Establishment and characterization of a new malignant peritoneal mesothelioma cell line, KOG-1, from the ascitic fluid of a patient with pemetrexed chemotherapy resistance.


  • 影响因子:2.15
  • DOI:10.1007/s13577-019-00286-w
  • 作者列表:"Akahane T","Hirasawa A","Imoto I","Okubo A","Itoh M","Nanki Y","Yoshihama T","Tominaga E","Aoki D
  • 发表时间:2020-01-01

:Malignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time was 13.7 h. Karyotypic and molecular genetic analyses showed that chromosome numbers ranged from 62 to 142, with a peak of 73 with complicated copy number alterations. No germline BAP1 pathogenic variant was detected. Cells expressed various tumor markers of mesothelioma, such as calretinin, podoplanin, and Wilms tumor 1 (WT-1). Drug sensitivity and resistance testing with a set of 36 drugs using 2D and three-dimensional (3D) culture models demonstrated that KOG-1 cells showed high and low sensitivity to pemetrexed under 2D and 3D culture conditions, respectively, whereas control ovarian cancer cell lines showed low sensitivity to pemetrexed under both culture conditions. This newly established cell line will be a valuable biological resource to expand the feasibility of functional studies as well as drug testing for potential therapeutic purposes in MPeM.


: 恶性腹膜间皮瘤 (MPeM) 是一种罕见的侵袭性恶性间皮瘤。用于研究这种癌症的功能特征的足够的生物工具尚未开发。因此,在本研究中,从一名39岁日本女性的腹水中分离出一种新的人癌细胞系KOG-1,该患者具有培美曲塞耐药性MPeM。细胞在解冻后立即呈树突状或线状,在生长过程中表现出拼图状和纺锤体排列,并且在二维 (2D) 培养中形成单层而没有接触抑制。群体倍增时间为13.7 h。染色体核型和分子遗传学分析显示,染色体数目为62-142,峰值为73,拷贝数改变复杂。未检测到种系BAP1致病变异。细胞表达间皮瘤的各种肿瘤标志物,如calretinin、podoplanin和Wilms tumor 1 (WT-1)。使用2D和3D (3D) 培养模型的一组36种药物的药物敏感性和耐药性测试表明,在2D和3D培养条件下,KOG-1细胞分别对培美曲塞显示出高敏感性和低敏感性,而对照卵巢癌细胞系在两种培养条件下对培美曲塞显示出低敏感性。这种新建立的细胞系将是一种有价值的生物资源,用于扩展MPeM中功能研究以及用于潜在治疗目的的药物测试的可行性。



作者列表:["Letica-Kriegel AS","Leinwand JC","Sonett JR","Gorenstein LA","Taub RN","Chabot JA","Kluger MD"]

METHODS:BACKGROUND:The most common sites of malignant mesothelioma are the pleura and peritoneum, but little is known about the incidence, prognosis, or treatment of patients with disease in both cavities. Previous series suggest that multimodality treatment improves overall survival for pleural or peritoneal disease, but studies typically exclude patients with disease in both cavities. Despite limitations, this investigation is the only study to broadly examine outcomes for patients with malignant mesothelioma in both the pleural and peritoneal cavities. METHODS:This study retrospectively examined 50 patients with both pleural and peritoneal mesothelioma treated with the intent to prolong survival. The primary end point was overall survival from the initial operative intervention. RESULTS:The median overall survival was 33.9 months from the initial intervention. Female gender and intraperitoneal dwell chemotherapy were independent predictors of overall survival. Within 1 year after the initial diagnosis, second-cavity disease was diagnosed in 52% of the patients. The median time to the second-cavity diagnosis for those with a diagnosis 1 year after the initial diagnosis was 30 months. CONCLUSIONS:Well-selected patients with both pleural and peritoneal mesothelioma have a survival benefit over palliative treatment that is comparable with that seen in single-cavity disease. The presence of disease in both cavities is not a contraindication to multimodality treatment aimed at prolonging survival, whether the disease is diagnosed synchronously or metachronously. Patients with an initial diagnosis of single cavity disease are at the highest risk for identification of second-cavity disease within the first year after diagnosis.

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作者列表:["Ali YM","Sweeney J","Shen P","Votanopoulos KI","McQuellon R","Duckworth K","Perry KC","Russell G","Levine EA"]

METHODS:INTRODUCTION:Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted treatment for peritoneal mesothelioma. In this study, we evaluated QOL after HIPEC for peritoneal mesothelioma. METHODS:This was a prospective study performed after HIPEC for peritoneal mesothelioma between 2002 and 2015. Patients completed QOL surveys, including the Short Form-36 (SF-36), Functional Assessment of Cancer Therapy + Colon (FACT-C), Brief Pain Inventory (BPI), and Center for Epidemiologic Studies Depression Scale (CES-D) preoperatively and at 3, 6, 12, and 24 months postoperatively. RESULTS:Overall, 46 patients underwent HIPEC for peritoneal mesothelioma and completed QOL surveys. Mean age was 52.8 ± 13.8 years and 52% were male. Good preoperative functional status was 70%. Median survival was 3.4 years, and 1, 3, and 5-year survivals were 77.4, 55.2, and 36.5%, respectively. CES-D score decreased at 3 months postoperatively, but increased at 24 months (p = 0.014); SF-36 physical functioning scale decreased at 3 months but returned to baseline at 12 months (p = 0.0045); and the general health scale decreased at 3 months, then improved by 6 months (p = 0.0034). Emotional well-being (p = 0.0051), role limitations due to emotional problems (p = 0.0006), social functioning (p = 0.0022), BPI (p = 0.025), least pain (p = 0.045), and worst pain (p < 0.0001) improved. FACT-C physical well-being decreased at 3 months but returned to baseline at 6 months (p = 0.020), and total FACT-C score improved at 6 months (p = 0.052). CONCLUSION:QOL returned to baseline or improved from baseline between 3 months and 1 year following surgery. Despite the risks associated with this operation, patients may tolerate HIPEC well and have good overall QOL postoperatively.

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作者列表:["Bayat Z","Taylor EL","Bischof DA","McCart JA","Govindarajan A"]

METHODS:BACKGROUND:Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be associated with decreases in quality of life (QOL). Bowel-related QOL (BR-QOL) after CRS-HIPEC has not been previously studied. The objectives of the current study were to examine the effect of different types of bowel resection during CRS-HIPEC on overall QOL and BR-QOL. METHODS:A prospective cohort study was performed. QOL data were collected using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR-29 questionnaires at 3, 6, and 12 months after CRS-HIPEC. Patients were divided into groups that underwent no bowel resection, non-low anterior resection (LAR) bowel resection, LAR, and LAR with stoma. Primary outcomes were global QOL and BR-QOL. RESULTS:Overall, 158 patients were included in this study. Bowel resections were performed in 77% of patients, with 31% undergoing LAR. Global QOL was not significantly different between groups. LAR patients (with and without stoma) had significantly worse BR-QOL, embarrassment, and altered body image, with LAR + stoma patients having the largest impairments in these domains. Trends toward higher levels of impotence and anxiety were also seen in LAR patients. Although global QOL improved over time, impairments in BR-QOL and sexual and social function did not significantly improve over time. CONCLUSIONS:Although global QOL after CRS-HIPEC was not affected by the type of bowel resection, the use of LAR and ostomies was associated with clinically meaningful and persistent impairments in BR-QOL and related functional domains. Generic QOL questionnaires may not adequately capture these domains; however, targeted questionnaires in these patients may help improve QOL after CRS-HIPEC.

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