Journal of Chemotherapy最新文献

{"title":"MHY446 induces apoptosis via reactive oxygen species-mediated endoplasmic reticulum stress in HCT116 human colorectal cancer cells.","authors":"Yu Ra Ahn, Jung Yoon Jang, Yong Jung Kang, Hye Jin Oh, Min Kyung Kang, Dahye Yoon, Hyung Sik Kim, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim","doi":"10.1080/1120009X.2023.2286757","DOIUrl":"10.1080/1120009X.2023.2286757","url":null,"abstract":"<p><p>This study investigated the potential of a newly synthesized histone deacetylase (HDAC) inhibitor, MHY446, in inducing cell death in HCT116 colorectal cancer cells and compared its activity with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. The results showed that MHY446 increased the acetylation of histones H3 and H4 and decreased the expression and activity of HDAC proteins in HCT116 cells. Additionally, MHY446 was confirmed to bind more strongly to HDAC1 than HDAC2 and inhibit its activity. <i>In vivo</i> experiments using nude mice revealed that MHY446 was as effective as SAHA in inhibiting HCT116 cell-grafted tumor growth. This study also evaluated the biological effects of MHY446 on cell survival and death pathways. The reactive oxygen species (ROS) scavenger <i>N</i>-acetyl-L-cysteine (NAC) confirmed that ROS play a role in MHY446-induced cell death by reducing poly(ADP-ribose) polymerase cleavage. MHY446 also induced cell death <i>via</i> endoplasmic reticulum (ER) stress by increasing the expression of ER stress-related proteins. NAC treatment decreased the expression of ER stress-related proteins, indicating that ROS mediate ER stress as an upstream signaling pathway and induce cell death. While MHY446 did not exhibit superior HDAC inhibition efficacy compared to SAHA, it is anticipated to provide innovative insights into the future development of therapeutic agents for human CRC by offering novel chemical structure-activity relationship-related information.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"483-500"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of veliparib in the treatment of advanced/metastatic breast cancer: a meta-analysis of phase II and III randomized controlled trials.","authors":"Wenxia Sun, Jing Li","doi":"10.1080/1120009X.2023.2281760","DOIUrl":"10.1080/1120009X.2023.2281760","url":null,"abstract":"<p><p>We conducted a meta-analysis to evaluate the efficacy and safety of veliparib in the treatment of advanced/metastatic breast cancer. Databases were searched for relevant studies till June 2023. Six RCTs involving 1912 patients were included. The pooled analysis provided evidence that veliparib-containing regimens could significantly improve the PFS (HR: 0.71; 95% CI: 0.61-0.83; <i>p</i> < 0.0001), OS (HR: 0.87; 95% CI: 0.76-0.99; <i>p</i> = 0.03), and ORR (RR: 1.52; 95% CI:1.06-2.18; <i>p</i> = 0.02) than those of controls for treating advanced/metastatic breast cancer. Breast cancer patients with <i>BRCA</i>-mutation tended to have a better PFS than the <i>BRCA</i>-wildtype group, and patients with TNBC tended to associated with a longer PFS than the non-TNBC group. Veliparib could significantly increase the risk of anemia, leukopenia, neutropenia, diarrhea, stomatitis, fatigue, and peripheral neuropathy. Anemia and neutropenia should be well concerned. The veliparib-containing regimen was efficacious in treating advanced/metastatic breast cancer with a controllable safety factor.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"441-448"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in MUC1 resistance to chemotherapy in pancreatic cancer.","authors":"Youhao Yao, Daguang Fan","doi":"10.1080/1120009X.2023.2282839","DOIUrl":"10.1080/1120009X.2023.2282839","url":null,"abstract":"<p><p>The incidence of pancreatic cancer (PC), a highly fatal malignancy, is increasing every year. Chemotherapy is an important treatment for it in addition to surgery, yet most patients become resistant to chemotherapeutic agents within a few weeks of treatment initiation.​ MUC1 is a highly glycosylated transmembrane protein, and studies have shown that aberrantly glycosylated overexpression of MUC1 is involved in regulating the biology of chemoresistance in cancer cells. This article summarizes the mechanism of MUC1 in PC chemoresistance and reviews MUC1-based targeted therapies.