with neoadjuvant CRT. A nomogram incorporating hematological biomarkers to predict pCR was developed and internally validated, showing good predictive performance.

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  • CT-based deep learning radiomics and hematological biomarkers in the assessment of pathological complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma: A two-center study
    Meng Zhang, Yukun Lu, Hongfu Sun, Chuanke Hou, Zichun Zhou, Xiao Liu, Qichao Zhou, Zhenjiang Li, Yong Yin
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    Ting Qian, Delin Liu, Guochun Cao, Zhipeng Chen, Qin Zhang
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    Guihong Liu, Tao Chen, Xin Zhang, Binbin Hu, Jiayun Yu
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    Xing Gao, Hidde C G Overtoom, Ben M Eyck, Shi-Han Huang, Daan Nieboer, Pieter C van der Sluis, Sjoerd M Lagarde, Bas P L Wijnhoven, Yin-Kai Chao, Jan J B van Lanschot
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    Chien-Ming Lo, Hung-I. Lu, Yu-Ming Wang, Yen-Hao Chen, Yu Chen, Li-Chun Chen, Shau-Hsuan Li
    Perioperative Medicine.2024;[Epub]     CrossRef
  • Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery
    Ji Yong Kim, Jae Kwang Yun, Yong-Hee Kim, Seung-il Park, Jeong Hoon Lee, Hwoon-Yong Jung, Gin Hyug Lee, Ho June Song, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Sung-Bae Kim, Kyung-Ja Cho, Jin-Sook Ryu, Jong Hoon Kim, Jihoon Kang, Sook Ryun Park, Hyeong Ryul
    Annals of Surgical Oncology.2024; 31(10): 6662.     CrossRef
  • The relationship between systemic immune-inflammation indexes and treatment response in locally advanced esophageal cancer
    Esra KEKİLLİ, Ebru ATASEVER AKKAŞ, Serab UYAR, Emre YEKEDÜZ
    Anatolian Current Medical Journal.2023; 5(1): 53.     CrossRef
  • A Novel Predictor of Pathologic Complete Response for Neoadjuvant Immunochemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
    Yalan Yang, Dao Xin, Huike Wang, Lulu Guan, Xiangrui Meng, Taiying Lu, Xiwen Bai, Feng Wang
    Journal of Inflammation Research.2023; Volume 16: 1443.     CrossRef
  • Gut microbiome can predict chemoradiotherapy efficacy in patients with esophageal squamous cell carcinoma
    Takuma Sasaki, Yasunori Matsumoto, Kentaro Murakami, Satoshi Endo, Takeshi Toyozumi, Ryota Otsuka, Kazuya Kinoshita, Jie Hu, Shinichiro Iida, Hiroki Morishita, Yuri Nishioka, Akira Nakano, Masaya Uesato, Hisahiro Matsubara
    Esophagus.2023; 20(4): 691.     CrossRef
  • Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort
    Wei‐Xiang Qi, Xiaoyan Wang, Chengqiang Li, Shuyan Li, Huan Li, Feifei Xu, Jiayi Chen, Shengguang Zhao, Hecheng Li
    Thoracic Cancer.2023; 14(17): 1556.     CrossRef
  • Prognostic analysis and treatment utilization of different treatment strategies in elderly esophageal cancer patients with distant metastases: a SEER database analysis
    Lian-Qiang Han, Ting-Ting Cui, Nian-Jun Xiao, Wen Li
    Journal of Cancer Research and Clinical Oncology.2023; 149(17): 15413.     CrossRef
  • Effect of dynamic platelet-to-lymphocyte ratio on the prognosis of patients with esophageal squamous cell carcinoma receiving chemoradiotherapy
    Dan He, Shulan Du, Songyuan He, Hao Song, Bo Pu, Guojun Zhang, Chuan Yang
    Medicine.2023; 102(49): e36554.     CrossRef
  • Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
    Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
    Gastroenterology Report.2023;[Epub]     CrossRef
  • Impact of Platelets to Lymphocytes Ratio and Lymphocytes during Radical Concurrent Radiotherapy and Chemotherapy on Patients with Nonmetastatic Esophageal Squamous Cell Carcinoma
    Yaotian Zhang, Ning Han, Xue Zeng, Chaonan Sun, Shichen Sun, Xinchi Ma, Yanyu Zhang, Zhuang Liu, Zilan Qin, Hong Guo, Yubing Li, Na Zhang, Bruno Vincenzi
    Journal of Oncology.2022; 2022: 1.     CrossRef
  • Serum Anti-BRAT1 is a Common Molecular Biomarker for Gastrointestinal Cancers and Atherosclerosis
    Liubing Hu, Jiyue Liu, Hideaki Shimada, Masaaki Ito, Kazuo Sugimoto, Takaki Hiwasa, Qinghua Zhou, Jianshuang Li, Si Shen, Hao Wang
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma
    Noel E Donlon, Maria Davern, Fiona O’Connell, Andrew Sheppard, Aisling Heeran, Anshul Bhardwaj, Christine Butler, Ravi Narayanasamy, Claire Donohoe, James J Phelan, Niamh Lynam-Lennon, Margaret R Dunne, Stephen Maher, Jacintha O’Sullivan, John V Reynolds,
    World Journal of Gastroenterology.2022; 28(21): 2302.     CrossRef
  • Pathologic Complete Response Prediction to Neoadjuvant Immunotherapy Combined with Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: Real-World Evidence from Integrative Inflammatory and Nutritional Scores
    Jifeng Feng, Liang Wang, Xun Yang, Qixun Chen, Xiangdong Cheng
    Journal of Inflammation Research.2022; Volume 15: 3783.     CrossRef
  • The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non–Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors
    Xiaoyan Sun, Yingnan Feng, Bin Zhang, Wuhao Huang, Xiaoliang Zhao, Hua Zhang, Dongsheng Yue, Changli Wang
    Cancer Research and Treatment.2022; 54(4): 1017.     CrossRef
  • The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy
    Jin Zhou, Hai-Ping Lin, Xin Xu, Xiao-Hang Wang, Ling Rong, Yao Zhang, Lei Shen, Lei Xu, Wei-Ting Qin, Qing Ye, Xiu-Mei Ma, Yong-Rui Bai
    Frontiers in Immunology.2022;[Epub]     CrossRef
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High Systemic Inflammation Response Index (SIRI) Indicates Poor Outcome in Gallbladder Cancer Patients with Surgical Resection: A Single Institution Experience in China
Lejia Sun, Wenmo Hu, Meixi Liu, Yang Chen, Bao Jin, Haifeng Xu, Shunda Du, Yiyao Xu, Haitao Zhao, Xin Lu, Xinting Sang, Shouxian Zhong, Huayu Yang, Yilei Mao
Cancer Res Treat. 2020;52(4):1199-1210.   Published online July 21, 2020
DOI: https://doi.org/10.4143/crt.2020.303
AbstractAbstract PDFPubReaderePub
Purpose
The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC.
Materials and Methods
From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility.
Results
One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649).
Conclusion
The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Citations

