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Original Articles
- Genitourinary cancer
- Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy
- Bokyung Ahn, Doeun Kim, Kye Jin Park, Ja-Min Park, Sun Young Yoon, Bumsik Hong, Yong Mee Cho, Deokhoon Kim
- Cancer Res Treat. 2024;56(3):856-870. Published online December 18, 2023
- DOI: https://doi.org/10.4143/crt.2023.1150
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Abstract
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Supplementary Material
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ePub - Purpose
In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.
Materials and Methods
Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).
Conclusion
According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively. -
Citations
Citations to this article as recorded by
- Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience
Jianping Zhao, Yuan Shen, Ming Guo, Surena F Matin, Donna E Hansel, Charles C Guo
American Journal of Clinical Pathology.2024;[Epub] CrossRef - Clinical significance of tumor location for ureteroscopic tumor grading in upper tract urothelial carcinoma
Satoshi Katayama, benjamin pradere, Nico C. Grossmann, Aaron M. Potretzke, Stephen J Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John Sfakianos, Andrea Mari, Zine-Eddine Khene, David D'Andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel He
Journal of Endourology.2024;[Epub] CrossRef
- Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience
- 2,592 View
- 110 Download
- 2 Web of Science
- 2 Crossref
- Lung and Thoracic cancer
- Integrin αvβ3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer
- Shinkyo Yoon, Hannah Yang, Hyun-Min Ryu, Eunjin Lee, Yujin Jo, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Wanlim Kim, Kyung Hae Jung, Sook Ryun Park, Eun Kyung Choi, Sang-We Kim, Kang-Seo Park, Dae Ho Lee
- Cancer Res Treat. 2022;54(3):767-781. Published online September 30, 2021
- DOI: https://doi.org/10.4143/crt.2021.651
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.
Materials and Methods
We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.
Results
We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.
Conclusion
The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC. -
Citations
Citations to this article as recorded by- Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR‐Mutated Lung Cancer Cells Resistant to Osimertinib
Yu‐Ting Kang, Hui‐Yi Chang, Ya‐Chu Hsieh, Chia‐Hsuan Chou, I‐Lun Hsin, Jiunn‐Liang Ko
Environmental Toxicology.2024; 39(12): 5238. CrossRef - Junctional adhesion molecular 3 (JAM3) is a novel tumor suppressor and improves the prognosis in breast cancer brain metastases via the TGF-β/Smad signal pathway
Kaitao Zhu, Shiwei Li, Hongru Yao, Jilong Hei, WenGuo Jiang, Tracey Martin, Shanyi Zhang
Journal of Neuro-Oncology.2024; 170(2): 331. CrossRef - Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence
Bashar Alhasan, Marina Mikeladze, Irina Guzhova, Boris Margulis
Cancer and Metastasis Reviews.2023; 42(1): 217. CrossRef
- Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR‐Mutated Lung Cancer Cells Resistant to Osimertinib
- 8,675 View
- 272 Download
- 2 Web of Science
- 3 Crossref
- Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer
- Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang
- Cancer Res Treat. 2018;50(4):1324-1330. Published online January 8, 2018
- DOI: https://doi.org/10.4143/crt.2017.526
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin. -
Citations
Citations to this article as recorded by- A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study
Hui-Jen Tsai, Shih-Hung Yang, Chin-Fu Hsiao, Hsiang-Fong Kao, Yung-Yeh Su, Yan-Shen Shan, Chia-Jui Yen, Jeng-Shiun Du, Chiun Hsu, I-Chen Wu, Li-Tzong Chen
The Oncologist.2024; 29(10): e1396. CrossRef - Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study
Hyehyun Jeong, Bum Jun Kim, Choong-kun Lee, Inkeun Park, Dae Young Zang, Hye Jin Choi, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Sung-Hoon Moon, Kyu-pyo Kim, Zev Wainberg, Baek-Yeol Ryoo, Changhoon Yoo
European Journal of Cancer.2024; 208: 114194. CrossRef - Redox-responsive engineered hybrid nanomedicine for gallbladder cancer therapy via hyaluronic acid depletion
Jinglin Zou, Cong Jiang, Xianglong Li, Tianyu Zhong, Shuqi Wang, Bo Wang, Dapeng Zhang, Ji-Na Hao, Yuanyuan Cao, Mengjia Guan, Peng Zhang, Bin Dai, Yongsheng Li
Applied Materials Today.2023; 30: 101707. CrossRef - Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective
Cindy Neuzillet, Pascal Artru, Eric Assenat, Julien Edeline, Xavier Adhoute, Jean-Christophe Sabourin, Anthony Turpin, Romain Coriat, David Malka
