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Volume 51(2); April 2019
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Obituary
In Memoriam: Waun Ki Hong, M.D. (August 13, 1942-January 2, 2019)
Hoon-Kyo Kim
Cancer Res Treat. 2019;51(2):415-416.   Published online March 18, 2019
DOI: https://doi.org/10.4143/crt.2019.149
PDFPubReaderePub

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  • Waun Ki Hong, MD, D.M.Sc (Hon) (1942–2019): A Mentor Who Left Behind a Legacy for Generations to Come
    Hyun Cheol Chung
    Yonsei Medical Journal.2020; 61(7): 557.     CrossRef
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Special Articles
Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2016
Kyu-Won Jung, Young-Joo Won, Hyun-Joo Kong, Eun Sook Lee, The Community of Population-Based Regional Cancer Registries
Cancer Res Treat. 2019;51(2):417-430.   Published online March 18, 2019
DOI: https://doi.org/10.4143/crt.2019.138
AbstractAbstract PDFPubReaderePub
Purpose
This study presents the 2016 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality.
Materials and Methods
Cancer incidence data from 1999 to 2016 were obtained from the Korea National Cancer Incidence Database and followed until December 31, 2017. Mortality data from 1983 to 2016 were obtained from Statistics Korea. The prevalence was defined as the number of cancer patients alive on January 1, 2017 among all cancer patients diagnosed since 1999. Crude and age-standardized rates (ASRs) for incidence, mortality, and prevalence and 5-year relative survivals were also calculated.
Results
Overall, 229,180 and 78,194 Koreans were newly diagnosed and died from cancer in 2016, respectively. The ASRs for cancer incidence and mortality in 2016 were 269.0 and 79.8 per 100,000 individuals, respectively. The all-cancer incidence rate increased significantly by 3.6% annually from 1999 to 2011 and started to decrease after 2011 (2011-2016; annual percent change, –3.1%). However, overall cancer mortality has decreased 2.7% annually since 2002. The 5-year relative survival rate for patients diagnosed with cancer between 2012 and 2016 was 70.6%, an improvement from the 41.2% for patients diagnosed between 1993 and 1995.
Conclusion
The cancer prevalence in Korea has increased very fast as survival has improved remarkably. The high prevalence of cancer emphasizes the need for comprehensive cancer control efforts in Korea.

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Prediction of Cancer Incidence and Mortality in Korea, 2019
Kyu-Won Jung, Young-Joo Won, Hyun-Joo Kong, Eun Sook Lee
Cancer Res Treat. 2019;51(2):431-437.   Published online March 18, 2019
DOI: https://doi.org/10.4143/crt.2019.139
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report on cancer incidence and mortality for the year 2019 to estimate Korea’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2016 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2017 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against observed years, then multiplying the projected age-specific rates by the age-specific population. The Joinpoint regression model was used to determine at which year the linear trend changed significantly; we used only the data of the latest trend.
Results
A total of 221,347 new cancer cases and 82,344 cancer deaths are expected to occur in Korea in 2019. The most common cancer sites thus far have been the lung, followed by the stomach, colon and rectum, breast, and liver. These five cancers represent half of the overall burden of cancer in Korea. For cancer associated mortality, the most common sites were lung, followed by the liver, colon and rectum, stomach, and pancreas.
Conclusion
The incidence rate of all cancer in Korea is estimated to decrease gradually. These up-todate estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

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Original Articles
Preclinical Efficacy of [V4 Q5 ]dDAVP, a Second Generation Vasopressin Analog, on Metastatic Spread and Tumor-Associated Angiogenesis in Colorectal Cancer
Juan Garona, Natasha T. Sobol, Marina Pifano, Valeria I. Segatori, Daniel E. Gomez, Giselle V. Ripoll, Daniel F. Alonso
Cancer Res Treat. 2019;51(2):438-450.   Published online June 1, 2018
DOI: https://doi.org/10.4143/crt.2018.040
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance.
Materials and Methods
Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo.
Results
In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells.
Conclusion
The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.

Citations

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Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells
Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2019;51(2):451-463.   Published online June 6, 2018
DOI: https://doi.org/10.4143/crt.2017.341
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.
Materials and Methods
The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
Results
AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
Conclusion
Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

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Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects
Chul Won Choi, Min Ho Jeong, You-Soo Park, Cheol-Hun Son, Hong-Rae Lee, Eun-Kyoung Koh
Cancer Res Treat. 2019;51(2):464-473.   Published online June 6, 2018
DOI: https://doi.org/10.4143/crt.2018.186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs).
Methods
and Materials CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system.
Results
Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group.
Conclusion
The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.

Citations

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Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer
Yusuke Okuda, Tomonori Yamada, Yoshikazu Hirata, Takaya Shimura, Ryuzo Yamaguchi, Eiji Sakamoto, Satoshi Sobue, Takahiro Nakazawa, Hiromi Kataoka, Takashi Joh
Cancer Res Treat. 2019;51(2):474-482.   Published online June 6, 2018
DOI: https://doi.org/10.4143/crt.2018.059
AbstractAbstract PDFPubReaderePub
Purpose
Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO.
Materials and Methods
Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups.
Results
Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%, p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658).
Conclusion
TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.