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  • SIRI and SII as potential biomarkers of disease activity and lupus nephritis in systemic lupus erythematosus
    Chi-Hui Yang, Xin-Yi Wang, Yi-Hui Zhang, Ning Ding
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    Jin Cheng, Honglei Ju, Guixiang Wang, Chiyi He, Wei Wang
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    颖 张
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    Lin Xie, Qun Wang, Hengcheng Lu, Maobin Kuang, Shiming He, Guobo Xie, Guotai Sheng, Shuhua Zhang, Wei Wang, Yang Zou
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    Tian Wang, Duo Zhang, Di Tang, Yu Heng, Li-ming Lu, Lei Tao
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  • Preoperative Fibrinogen Albumin Ratio is an Effective Biomarker for Prognostic Evaluation of Gallbladder Carcinoma After Radical Resection: A 10-Year Retrospective Study at a Single Center
    Qi Li, Jian Zhang, Qi Gao, Jialu Fu, Mengke Li, Hengchao Liu, Chen Chen, Dong Zhang, Zhimin Geng
    Journal of Inflammation Research.2023; Volume 16: 677.     CrossRef
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    Songping Cui, Shuang Cao, Qing Chen, Qiang He, Ren Lang
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Assessment of aggregate index of systemic inflammation and systemic inflammatory response index in dry age-related macular degeneration: a retrospective study
    Naif S. Sannan
    Frontiers in Medicine.2023;[Epub]     CrossRef
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    Jing Wang, Xue-Li Ding, Zi-Bin Tian
    World Chinese Journal of Digestology.2023; 31(9): 369.     CrossRef
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    Huan Wang, Yuting Shi, Yueli Shi, Mengqing Cao, Long Zhang, Yuan Wu, Yun Xu, Kai Wang, Xianwu Weng, Bing Niu
    International Journal of Clinical Practice.2023; 2023: 1.     CrossRef
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    Wenbin Lu, Shengwei Lin, Cheng Wang, Peipei Jin, Jinjun Bian
    International Journal of General Medicine.2023; Volume 16: 5355.     CrossRef
  • Systemic Inflammation Response Index (SIRI) Independently Predicts Survival in Advanced Lung Adenocarcinoma Patients Treated with First-Generation EGFR-TKIs
    Shun Jiang, Sisi Wang, Qianqian Wang, Chao Deng, Yuhua Feng, Fang Ma, Jin'an Ma, Xianling Liu, Chunhong Hu, Tao Hou
    Cancer Management and Research.2021; Volume 13: 1315.     CrossRef
  • The Prognostic Value of Preoperative Systemic Inflammatory Response Index (SIRI) in Patients With High-Grade Glioma and the Establishment of a Nomogram
    Qian He, Longhao Li, Qinglan Ren
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Yu-Jia Shen, Li-Qiang Qian, Zheng-Ping Ding, Qing-Quan Luo, Heng Zhao, Wu-Yan Xia, Yuan-Yuan Fu, Wen Feng, Qin Zhang, Wen Yu, Xu-Wei Cai, Xiao-Long Fu
    Frontiers in Oncology.2021;[Epub]     CrossRef
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Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2020;52(3):945-956.   Published online April 17, 2020
DOI: https://doi.org/10.4143/crt.2020.080
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.
Materials and Methods
In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.
Results
AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.
Conclusion
Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

