Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients

副腎腫瘍と鑑別が困難であった肝血管腫の1例

62歳男.原発性副甲状腺機能亢進症及びCTにて偶然発見された腹部腫瘤の精査加療の為当科受診, 超音波断層法, CT, MRIにて4.0×2.5cmの内部不均一な腫瘍を肝と右腎の間に認めた.超音波カラードプラ法では明かな血流を認めず, 副腎機能は正常であった.原発性副甲状腺機能亢進症及び内分泌非活性型副腎腫瘍の診断にて, まず副甲状腺腫瘍摘除術を施行した.その3週間後腹腔鏡的右副腎摘除術を施行した所, 腫瘍は肝より発生しており, 開放的肝部分切除術を施行した.腫瘍は病理組織にて肝海綿状血管腫であったA rare case of exophytic hepatic hemangioma preoperatively diagnosed as a non-functioning adrenal tumor is reported. A 62-year-old man was admitted for treatment of primary hyper-parathyroidism and an incidental adrenal tumor. A 4.0 x 2.5 cm heterogeneous tumor located between the liver and the right kidney was detected by abdominal ultrasonography, computed tomography and magnetic resonance imaging. Color doppler images revealed no apparent blood flow. Since the tumor seemed to have originated from the liver under laparoscopy, an open partial hepatectomy was performed. Histopathological examination revealed cavernous hemangioma of the liver. When diagnosing non-functioning right adrenal tumor, it may be necessary to carefully rule out an exophytic liver tumor

COMBINED CHEMOTHERAPY OF TUBERCULOSIS WITH KANAMYCIN AND CYCLOSERINE : I. THE ANTITUBERCULOUS ACTIVITY OF COMBINED USE OF KANAMYCIN AND CYCLOSERINE IN VITRO AND IN ANIMALS

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました

Absence of viral interference and different susceptibility to interferon between hepatitis B virus and hepatitis C virus in human hepatocyte chimeric mice

Background/Aims: Both hepatitis B virus (HBV) and hepatitis C virus (HCV) replicate in the liver and show resistance against innate immunity and interferon (IFN) treatment. Whether there is interference between these two viruses is still controversial. We investigated the interference between these two viruses and the mode of resistance against IFN. Methods: We performed infection experiments with either or both of the two hepatitis viruses in human hepatocyte chimeric mice. Huh7 cell lines with stable production of HBV were also established and transfected with HCV JFH1 clone. Mice and cell lines were treated with IFN. The viral levels in mice sera and culture supernatants and messenger RNA levels of IFN-stimulated genes were measured. Results: No apparent interference between the two viruses was seen ill vivo. Only a small (0.3 log) reduction in serum HBV and a rapid reduction in HCV were observed after IFN treatment, regardless of infection with the other virus. In ill vitro studies, no interference between the two viruses was observed. The effect of IFN on each virus was not affected by the presence of the other virus. IFN-induced reductions of viruses in culture supernatants were similar to those in ill vivo study. Conclusions: No interference between the two hepatitis viruses exists in the liver in the absence of hepatitis. The mechanisms of IFN resistance of the two viruses target different areas of the IFN system