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The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer (99mTc-Dextran 40) in Breast
Xiao-Shan Cao, Guo-Ren Yang, Bin-Bin Cong, Peng-Fei Qiu, Yong-Sheng Wang
Cancer Res Treat. 2019;51(2):483-492.   Published online June 11, 2018
DOI: https://doi.org/10.4143/crt.2018.062
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast.
Materials and Methods
A small particle radiotracer (99mTc-Dextran 40) was prepared and tested. 99mTc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging.
Results
The radiochemical purity of 99mTc-Dextran 40 was > 95%. 99mTc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After 99mTc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then 99mTc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area.
Conclusion
The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

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EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy
Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):493-501.   Published online June 18, 2018
DOI: https://doi.org/10.4143/crt.2018.125
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

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Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib
Youjin Kim, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Cancer Res Treat. 2019;51(2):502-509.   Published online June 13, 2018
DOI: https://doi.org/10.4143/crt.2018.117
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib.
Materials and Methods
We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016.
Results
In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months).
Conclusion
First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

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Close layer
Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma
Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(2):510-518.   Published online June 13, 2018
DOI: https://doi.org/10.4143/crt.2018.226
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

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    Jan Jamroskovic, Mara Doimo, Karam Chand, Ikenna Obi, Rajendra Kumar, Kristoffer Brännström, Mattias Hedenström, Rabindra Nath Das, Almaz Akhunzianov, Marco Deiana, Kazutoshi Kasho, Sebastian Sulis Sato, Parham L. Pourbozorgi, James E. Mason, Paolo Medini
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A Comprehensive Assessment of the Racial and Ethnic Disparities in the Incidence of Gastric Cancer in the United States, 1992-2014
Qiang Yao, Xiaona Qi, Wen Cheng, Shao-Hua Xie
Cancer Res Treat. 2019;51(2):519-529.   Published online June 19, 2018
DOI: https://doi.org/10.4143/crt.2018.146
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the racial and ethnic disparities in the incidence of gastric cancer and their temporal trends in the United States.
Materials and Methods
Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities during 1992-2014 in the United States using a variety of disparity metrics.
Results
The age-standardized incidence rate of non-cardia gastric cancer was highest in Asian and Pacific Islanders, while the incidence of cardia gastric was highest in non-Hispanic whites in men and was similarly low in all groups in women. The incidence of non-cardia gastric cancer decreased in all groups over time, particularly in Asian and Pacific Islanders (on average by 3% per year). The incidence of cardia gastric remained relatively stable in virtually all racial/ethnic groups. The racial and ethnic disparities in gastric cancer incidence steadily decreased over time as measured on the absolute scale, which was mainly driven by the reduced disparities in non-cardia gastric cancer. The range difference in the incidence of gastric cancer decreased on average by 4.1% per year in men and by 2.6% per year in women from 1992 to 2014. The between group variance decreased by 5.6% per year in men and by 3.4% per year in women. The relative-scale disparity measures generally remained stable over time.
Conclusion
This study demonstrates decreased racial and ethnic disparities in the incidence of gastric cancer over time in the United States, particularly as measured on the absolute scale.