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    Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
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    Yoshihito Morimoto, Kimihiko Takada, Ami Nakano, Osamu Takeuchi, Kazuhiro Watanabe, Masayoshi Hirohara, Yutaka Masuda
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    Kyoung-Seok Oh, Ah-Rong Nam, Ju-Hee Bang, Yoojin Jeong, Sea Young Choo, Hyo Jung Kim, Su In Lee, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
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    Giulia Anichini, Chiara Raggi, Mirella Pastore, Laura Carrassa, Luisa Maresca, Enrica Crivaro, Tiziano Lottini, Lea Duwe, Jesper B. Andersen, Lorenzo Tofani, Luca Di Tommaso, Jesus M. Banales, Annarosa Arcangeli, Fabio Marra, Barbara Stecca
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  • Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma
    Zhengbo Hu, Lugen Li, Wenxing Lan, Xiao Wei, Xiangyuan Wen, Penghuan Wu, Xianliao Zhang, Xinhua Xi, Yufa Li, Liqi Wu, Wenhu Li, Xiaohong Liao
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    Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
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Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma
Miao Xue, Yanqin Wu, Wenzhe Fan, Jian Guo, Jialiang Wei, Hongyu Wang, Jizhou Tan, Yu Wang, Wang Yao, Yue Zhao, Jiaping Li
Cancer Res Treat. 2020;52(3):925-937.   Published online March 30, 2020
DOI: https://doi.org/10.4143/crt.2019.533
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