Targeted Oncology.2023; 18(1): 51. CrossRef - Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis
Junya Toyoda, Kota Sahara, Tomoaki Takahashi, Kentaro Miyake, Yasuhiro Yabushita, Yu Sawada, Yuki Homma, Ryusei Matsuyama, Itaru Endo, Timothy Pawlik
Journal of Clinical Medicine.2023; 12(7): 2654. CrossRef - Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
Jean marc Phelip, Jérôme Desrame, Julien Edeline, Emilie Barbier, Eric Terrebonne, Pierre Michel, Hervé Perrier, Laetitia Dahan, Vincent Bourgeois, Faiza Khemissa Akouz, Emilie Soularue, Valérie Lebrun Ly, Yann Molin, Thierry Lecomte, François Ghiringhell
Journal of Clinical Oncology.2022; 40(3): 262. CrossRef - Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score
Yuji Shimizu, Ryo Ashida, Teiichi Sugiura, Yukiyasu Okamura, Katsuhisa Ohgi, Mihoko Yamada, Shimpei Otsuka, Takeshi Aramaki, Akifumi Notsu, Katsuhiko Uesaka
Annals of Surgical Oncology.2022; 29(9): 5447. CrossRef - Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study
Liu-Fang Ye, Chao Ren, Long Bai, Jie-Ying Liang, Ming-Tao Hu, Hui Yang, Zhi-Qiang Wang, Feng-Hua Wang, Rui-Hua Xu, Yu-Hong Li, De-Shen Wang
Investigational New Drugs.2021; 39(3): 836. CrossRef - Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review
Changhoon Yoo, Sang Hyun Shin, Joon-Oh Park, Kyu-Pyo Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Woohyung Lee, Ki-Byung Song, Dae-Wook Hwang, Jin-hong Park, Jae Hoon Lee
Cancers.2021; 13(7): 1647. CrossRef - Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis
Alexander A. Azizi, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle
Critical Reviews in Oncology/Hematology.2021; 163: 103328. CrossRef - Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study
Lu Zou, Xuechuan Li, Xiangsong Wu, Jiujie Cui, Xuya Cui, Xiaoling Song, Tai Ren, Xusheng Han, Yidi Zhu, Huaifeng Li, Wenguang Wu, Xu’an Wang, Wei Gong, Liwei Wang, Maolan Li, Wan Yee Lau, Yingbin Liu
BMC Cancer.2021;[Epub] CrossRef - A Novel Combination of Bevacizumab with Chemotherapy Improves Therapeutic Effects for Advanced Biliary Tract Cancer: A Retrospective, Observational Study
Sung-Nan Pei, Chun-Kai Liao, Yaw-Sen Chen, Cheng-Hao Tseng, Chao-Ming Hung, Chong-Chi Chiu, Meng-Che Hsieh, Yu-Fen Tsai, Hsiu-Yun Liao, Wei-Ching Liu, Kun-Ming Rau
Cancers.2021; 13(15): 3831. CrossRef - Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Ilhwan Kim, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K Abou-Alfa, Baek-Yeol Ryoo
The Lancet Oncology.2021; 22(11): 1560. CrossRef - Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial
Ali Belkouz, Judith de Vos-Geelen, Ron A. A. Mathôt, Ferry A. L. M. Eskens, Thomas M. van Gulik, Martijn G. H. van Oijen, Cornelis J. A. Punt, Johanna W. Wilmink, Heinz-Josef Klümpen
British Journal of Cancer.2020; 122(5): 634. CrossRef - miR‐373 inhibits autophagy and further promotes apoptosis of cholangiocarcinoma cells by targeting ULK1
Pin Lv, Yi‐Fan Luo, Wen‐Yi Zhou, Ben Liu, Zheng Zhou, Yong‐Zhong Shi, Ren Huang, Chuang Peng, Zi‐Li He, Jun Wang, Hong‐Hui Zhang, Sheng‐Dan Nie
The Kaohsiung Journal of Medical Sciences.2020; 36(6): 429. CrossRef - Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials
A. Belkouz, J.W. Wilmink, N. Haj Mohammad, J. Hagendoorn, J. de Vos-Geelen, C.H.C. Dejong, M.Y.V. Homs, B. Groot Koerkamp, T.M. van Gulik, M.G.H. van Oijen, C.J.A. Punt, H. Klümpen
Critical Reviews in Oncology/Hematology.2020; 151: 102975. CrossRef - A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer
Ayhan Ulusakarya, Abdoulaye Karaboué, Oriana Ciacio, Gabriella Pittau, Mazen Haydar, Pamela Biondani, Yusuf Gumus, Amale Chebib, Wathek Almohamad, Pasquale F. Innominato
BMC Cancer.2020;[Epub] CrossRef - Overview of current targeted therapy in gallbladder cancer
Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef - Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study
Keke Nie, Ling Zhang, Yunhong You, Hongmei Li, Xiuhui Guo, Zhongfa Zhang, Chunling Zhang, Youxin Ji
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef - The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review
Ming-Liang Wang, Zhang-Yan Ke, Shuai Yin, Chen-Hai Liu, Qiang Huang
Hepatobiliary & Pancreatic Diseases International.2019; 18(2): 110. CrossRef - Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study
L. Perkhofer, A. W. Berger, A. K. Beutel, E. Gallmeier, S. Angermeier, L. Fischer von Weikersthal, T. O. Goetze, R. Muche, T. Seufferlein, T. J. Ettrich
BMC Cancer.2019;[Epub] CrossRef
- A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study
- 10,225 View
- 322 Download
- 21 Web of Science
- 21 Crossref
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