Citations

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  • Stomach Cancer Prediction Model (SCoPM): An approach to risk stratification in a diverse U.S. population
    Bechien U. Wu, Elizabeth Y. Dong, Qiaoling Chen, Tiffany Q. Luong, Eva Lustigova, Christie Y. Jeon, Wansu Chen, Hee-Taik Kang
    PLOS ONE.2024; 19(5): e0303153.     CrossRef
  • Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers
    Alyyah Malick, Jennifer S. Ferris, Chin Hur, Julian A. Abrams, Ali Soroush
    Clinical and Translational Gastroenterology.2024; 15(8): e00745.     CrossRef
  • Gastric cancer—Epidemiology, modifiable and non-modifiable risk factors, challenges and opportunities: An updated review
    Tajul Islam Mamun, Sabrina Younus, Md. Hashibur Rahman
    Cancer Treatment and Research Communications.2024; 41: 100845.     CrossRef
  • Racial/ethnic disparities in gastric cancer: A 15‐year population‐based analysis
    Maria Gonzalez‐Pons, Carlos R. Torres‐Cintrón, Marievelisse Soto‐Salgado, Yimari Vargas‐Ramos, Luis Perez‐Portocarrero, Douglas R. Morgan, Marcia Cruz‐Correa
    Cancer Medicine.2023; 12(2): 1860.     CrossRef
  • The uneven decline of gastric cancer in the USA: epidemiology of a health disparity
    Charles S. Rabkin
    The Lancet Regional Health - Americas.2023; 24: 100551.     CrossRef
  • The burden of stomach cancer mortality by county, race, and ethnicity in the USA, 2000–2019: a systematic analysis of health disparities
    Parkes Kendrick, Yekaterina O. Kelly, Mathew M. Baumann, Kelly Compton, Brigette F. Blacker, Farah Daoud, Zhuochen Li, Farah Mouhanna, Hasan Nassereldine, Chris Schmidt, Dillon O. Sylte, Lisa M. Force, Simon I. Hay, Erik J. Rodriquez, George A. Mensah, An
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    Kaio Evandro Cardoso Aguiar, Izabela De Sousa Oliveira, Amanda De Nazaré Cohen-Paes, Rita De Cássia Calderaro Coelho, Lui Wallacy Morikawa Souza Vinagre, Juliana Carla Gomes Rodrigues, André Maurício Ribeiro-Dos-Santos, Sandro José De Souza, Ândrea Ribeir
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    Gene T. Yoshikawa, Nicholas Simon, Ryon K. Nakasone, Jared D. Acoba
    Journal of Gastrointestinal Cancer.2022; 53(1): 144.     CrossRef
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    Yasuo Ohashi, Masataka Ikeda, Hideo Kunitoh, Mitsuru Sasako, Takuji Okusaka, Hirofumi Mukai, Keiichi Fujiwara, Mashio Nakamura, Mari S. Oba, Tetsuya Kimura, Kei Ibusuki, Atsushi Takita, Masato Sakon
    Thrombosis Research.2022; 213: 203.     CrossRef
  • Gastric Cancer
    Dalton A. Norwood, Eleazar Montalvan-Sanchez, Ricardo L. Dominguez, Douglas R. Morgan
    Gastroenterology Clinics of North America.2022; 51(3): 501.     CrossRef
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    John D. Karalis, Michelle R. Ju, John C. Mansour, Patricio M. Polanco, Adam C. Yopp, Herbert J. Zeh, Matthew R. Porembka, Sam C. Wang
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Increased Risk of Osteoporosis in Gastric Cancer Survivors Compared to General Population Control: A Study with Representative Korean Population
Su-Min Jeong, Dong Wook Shin, Ji Eun Lee, Sang-Man Jin, Sung Kim
Cancer Res Treat. 2019;51(2):530-537.   Published online June 27, 2018
DOI: https://doi.org/10.4143/crt.2018.164
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although several studies have suggested that osteoporosis is common in survivors of gastric cancer (GC), no study to date has directly assessed the risk for osteoporosis in GC survivors compared to matched controls. Thus, we aimed to investigate the relative risk for osteoporosis in survivors of GC compared to general population.
Materials and Methods
We used the Korea National Health and Nutrition Examination Survey data (2008-2011). Patients with a history of GC (n=94) were defined as case among 8,142 individuals over 50 years old who were evaluated by dual-energy X-ray absorptiometry. Controls (n=470) were matched to cases by age and sex in a 1:5 ratio. Osteopenia (–2.5 < T-score < –1.0) and osteoporosis (T-score ≤ –2.5) were defined.
Results
The prevalence of osteoporosis in GC survivors was 30.2%, which was significantly greater than that of controls (19.7%). In total, GC survivors had a 3.7-fold increased risk for osteoporosis compared to controls (p=0.021). In addition, the risk for osteoporosis of the total proximal femur total (TF) and femur neck (FN) was significantly increased among GC survivors compared to controls (adjusted relative risk, 4.64; 95% confidence interval, 1.16 to 18.6 in TF and adjusted relative risk, 3.58; 95% confidence interval, 1.19 to 10.8 in FN). Furthermore, we found sub-optimal daily calcium intake and mean serum levels of 25-hydroxy-vitamin D in both groups.
Conclusion
GC survivors are at significantly increased risk for osteoporosis, especially in the femur. Clinically, our finding supports the importance of screening bone health and adequate nutrient supplementation in survivors of GC.

Citations

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Diabetes Medication Use in Association with Survival among Patients of Breast, Colorectal, Lung, or Gastric Cancer
Michelle L. Baglia, Yong Cui, Tao Zheng, Gong Yang, Honglan Li, Mingrong You, Liling Xu, Harvey Murff, Yu-Tang Gao, Wei Zheng, Yong-Bing Xiang, Xiao-Ou Shu
Cancer Res Treat. 2019;51(2):538-546.   Published online July 2, 2018
DOI: https://doi.org/10.4143/crt.2017.591
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival.
Materials and Methods
The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models.
Results
After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival.
Conclusion
Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.

Citations

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Radiation Therapy Outcome and Clinical Features of Duodenal-Type Follicular Lymphoma
Hansang Lee, Dongryul Oh, Kyungmi Yang, Young Hyeh Ko, Yong Chan Ahn, Won Seog Kim, Seok Jin Kim
Cancer Res Treat. 2019;51(2):547-555.   Published online July 10, 2018
DOI: https://doi.org/10.4143/crt.2018.190
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Duodenal-type follicular lymphoma (FL) is a rare variant of FL. There is still no consensus on the initial treatment, and clinical features including endoscopic findings are not familiar to most physicians. The objective of this study was to evaluate the outcome of patients who were initially treated with radiation therapy for duodenal-type FL.
Materials and Methods
We retrospectively analyzed 20 patients who were consecutively diagnosed with duodenaltype FL between 2008 and 2017. All patients received radiation therapywith curative intent.
Results
The median age of the patients was 52 years (range, 26 to 66 years), and females were predominant. Most patients (n=18, 90%) had stage I disease, and were diagnosed by a regular health examination in an asymptomatic state. The histological grade was one in 19 patients (95%), and the endoscopic findings were diffuse nodular (n=8), whitish granular (n=8), and mixed pattern (n=4). Radiation therapy was delivered to 17 patients with 24 Gy in 12 fractions, and to three patients with 30.6-36 Gy in 18 fractions. All patients were evaluated with endoscopy for response to radiation therapy, and complete response was achieved in 19 patients (95%). At the time of analysis, all patients survived without any evidence of late toxicities related with radiation therapy.
Conclusion
Taken together, radiation therapy alone could be effective in controlling duodenal lesion. A further study with longer follow-up duration is warranted to confirm our findings.