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    Qi Fan, Pengcheng Wei, Delin Ma, Qian Cheng, Jie Gao, Jiye Zhu, Zhao Li
    Surgery Open Science.2025; 23: 16.     CrossRef
  • TP53 Mutation Predicts Worse Survival and Earlier Local Progression in Patients with Hepatocellular Carcinoma Treated with Transarterial Embolization
    Ken Zhao, Anita Karimi, Luke Kelly, Elena Petre, Brett Marinelli, Erica S. Alexander, Vlasios S. Sotirchos, Joseph P. Erinjeri, Anne Covey, Constantinos T. Sofocleous, James J. Harding, William Jarnagin, Carlie Sigel, Efsevia Vakiani, Etay Ziv, Hooman Yar
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    Wei-Li Xia, Shi-Jun Xu, Yuan Guo, Xiao-Hui Zhao, Hong-Tao Hu, Yan Zhao, Quan-Jun Yao, Lin Zheng, Dong-Yang Zhang, Chen-Yang Guo, Wei-Jun Fan, Hai-Liang Li
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  • Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma
    Tian-Cheng Wang, Tian-Zhi An, Jun-Xiang Li, Zi-Shu Zhang, Yu-Dong Xiao
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    Zhan-Qi Wei, Yue-Wei Zhang
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    Young Chang, Soung Won Jeong, Jae Young Jang, Yong Jae Kim
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PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy
Sanxing Guo, Sibylle Loibl, Gunter von Minckwitz, Silvia Darb-Esfahani, Bianca Lederer, Carsten Denkert
Cancer Res Treat. 2020;52(3):689-696.   Published online February 4, 2020
DOI: https://doi.org/10.4143/crt.2019.497
AbstractAbstract PDFPubReaderePub
Purpose
PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CAmutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Materials and Methods
A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.
Results
Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).
Conclusion
TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

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Carcinoembryonic Antigen Improves the Performance of Magnetic Resonance Imaging in the Prediction of Pathologic Response after Neoadjuvant Chemoradiation for Patients with Rectal Cancer
Gyu Sang Yoo, Hee Chul Park, Jeong Il Yu, Doo Ho Choi, Won Kyung Cho, Young Suk Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yong Beom Cho, Yoon Ah Park, Kyoung Doo Song, Seok-Hyung Kim, Sang Yun Ha
Cancer Res Treat. 2020;52(2):446-454.   Published online September 25, 2019
DOI: https://doi.org/10.4143/crt.2019.261
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levels in improving the performance of magnetic resonance imaging (MRI) for the prediction of pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectal cancer.
Materials and Methods
We retrospectively reviewed the medical records of 524 rectal cancer patients who underwent NCRT and total mesorectal excision between January 2009 and December 2014. The performances of MRI with or without CEA parameters (initial CEA and CEA dynamics) for prediction of pathologic tumor response grade (pTRG) were compared by receiver-operating characteristic analysis with DeLong’s method. Cox regression was used to identify the independent factors associated to pTRG and disease-free survival (DFS) after NCRT.
Results
The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis, poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) and the mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed association with poor pTRG. The mrTRG plus CEA parameters showed significantly improved performances in the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEA were also identified as independent factors associated with DFS. The initial CEA further discriminated DFS in the subgroups with good mrTRG or that without mrMFI.
Conclusion
The CEA parameters significantly improved the performance of MRI in the prediction of pTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initial CEA level in the groups with favorable MRI parameters.

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Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Cancer Res Treat. 2020;52(1):149-166.   Published online June 25, 2019
DOI: https://doi.org/10.4143/crt.2019.183
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.
Materials and Methods
We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings.
Results
In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
Conclusion
Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

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Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer
Ah-Rong Nam, Mei Hua Jin, Ji Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2019;51(3):1167-1179.   Published online December 3, 2018
DOI: https://doi.org/10.4143/crt.2018.526
AbstractAbstract PDFPubReaderePub
Purpose
The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor.
Materials and Methods
A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings.
Results
Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug.
Conclusion
In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.

