Cancer Research and Treatment

Original Articles

General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

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Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

Citations to this article as recorded by

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
Cell Reports Medicine.2024; 5(3): 101461. CrossRef
Establishment and Advancement of Pancreatic Organoids
Dong Hyeon Lee
Keimyung Medical Journal.2024; 43(1): 3. CrossRef
Organoid as a promising tool for primary liver cancer research: a comprehensive review
Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
Cell & Bioscience.2024;[Epub] CrossRef
The use of organoids in creating immune microenvironments and treating gynecological tumors
Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
Journal of Translational Medicine.2024;[Epub] CrossRef
Organoid: Bridging the gap between basic research and clinical practice
Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
Cancer Letters.2023; 572: 216353. CrossRef

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Gastrointestinal cancer

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma: Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1303-1312. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.291

Abstract PDF Supplementary Material PubReader ePub

Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Citations

Citations to this article as recorded by

MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C
Wen-Jing Liu, Jun Lu, Wei-Xun Zhou, Jian-Zhou Liu, Li Zhou
Laboratory Investigation.2024; 104(9): 102107. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
Laboratory Medicine Online.2024; 14(4): 311. CrossRef
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
Antonino Pantaleo, Giovanna Forte, Candida Fasano, Martina Lepore Signorile, Paola Sanese, Katia De Marco, Elisabetta Di Nicola, Marialaura Latrofa, Valentina Grossi, Vittoria Disciglio, Cristiano Simone
Cancers.2023; 16(1): 56. CrossRef

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Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study: Sang Myung Woo, Min Kyeong Kim, Jungnam Joo, Kyong-Ah Yoon, Boram Park, Sang-Jae Park, Sung-Sik Han, Ju Hee Lee, Eun Kyung Hong, Yun-Hee Kim, Hae Moon, Sun-Young Kong, Tae Hyun Kim, Woo Jin Lee; Cancer Res Treat. 2017;49(4):1022-1032. Published online January 19, 2017; DOI: https://doi.org/10.4143/crt.2016.495

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
Materials and Methods
In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
Results
Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
Conclusion
Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

Citations

Citations to this article as recorded by

Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma
Krishan R. Jethwa, Ed Kim, Jordan Berlin, Christopher J. Anker, Leila Tchelebi, Gerard Abood, Christopher L. Hallemeier, Salma Jabbour, Timothy Kennedy, Rachit Kumar, Percy Lee, Navesh Sharma, William Small, Vonetta Williams, Suzanne Russo
American Journal of Clinical Oncology.2024; 47(4): 185. CrossRef
Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer
Y. Li, J. Wu, Y. Feng, D. Wang, H. Tao, J. Wen, F. Jiang, P. Qian, Y. Liu
Cancer/Radiothérapie.2024; 28(3): 242. CrossRef
Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?
Olivier Caliez, Daniel Pietrasz, Feryel Ksontini, Solène Doat, Jean-Marc Simon, Jean-Christophe Vaillant, Valerie Taly, Pierre Laurent-Puig, Jean-Baptiste Bachet
Digestive and Liver Disease.2022; 54(10): 1428. CrossRef
Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review
Marisol Huerta, Susana Roselló, Luis Sabater, Ana Ferrer, Noelia Tarazona, Desamparados Roda, Valentina Gambardella, Clara Alfaro-Cervelló, Marina Garcés-Albir, Andrés Cervantes, Maider Ibarrola-Villava
Cancers.2021; 13(5): 994. CrossRef
Clinical Utility of Liquid Biopsy-Based Actionable Mutations Detected via ddPCR
Irina Palacín-Aliana, Noemí García-Romero, Adrià Asensi-Puig, Josefa Carrión-Navarro, Víctor González-Rumayor, Ángel Ayuso-Sacido
Biomedicines.2021; 9(8): 906. CrossRef
A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers
Sheng-Nan Jia, Fu-Xing Wen, Ting-Ting Gong, Xin Li, Hui-Jie Wang, Ya-Min Sun, Ze-Cheng Yang
International Journal of Radiation Biology.2020; 96(3): 383. CrossRef
Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer
Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo, Eun Sang Oh, Sang Hee Youn, Hye Young Jang, Sung-Sik Han, Sang-Jae Park, Yang-Gun Suh, Sung Ho Moon, Sang Soo Kim, Dae Yong Kim
Scientific Reports.2020;[Epub] CrossRef
Comprehensive Cancer Panel Sequencing Defines Genetic Diversity and Changes in the Mutational Characteristics of Pancreatic Cancer Patients Receiving Neoadjuvant Treatment
Kyong-Ah Yoon, Sang Myung Woo, Yun-Hee Kim, Sun-Young Kong, Min Kyoung Lee, Sung-Sik Han, Tae Hyun Kim, Woo Jin Lee, Sang-Jae Park
Gut and Liver.2019; 13(6): 683. CrossRef
Plasma Cell-Free DNA as a Predictive Marker after Radiotherapy for Hepatocellular Carcinoma
Sangjoon Park, Eun Jung Lee, Chai Hong Rim, Jinsil Seong
Yonsei Medical Journal.2018; 59(4): 470. CrossRef
Effectiveness and Safety of Simultaneous Integrated Boost-Proton Beam Therapy for Localized Pancreatic Cancer
Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo, Hyunjung Kim, Eun Sang Oh, Ju Hee Lee, Sung-Sik Han, Sang-Jae Park, Yang-Gun Suh, Sung Ho Moon, Sang Soo Kim, Dae Yong Kim
Technology in Cancer Research & Treatment.2018;[Epub] CrossRef

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