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    Jan Bosch-Schips, Xenia Parisi, Fina Climent, Francisco Vega
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    Masuho Saburi, Yoshiyuki Kondo, Masao Ogata, Yasuhiro Soga, Miyuki Abe, Kuniko Takano, Kazuhiro Kohno, Takayuki Nagai, Toshiyuki Nakayama
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Health-Related Quality of Life Changes in Prostate Cancer Patients after Radical Prostatectomy: A Longitudinal Cohort Study
Dong Wook Shin, Sang Hyub Lee, Tae-Hwan Kim, Seok Joong Yun, Jong Kil Nam, Seung Hyun Jeon, Seung Chol Park, Seung Il Jung, Jong-Hyock Park, Jinsung Park
Cancer Res Treat. 2019;51(2):556-567.   Published online July 16, 2018
DOI: https://doi.org/10.4143/crt.2018.221
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Health-related quality of life (HRQOL) information related to radical prostatectomy (RP) is valuable for prostate cancer (PC) patients needing to make treatment decisions. We aimed to investigate HRQOL change in PC patients who underwent three types of RP (open, laparoscopic, or robotic) and compared their HRQOL with that of general population.
Materials and Methods
Patients were prospectively recruited between October 2014 and December 2015. European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) and PC-specific module (PR25) were administered before surgery (baseline) and at postoperative 3 and 12 months. At each time point, HRQOL was compared, and a difference of 10 out of 0-100 scale was considered clinically significant.
Results
Among 258 screened patients, 209 (41 open, 63 laparoscopic, and 105 robotic surgeries) were included. Compared to baseline, physical, emotional, and cognitive functioning improved at 12 months. Role functioning worsened at 3 months, but recovered to baseline at 12 months. Pain, insomnia, diarrhea, and financial difficulties also significantly improved at 12 months. Most PR25 scales excluding bowel symptoms deteriorated at 3 months. Urinary symptoms and incontinence aid recovered at 12 months, whereas sexual activity and sexual function remained poor at 12 months. Clinically meaningful differences in HRQOL were not observed according to RP modalities. Compared to the general population, physical and role functioning were significantly lower at 3 months, but recovered by 12 months. Social functioning did not recover.
Conclusion
Most HRQOL domains showed recovery within 12 months after RP, excluding sexual functioning and social functioning. Our findings may guide patients considering surgical treatment for PC.