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  • “Convex Lens” of DNA damage: A nanomedicine enhances anti-PD-1 immunotherapy as immunogenic cell death inducer for “cold” melanoma
    Wenjun Wang, Yu Liu, Dong Chen, Jiajia Pang, Chunyu Lai, Mingbao Gu, Meilun Zhai, Qian Yu, Yang Wang, Xuanwen Bao, Yangyang Li, Xiaomeng Dai, Dong Chen, Peng Zhao, Jinghong Xu, Rui Lei
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    Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
    Cancer Research and Treatment.2022; 54(2): 541.     CrossRef
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    Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
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    Longxiang Huang, Qin Ye, Chunlin Lan, Xiaohui Wang, Yihua Zhu
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    Longxiang Huang, Zhenni Wei, Xiaohui Wang, Chunlin Lan, Yihua Zhu, Qin Ye
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  • Synergism of AZD6738, an ATR Inhibitor, in Combination with Belotecan, a Camptothecin Analogue, in Chemotherapy-Resistant Ovarian Cancer
    Jin Hur, Mithun Ghosh, Tae Heon Kim, Nahee Park, Kamal Pandey, Young Bin Cho, Sa Deok Hong, Nar Bahadur Katuwal, Minsil Kang, Hee Jung An, Yong Wha Moon
    International Journal of Molecular Sciences.2021; 22(3): 1223.     CrossRef
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    Ah-Rong Nam, Jeesun Yoon, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Jae-Min Kim, Tae-Yong Kim, Do-Youn Oh
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    Sara Hamis, James Yates, Mark A. J. Chaplain, Gibin G. Powathil
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    Giulia Anichini, Laura Carrassa, Barbara Stecca, Fabio Marra, Chiara Raggi
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    Sofia Genta, Federica Martorana, Anastasios Stathis, Ilaria Colombo
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    Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
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Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer
Se Ik Kim, Minsun Song, Suhyun Hwangbo, Sungyoung Lee, Untack Cho, Ju-Hyun Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Dae-Shik Suh, Taesung Park, Yong-Sang Song
Cancer Res Treat. 2019;51(3):1144-1155.   Published online November 20, 2018
DOI: https://doi.org/10.4143/crt.2018.508
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC.
Materials and Methods
We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied.
Results
The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively.
Conclusion
We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

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    Qingyuan Cheng, Liman Li, Mingxia Yu
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  • Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma
    Suhyun Hwangbo, Se Ik Kim, Ju-Hyun Kim, Kyung Jin Eoh, Chanhee Lee, Young Tae Kim, Dae-Shik Suh, Taesung Park, Yong Sang Song
    Cancers.2021; 13(8): 1875.     CrossRef
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    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Ji-Bin Liu, Kai-Jian Chu, Chang-Chun Ling, Ting-Miao Wu, Hui-Min Wang, Yi Shi, Zhi-Zhen Li, Jing-Han Wang, Zhi-Jun Wu, Xiao-Qing Jiang, Gao-Ren Wang, Yu-Shui Ma, Da Fu
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    Michael A. Bookman
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Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma
In Kyoung Hwang, Seung Sook Paik, Seung Hyeun Lee
Cancer Res Treat. 2019;51(1):158-168.   Published online April 2, 2018
DOI: https://doi.org/10.4143/crt.2018.084
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma.
Materials and Methods
We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups.
Results
A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group.
Conclusion
Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.

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    Lovisa Karlsson, Isabelle Öhrnberg, Shumaila Sayyab, David Martínez-Enguita, Mika Gustafsson, Patricia Espinoza, Melissa Méndez-Aranda, Cesar Ugarte-Gil, Lameck Diero, Ronald Tonui, Jakob Paues, Maria Lerm
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    Giulia Polinário, Laura Maria Duran Gleriani Primo, Maiara Alane Baraldi Cerquetani Rosa, Freddy Humberto Marin Dett, Paula Aboud Barbugli, Cesar Augusto Roque-Borda, Fernando Rogério Pavan
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Redefining the Positive Circumferential Resection Margin by Incorporating Preoperative Chemoradiotherapy Treatment Response in Locally Advanced Rectal Cancer: A Multicenter Validation Study
Joo Ho Lee, Eui Kyu Chie, Seung-Yong Jeong, Tae-You Kim, Dae Yong Kim, Tae Hyun Kim, Sun Young Kim, Ji Yeon Baek, Hee Jin Chang, Min Ju Kim, Sung Chan Park, Jae Hwan Oh, Sung Hwan Kim, Jong Hoon Lee, Doo Ho Choi, Hee Chul Park, Sung-Bum Kang, Jae-Sung Kim
Cancer Res Treat. 2018;50(2):506-517.   Published online May 24, 2017
DOI: https://doi.org/10.4143/crt.2016.607
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer.
Materials and Methods
Clinical data of 197 patientswith positive circumferentialresection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009were collected forthis multicenter validation study. All patients underwent median 50.4Gy radiationwith concurrentfluoropyrimidine based chemotherapy. Treatmentresponse was dichotomized to good response, including treatmentresponse of grade 2 or 3, and poor response, including grade 0 or 1.
Results
After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poorresponderswith involved margin hadworst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001).
Conclusion
Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.

