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1.
Sung‐Hyun Hwang Myung‐Chul Kim Sumin Ji Yeseul Yang Yeji Jeong Yongbaek Kim 《Cancer science》2019,110(4):1256-1267
Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy. 相似文献
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Sarina A. Piha-Paul Do-Youn Oh Makoto Ueno David Malka Hyun Cheol Chung Adnan Nagrial Robin K. Kelley Willeke Ros Antoine Italiano Kazuhiko Nakagawa Hope S. Rugo Filippo de Braud Andrea Iolanda Varga Aaron Hansen Hui Wang Suba Krishnan Kevin G. Norwood Toshihiko Doi 《International journal of cancer. Journal international du cancer》2020,147(8):2190-2198
We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity. 相似文献
4.
Hyun Jong Choi Jong Ho Moon Yun Nah Lee Hyun Su Kim Ji Su Ha Tae Hoon Lee Sang‐Woo Cha Young Deok Cho Sang‐Heum Park 《Digestive endoscopy》2015,27(7):772-775
Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS. 相似文献
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Seyed Mehdi BagheriMofidi Majid Pouladian Seyed Behnamedin Jameie Ali Abbaspour Tehrani-Fard 《Australasian physical & engineering sciences in medicine / supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine》2016,39(3):717-726
Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm3. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation. 相似文献
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Kim Dae Woo Kim Yong Min Min Jin-Young Kim Jeong-Whun Kim Jin-Kook Mo Ji-Hun Shin Jae-Min Cho Kyu-Sup Kwak Sang Gyu Shin Seung-Heon 《European archives of oto-rhino-laryngology》2020,277(3):761-765
European Archives of Oto-Rhino-Laryngology - Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of... 相似文献
10.
Li Bai Saeha Shin Richard T. Burnett Jeffrey C. Kwong Perry Hystad Aaron van Donkelaar Mark S. Goldberg Eric Lavigne Scott Weichenthal Randall V. Martin Ray Copes Alexander Kopp Hong Chen 《International journal of cancer. Journal international du cancer》2020,146(9):2450-2459
Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2) and ozone (O3). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM2.5, NO2, O3 and redox-weighted average of NO2 and O3 (Ox) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m3) and NO2 (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox. Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer. 相似文献