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    Russell Seth Martins, Asad Saulat Fatimi, Omar Mahmud, Muhammad Umar Mahar, Arshia Jahangir, Kinza Jawed, Shalni Golani, Ayra Siddiqui, Syed Roohan Aamir, Ali Ahmad
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    İpek Köse Tosunöz, Sevgi Deniz Doğan, Şeyma Yurtseven, Sevban Arslan
    Cukurova Anestezi ve Cerrahi Bilimler Dergisi.2024; 7(3): 205.     CrossRef
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    Louise Dorner Østergaard, Mads Hvid Poulsen, Malene Eiberg Jensen, Lars Lund, Malene Grubbe Hildebrandt, Birgitte Nørgaard
    International Journal of Urological Nursing.2023; 17(1): 15.     CrossRef
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    Feiyang Wang, Jiajun Chen, Weihao Wang, Mengyao Li, Chao Peng, Shouhua Pan, Chuanchuan Zhan, Keyuan Zhao, Yulei Li, Lulu Zhang, Gang Xu, Jing Jin
    Urology.2023; 181: 105.     CrossRef
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    Josée Savard, Hanane Moussa, Jean‐François Pelletier, Pierre Julien, Louis Lacombe, Rabi Tiguert, Yves Caumartin, Thierry Dujardin, Paul Toren, Frédéric Pouliot, Michele Lodde, Yves Fradet, Karine Robitaille, Vincent Fradet
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    Amsalu Degu, Ermias Mergia Terefe, Eliab Seroney Some, Gobezie T Tegegne
    Cancer Management and Research.2022; Volume 14: 1525.     CrossRef
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    B. Steenstrup, M. Cartier, F.X. Nouhaud, G. Kerdelhue, M. Gilliaux
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    Yann Neuzillet, Mathieu Rouanne, Jean-François Dreyfus, Jean-Pierre Raynaud, Marc Schneider, Morgan Roupret, Sarah Drouin, Marc Galiano, Xavier Cathelinau, Thierry Lebret, Henry Botto
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    Jeong Hyun Kim, Yeon Soo Jang, Young Deuk Choi, Eui Geum Oh
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Verification of Low Risk for Perihippocampal Recurrence in Patients with Brain Metastases Who Received Whole-Brain Radiotherapy with Hippocampal Avoidance
Youngkyong Kim, Sung Hwan Kim, Jong Hoon Lee, Dae Gyu Kang
Cancer Res Treat. 2019;51(2):568-575.   Published online July 16, 2018
DOI: https://doi.org/10.4143/crt.2018.206
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to analyze the patterns of failure and survival outcome in patients with brain metastases who received whole-brain radiotherapy (WBRT) with hippocampal avoidance (HA) using simultaneous integrated boost (SIB) on metastatic brain tumors.
Materials and Methods
We retrospectively reviewed 42 patients treated with HA-WBRT for brain metastases. A total of 25 Gy for whole brain and 35-55 Gy for gross tumors were delivered with 10 fractionations. Local tumor and intracranial progression were defined as a recurrence or tumor progression in SIB field and any recurrence or tumor progression within whole brain, respectively. Progression in HA zone was defined as the recurrence within the area expanded 5 mm from HA zone.
Results
Median follow-up duration was 10.0 months (range, 4.1 to 56.4 months). Intracranial progression was observed in 13 patients (31.0%) and the median duration from the start of HA-WBRT to progression was 10.6 months (range, 0.9 to 33.0 months). Local tumor progression and new metastasis outside SIB field occurred in 10 patients (23.8%) and nine patients (21.4%), respectively. There was no isolated hippocampal metastasis, except only one patient (2.4%) with multiple metastases inside and outside HA zone simultaneously. Median survival time and intracranial progression-free survival rate at 1 year were 19.4 months (95% confidence interval [CI], 9.6 to 29.2) and 71.5%, respectively, and those for overall survival were 26.5 months (95% CI, 15.4 to 37.5) and 67.9%, respectively.
Conclusion
HA-WBRT was associated with low risk of new metastasis in HA region in the patients with brain metastases. These findings would serve as useful guidance on applying HA-WBRT in clinical practice.

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    Shari Wiegreffe, Gustavo Renato Sarria, Julian Philipp Layer, Egon Dejonckheere, Younèss Nour, Frederic Carsten Schmeel, Frank Anton Giordano, Leonard Christopher Schmeel, Ilinca Popp, Anca-Ligia Grosu, Eleni Gkika, Cas Stefaan Dejonckheere
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    Michael Mayinger, Johannes Kraft, Niklas Lohaus, Michael Weller, Daniel Schanne, Jana Heitmann, Jonas Willmann, Lotte Wilke, Jérôme Krayenbuehl, Stephanie Tanadini-Lang, Matthias Guckenberger, Nicolaus Andratschke
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Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells
Ying-ying Xu, Hai-ru Yu, Jia-yi Sun, Zhao Zhao, Shuang Li, Xin-feng Zhang, Zhi-xuan Liao, Ming-ke Cui, Juan Li, Chan Li, Qiang Zhang
Cancer Res Treat. 2019;51(2):576-592.   Published online July 18, 2018
DOI: https://doi.org/10.4143/crt.2018.100
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa.
Materials and Methods
PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels.
Results
PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment.
Conclusion
These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

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  • Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy
    Liang Yue, Tingting Gong, Wenhao Jiang, Liujia Qian, Wangang Gong, Yaoting Sun, Xue Cai, Heli Xu, Fanghua Liu, He Wang, Sainan Li, Yi Zhu, Zhiguo Zheng, Qijun Wu, Tiannan Guo
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    Xuemei Wang, Haihong Qian, Ling Yang, Shuangli Yan, Hua Wang, Xiu Li, Donghai Yang
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    Zhiliang Wang, Di Wu, Yue Zhang, Weibo Chen, Yang Yang, Yue Yang, Guangchen Zu, Yong An, Xianjun Yu, Yi Qin, Xiaowu Xu, Xuemin Chen
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    Qi Gu, Jiaochen Luan, Mengchi Yu, Jiadong Xia, Zengjun Wang
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    Sampurna Ghosh, Sk. Eashayan Tanbir, Tulika Mitra, Sib Sankar Roy
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    Chenlu Wu, Jiafei Ying, Mei Dai, Jing Peng, Danhua Zhang
    Journal of Cancer Research and Clinical Oncology.2022; 148(12): 3385.     CrossRef
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    Zining Liu, Weili Zhang, Biao Zhang, Shaomu Chen, Chunhua Ling
    Genetic Testing and Molecular Biomarkers.2022; 26(7-8): 351.     CrossRef
  • Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression
    Olivia K. Provance, Eric S. Geanes, Asona J. Lui, Anuradha Roy, Sean M. Holloran, Sumedha Gunewardena, Christy R. Hagan, Scott Weir, Joan Lewis-Wambi
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    Yang He, Peng Gong, Sitong Wang, Qing Xu, Jianhua Chen
    BioMedical Engineering OnLine.2021;[Epub]     CrossRef
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    Na Li, Yun Li, Hongbo Gao, Jing Li, Xiaoping Ma, Xiaomei Liu, Ping Gong, Xiaobin Cui, Yong Li
    Current Cancer Drug Targets.2021; 21(3): 254.     CrossRef
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    Rudolf Napieralski, Gabriele Schricker, Gert Auer, Michaela Aubele, Jonathan Perkins, Viktor Magdolen, Kurt Ulm, Moritz Hamann, Axel Walch, Wilko Weichert, Marion Kiechle, Olaf G. Wilhelm
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    Anna Díez-Villanueva, Rebeca Sanz-Pamplona, Robert Carreras-Torres, Ferran Moratalla-Navarro, M Henar Alonso, Laia Paré-Brunet, Susanna Aussó, Elisabet Guinó, Xavier Solé, David Cordero, Ramón Salazar, Maria Berdasco, Miguel A Peinado, Victor Moreno
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    Jing Luo, Yu Yao, Saiguang Ji, Qi Sun, Yang Xu, Kaichao Liu, Qiang Diao, Yong Qiang, Yi Shen
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  • 234 Download
  • 21 Web of Science
  • 17 Crossref
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Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database
Bum Sik Tae, Byung Jo Jeon, Seung Hun Shin, Hoon Choi, Jae Hyun Bae, Jae Young Park
Cancer Res Treat. 2019;51(2):593-602.   Published online July 18, 2018
DOI: https://doi.org/10.4143/crt.2018.119
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction.
Materials and Methods
Using the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT.
Results
During a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001).
Conclusion
Our results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