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  • Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial
    Philippe Rouanet, Eric Rullier, Bernard Lelong, Philippe Maingon, Jean-Jacques Tuech, Denis Pezet, Florence Castan, Stephanie Nougaret
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Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy
Hyun Ju Kim, Yang-Gun Suh, Yong Chan Lee, Sang Kil Lee, Sung Kwan Shin, Byung Chul Cho, Chang Geol Lee
Cancer Res Treat. 2017;49(3):669-677.   Published online October 6, 2016
DOI: https://doi.org/10.4143/crt.2016.354
AbstractAbstract PDFPubReaderePub
Purpose
The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT).
Materials and Methods
Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients.
Results
There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups.
Conclusion
A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

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    Renxian Xie, Qingxin Cai, Tong Chen, Hongxin Huang, Chuangzhen Chen
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    Jing You, Shuchai Zhu, Jiancheng Li, Jie Li, Junyue Shen, Yidian Zhao, Xiaomin Li, Lin Jia, Qingshan Li, Jun Yang, Yiqun Wu, Wenbin Shen, Haishan Wu, Xueqin Wu, Xiaomin Wang, Yaqiong Ren, Jun He, Pingping Lin, Guangying Zhu, Anhui Shi
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    Julian Mangesius, Katharina Hörmandinger, Robert Jäger, Sergej Skvortsov, Marlen Plankensteiner, Martin Maffei, Thomas Seppi, Daniel Dejaco, Matthias Santer, Manuel Sarcletti, Ute Ganswindt
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    Feihong Xie, Tingting Liu, Xinran Wang, Jinling Dong, Wei Huang, Hongfu Sun
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    Wei Zhang, Qing Xie, Bifa Zhu, Xiaokang Wang, Ling He, Yong Zhang
    Medicine.2022; 101(16): e29166.     CrossRef
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    Yujin Xu, Baiqiang Dong, Weiguo Zhu, Jiancheng Li, Rong Huang, Zongwen Sun, Xinmei Yang, Liping Liu, Han He, Zhongxing Liao, Ni Guan, Yue Kong, Wanwei Wang, Jianxiang Chen, Huijuan He, Guoqin Qiu, Ming Zeng, Juan Pu, Wangyuan Hu, Yong Bao, Zhigang Liu, Ju
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Interactome Analysis Reveals that Heterochromatin Protein 1γ (HP1γ) Is Associated with the DNA Damage Response Pathway
Hongtae Kim, Jae Duk Choi, Byung-Gyu Kim, Ho Chul Kang, Jong-Soo Lee
Cancer Res Treat. 2016;48(1):322-333.   Published online March 6, 2015
DOI: https://doi.org/10.4143/crt.2014.294
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Heterochromatin protein 1γ (HP1γ) interacts with chromosomes by binding to lysine 9-methylated histone H3 or DNA/RNA. HP1γ is involved in various biological processes. The purpose of this study is to gain an understanding of how HP1γ functions in these processes by identifying HP1γ-binding proteins using mass spectrometry.
Materials and Methods
We performed affinity purification of HP1γ-binding proteins using G1/S phase or prometaphase HEK293T cell lysates that transiently express mock or FLAG-HP1γ. Coomassie staining was performed for HP1γ-binding complexes, using cell lysates prepared by affinity chromatography FLAG-agarose beads, and the bands were digested and then analyzed using a mass spectrometry.
Results
We identified 99 HP1γ-binding proteins with diverse cellular functions, including spliceosome, regulation of the actin cytoskeleton, tight junction, pathogenic Escherichia coli infection, mammalian target of rapamycin signaling pathway, nucleotide excision repair, DNA replication, homologous recombination, and mismatch repair.
Conclusion
Our results suggested that HP1γ is functionally active in DNA damage response via proteinprotein interaction.

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Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy
Jung Ran Choi, Jeong-Oh Kim, Dae Ryong Kang, Jung-Young Shin, Xiang Hua Zhang, Ji Eun Oh, Ji-Young Park, Kyoung-Ah Kim, Jin-Hyoung Kang
Cancer Res Treat. 2015;47(3):509-517.   Published online December 16, 2014
DOI: https://doi.org/10.4143/crt.2014.012
AbstractAbstract PDFPubReaderePub
Purpose
Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. Materials and Methods In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). Results Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. Conclusion Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy

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