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    Denise Pergolizzi, Kathleen R. Flaherty, Rebecca M. Saracino, James C. Root, Elizabeth Schofield, Caroline Cassidy, Vani Katheria, Sunita K. Patel, William Dale, Christian J. Nelson
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Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients
Won Kyung Cho, Dongryul Oh, Eonju Lee, Tae Gyu Kim, Hyebin Lee, Heerim Nam, Jae Myoung Noh, Yong Chan Ahn
Cancer Res Treat. 2019;51(2):603-610.   Published online July 18, 2018
DOI: https://doi.org/10.4143/crt.2018.240
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients.
Materials and Methods
A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy.
Results
With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively.
Conclusion
The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

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Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus‒Positive and ‒Negative Relapsed or Refractory Non-Hodgkin Lymphomas
Seok-Jin Kim, Jiyeon Hyeon, Inju Cho, Young Hyeh Ko, Won Seog Kim
Cancer Res Treat. 2019;51(2):611-622.   Published online July 20, 2018
DOI: https://doi.org/10.4143/crt.2018.191
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor inhibits the interplay between PD1 of T-cell and programmed cell death ligand 1 (PDL1) on tumor cells. Although pembrolizumab has been tried to various subtypes of non-Hodgkin lymphoma (NHL), realworld data about the efficacy of pembrolizumab in NHL patients are limited.
Materials and methods
We analyzed the outcome of 30 relapsed or refractory NHL patients treated with pembrolizumab, and compared the outcome between Epstein-Barr virus (EBV)‒positive and negative subtypes because EBV infection of tumor cells can upregulate PDL1 expression.
Results
Seven patients with EBV-positive NHL showed a response including NK/T-cell lymphoma (6/14, 44%) and primary mediastinal B-cell lymphoma (1/4, 25%) whereas EBV-negative subtypes did not respond such as diffuse large B-cell lymphoma and T-lymphoblastic lymphoma. We also evaluated PDL1 expression using tumor tissue of 76 patients. High PDL1 expression (positive staining of > 50% of tumor cells) was more frequent in NK/T-cell lymphoma and primary mediastinal B-cell lymphoma than other subtypes. Thus, PDL1 expression was significantly higher in EBV-positive (18/32, 56%) than EBV-negative NHL (4/38, 11%, p < 0.001). Furthermore, NK/T-cell lymphoma patients with high PDL1 expression showed a higher response (4/6, 67%) than those with low PDL1 expression (1/5, 20%).
Conclusion
Pembrolizumab could be useful as a salvage treatment for relapsed or refractory EBV-positive NHL, especially NK/T-cell lymphoma. However, its efficacy in EBV-negative NHL with low or absent PDL1 expression is still not clear although pembrolizumab could be a potential treatment option for relapsed or refractory NHL.

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea
Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):623-631.   Published online July 23, 2018
DOI: https://doi.org/10.4143/crt.2018.151
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

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Effect of Estradiol in an Azoxymethane/Dextran Sulfate Sodium-Treated Mouse Model of Colorectal Cancer: Implication for Sex Difference in Colorectal Cancer Development
Hee Jin Son, Sung Hwa Sohn, Nayoung Kim, Ha-Na Lee, Sun Min Lee, Ryoung Hee Nam, Ji Hyun Park, Chin-Hee Song, Eun Shin, Hee Young Na, Joo Sung Kim, Dong Ho Lee, Young-Joon Surh
Cancer Res Treat. 2019;51(2):632-648.   Published online August 1, 2018
DOI: https://doi.org/10.4143/crt.2018.060
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model.
Materials and Methods
AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines.
Results
Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer.
Conclusion
The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.

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Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil-Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer
Jieun Lee, Dong-Min Kim, Ahwon Lee
Cancer Res Treat. 2019;51(2):649-663.   Published online July 31, 2018
DOI: https://doi.org/10.4143/crt.2018.270
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC).
Materials and Methods
Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain.
Results
Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002).
Conclusion
In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.

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Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases
Yi-Xin Zou, Jia Qiao, Hua-Yuan Zhu, Rui-Nan Lu, Yi Xia, Lei Cao, Wei Wu, Hui Jin, Wen-Jie Liu, Jin-Hua Liang, Jia-Zhu Wu, Li Wang, Lei Fan, Wei Xu, Jian-Yong Li
Cancer Res Treat. 2019;51(2):664-671.   Published online August 1, 2018
DOI: https://doi.org/10.4143/crt.2018.358
AbstractAbstract PDFPubReaderePub
Purpose
Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients.
Materials and Methods
In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients.
Results
The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70.
Conclusion
These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

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    Suyan Duan, Si Chen, Chen Chen, Fang Lu, Ying Pan, Yifei Lu, Qing Li, Simeng Liu, Bo Zhang, Huijuan Mao, Changying Xing, Yanggang Yuan
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    Yaqun Ding, Xiangyu Qi, Yang Li, Yanni Sun, Jia Wan, Chengxin Luo, Yarui Huang, Qingrong Li, Guixian Wu, Xiaoqing Zhu, Shuangnian Xu
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    Arina Onoprienko, Gerda Hofstetter, Tim Dorittke, Christine Bekos, Christoph Grimm, Mariella Polterauer, Thomas Bartl, Stephan Polterauer
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    Lin Fang, Fei-Hu Yan, Chao Liu, Jing Chen, Dan Wang, Chun-Hui Zhang, Chang-Jie Lou, Jie Lian, Yang Yao, Bo-Jun Wang, Rui-Yang Li, Shu-Ling Han, Yi-Bing Bai, Jia-Ni Yang, Zhi-Wei Li, Yan-Qiao Zhang
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    Shao-Jun Xu, Guo-Sheng Lin, Hong-Jian Ling, Ren-Jie Guo, Jie Chen, Yi-Ming Liao, Tao Lin, Yong-Jian Zhou
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Prediction of Acquired Taxane Resistance Using a Personalized Pathway-Based Machine Learning Method
Young Rae Kim, Dongha Kim, Sung Young Kim
Cancer Res Treat. 2019;51(2):672-684.   Published online August 10, 2018
DOI: https://doi.org/10.4143/crt.2018.137
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to develop and validate an individualized prediction model for automated detection of acquired taxane resistance (ATR).
Materials and Methods
Penalized regression, combinedwith an individualized pathway score algorithm,was applied to construct a predictive model using publically available genomic cohorts of ATR and intrinsic taxane resistance (ITR). To develop a model with enhanced generalizability, we merged multiple ATR studies then updated the learning parameter via robust cross-study validation.
Results
For internal cross-study validation, the ATR model produced a perfect performance with an overall area under the receiver operating curve (AUROC) of 1.000 with an area under the precision-recall curve (AUPRC) of 1.000, a Brier score of 0.007, a sensitivity and a specificity of 100%. The model showed an excellent performance on two independent blind ATR cohorts (overall AUROC of 0.940, AUPRC of 0.940, a Brier score of 0.127). When we applied our algorithm to two large-scale pharmacogenomic resources for ITR, the Cancer Genome Project (CGP) and the Cancer Cell Line Encyclopedia (CCLE), an overall ITR cross-study AUROC was 0.70, which is a far better accuracy than an almost random level reported by previous studies. Furthermore, this model had a high transferability on blind ATR cohorts with an AUROC of 0.69, suggesting that general predictive features may be at work across both ITR and ATR.
Conclusion
We successfully constructed a multi-study–derived personalized prediction model for ATR with excellent accuracy, generalizability, and transferability.

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Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Lei Wang, Zheng Wu, Dehuan Xie, Ruifang Zeng, Wanqin Cheng, Jiang Hu, Shaomin Huang, Shu Zhou, Rui Zhong, Yong Su
Cancer Res Treat. 2019;51(2):685-695.   Published online August 13, 2018
DOI: https://doi.org/10.4143/crt.2018.250
AbstractAbstract PDFPubReaderePub
Purpose
This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC).
Materials and Methods
From August 2009 to August 2013, patients with stage III–IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)–residual and gross tumor volume of cervical lymph node (GTVnd)–residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated.
Results
A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression-free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively.
Conclusion
After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy ofradiation dose to the tumorregression field may be feasible and need further investigation.

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Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Res Treat. 2019;51(2):696-705.   Published online August 13, 2018
DOI: https://doi.org/10.4143/crt.2018.249
AbstractAbstract PDFPubReaderePub
Purpose
Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Materials and Methods
Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively.
Results
DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells.
Conclusion
Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

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The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes
Xingen Wang, Julia Y. S. Tsang, Michelle A Lee, Yun-Bi Ni, Joanna H Tong, Siu-Ki Chan, Sai-Yin Cheung, Ka Fai To, Gary M Tse
Cancer Res Treat. 2019;51(2):706-717.   Published online August 23, 2018
DOI: https://doi.org/10.4143/crt.2018.316
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel nuclear receptor (NR) co-regulator, is highly expressed in breast cancer. We investigated its expression in breast cancer subtypes, in comparison with other breast markers as well as cancers from different sites. Its prognostic relevance with different subtypes and other NR expression was also examined in breast cancers.
Methods
Immunohistochemical analysis was performed on totally 1,944 cancers from six different organs.
Results
PELP1 expression rate was the highest in breast cancers (70.5%) among different cancers. Compared to GATA3, mammaglobin and gross cystic disease fluid protein 15, PELP1 was less sensitive than GATA3 for luminal cancers, but was the most sensitive for non-luminal cancers. PELP1 has low expression rate (<20%) in colorectal cancers, gastric cancers and renal cell carcinomas, but higher in lung cancers (49.1%) and ovarian cancers (42.3%). In breast cancer, PELP1 expression was an independent adverse prognostic factor for non-luminal cancers (disease-free survival [DFS]: hazard ratio [HR], 1.403; p=0.012 and breast cancer specific survival [BCSS]: HR, 1.443; p=0.015). Interestingly, its expression affected the prognostication of androgen receptor (AR). ARposPELP1lo luminal cancer showed the best DFS (log-rank=8.563, p=0.036) while ARnegPELP1hi non-luminal cancers showed the worst DFS (log-rank=9.536, p=0.023).
Conclusion
PELP1 is a sensitive marker for breast cancer, particularly non-luminal cases. However, its considerable expression in lung and ovarian cancers may limit its utility in differential diagnosis in some scenarios. PELP1 expression was associated with poor outcome in non-luminal cancers and modified the prognostic effects of AR, suggesting the potential significance of NR co-regulator in prognostication.

Citations

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    Terrance J. Lynn, Jianhui Shi, Haiyan Liu, Sara E. Monaco, Jeffrey W. Prichard, Fan Lin
    Archives of Pathology & Laboratory Medicine.2024; 148(1): e1.     CrossRef
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    Manar Moustafa, Magdy Ismael, Salah Mohamed, Abeer M. Hafez
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    KAI-XIANG HE, LIZHE XU, JIN-ZHUO NING, FAN CHENG
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    Paulina Miziak, Marzena Baran, Ewa Błaszczak, Alicja Przybyszewska-Podstawka, Joanna Kałafut, Jolanta Smok-Kalwat, Magdalena Dmoszyńska-Graniczka, Michał Kiełbus, Andrzej Stepulak
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  • Immunohistochemical study of proline, glutamic acid and leucine-rich protein 1 (PELP1) in correlation with guanine adenine thymine adenine family member 3 (GATA-3) receptors expression in breast carcinomas
    Ahmed A Elmetwally, Mennat Allah M Abdel-Hafeez, Makram M Hammam, Gamal A Hafez, Maha M Atwa, Mohammed K El-Kherbetawy
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    Manar Moustafa, Magdy Ismael, Salah Mohamed, Abeer Magdy
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    Qingqing Ding, Lei Huo, Yan Peng, Esther C. Yoon, Zaibo Li, Aysegul A. Sahin
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    Dongmei Zhang, Jiali Dai, Yu Pan, Xiuli Wang, Juanjuan Qiao, Hironobu Sasano, Baoshan Zhao, Keely M. McNamara, Xue Guan, Lili Liu, Yanzhi Zhang, Monica S. M. Chan, Shuwen Cao, Ming Liu, Sihang Song, Lin Wang
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    Frontiers in Oncology.2020;[Epub]     CrossRef
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A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13
Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):718-726.   Published online September 3, 2018
DOI: https://doi.org/10.4143/crt.2018.324
AbstractAbstract PDFPubReaderePub
Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

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    Cheng-Yu Chang, Chung-Yu Chen, Shih-Chieh Chang, Ching-Yi Chen, Yi-Chun Lai, Chun-Fu Chang, Yu-Feng Wei
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    Joseph N. Samuel, Christopher M. Booth, Elizabeth Eisenhauer, Michael Brundage, Scott R. Berry, Bishal Gyawali
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    Ruizhu Sun, Zhansheng Hou, Yankui Zhang, Bo Jiang
    Oncology Letters.2022;[Epub]     CrossRef
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    Wang Chun Kwok, Tan Fong Cheong, Ka Yan Chiang, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Terence Chi Chun Tam
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    Wang Chun Kwok, Ka Yan Chiang, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Terence Chi Chun Tam
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    Ellen Cusano, Chelsea Wong, Eddy Taguedong, Marcus Vaska, Tasnima Abedin, Nancy Nixon, Safiya Karim, Patricia Tang, Daniel Y. C. Heng, Doreen Ezeife
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    Wang Chun Kwok, David Chi Leung Lam, Ka Yan Chiang, James Chung Man Ho, Mary Sau Man Ip, Terence Chi Chun Tam
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