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"449-456"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of in vitro activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against MRSA isolates: a two center study.","authors":"Hasan Cenk Mirza, Özlem Öğüç Şanlı","doi":"10.1080/1120009X.2024.2316539","DOIUrl":"10.1080/1120009X.2024.2316539","url":null,"abstract":"<p><p>There is an increasing need for new synergistic antimicrobial combinations against multidrug-resistant bacteria. Our objective was to evaluate the activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) isolates recovered at two centers in Turkey. Activities of ceftaroline and ceftobiprole were tested against 100 MRSA isolates using gradient diffusion method. Activities of ceftaroline and ceftobiprole in combination with trimethoprim/sulfamethoxazole against 20 selected isolates (including all isolates that were non-susceptible to ceftaroline or ceftobiprole, and randomly selected isolates) were investigated using MIC:MIC ratio method. Antimicrobial interactions were interpreted using the fractional inhibitory concentration (FIC) index. The MIC₅₀/MIC₉₀ values for ceftaroline and ceftobiprole were 0.75/1 and 1/1.5 mg/L, respectively. Ceftaroline and ceftobiprole susceptibility rates among 100 MRSA isolates were 94% and 96%, respectively. Ceftaroline, ceftobiprole and trimethoprim/sulfamethoxazole MICs of isolates were not increased when ceftaroline or ceftobiprole was combined with trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination demonstrated additivity against 35%, whereas ceftaroline- trimethoprim/sulfamethoxazole combination demonstrated additivity against 10% of 20 MRSA isolates. The remaining interactions for MRSA isolates were indifference. Three (75%) of four ceftobiprole-resistant isolates became susceptible to ceftobiprole after adding trimethoprim/sulfamethoxazole. None of the ceftaroline non-susceptible isolates became susceptible to ceftaroline after adding trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination may be a better treatment option than ceftaroline- trimethoprim/sulfamethoxazole combination for MRSA infections. Clinical studies are needed to confirm the results of our <i>in vitro</i> study.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"457-464"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraperitoneal daptomycin dosing for peritonitis may be inadequate: a Monte Carlo simulation approach to optimize dosing and outcomes.","authors":"Taniya Charoensareerat, Tipvilai Taweepunturat, Vipavee Rodjun, Dhakrit Rungkitwattanakul, Sutthiporn Pattharachayakul, Aroonrut Lucksiri, Chonnikan Chutkrailert, Kittiwan Suksawat, Surisara Phasaprated, Susan J Lewis, Weerachai Chaijamorn","doi":"10.1080/1120009X.2024.2407705","DOIUrl":"https://doi.org/10.1080/1120009X.2024.2407705","url":null,"abstract":"<p><p>A two-compartmental mathematical pharmacokinetic model with first-order elimination of patients receiving CAPD of 4 exchanges for 6 h with 2 L of dialysate used in each cycle was developed to predict daptomycin disposition in 120 h of therapy. The pharmacodynamic target was plasma AUC/MIC equal to or greater than 666. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Administering intraperitoneal 300 mg daily for 1 exchange daily regimen would be sufficient to treat peritonitis with <i>S. aureus</i> infection with MICs of 0.25 mg/L in patients undergoing CAPD. A higher dosage may be required for infections with a higher minimum inhibitory concentration. Pharmacodynamic targets and MICs significantly contributed to daptomycin doses in this setting. Clinical validation of our recommendations is recommended.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors of poor nutrition in non-small cell lung cancer patients after chemotherapy: cross-sectional study.","authors":"Xiaohan Wang, Xiaodong Qu","doi":"10.1080/1120009X.2024.2403183","DOIUrl":"https://doi.org/10.1080/1120009X.2024.2403183","url":null,"abstract":"<p><p>This cross-sectional study aimed to analyze the associated factors of poor nutrition in non-small cell lung cancer (NSCLC) patients after chemotherapy. Concretely, 176 NSCLC patients who attended our hospital from June 2020 to December 2022 were enrolled. Standard-compliant patients were categorized into nutrition group (<i>n</i> = 38) and malnutrition group (<i>n</i> = 70) according to different nutrition statuses. Baseline characteristics and nutrition level were assessed. Associated factors of poor nutrition were analyzed by logistic regression analysis. There were obvious differences between nutrition group and malnutrition group in terms of age (P = 0.041), body mass index (BMI, <i>p</i> = 0.021), residence (P  = 0.023), per capita monthly income of family (P  = 0.023), tumor staging (P  = 0.017), Karnofsky (KPS) score (P <i> <</i> 0.001), effect of chemotherapy (P  = 0.045), and nutrition support before chemotherapy only (P  = 0.023) and perichemotherapy (P = 0.011). The higher proportion of NSCLC patients was found in malnutrition group relative to nutrition group in terms of having poor nutritional cognition (67.14% vs. 47.37%, P  = 0.045), and lacking access to vitamins (65.71% vs. 44.74%, P  = 0.047) and trace elements (57.14% vs. 36.84%, P  = 0.044). BMI <18.5 (OR = 3.707, P = 0.007, 95%<i>CI</i> (1.434-9.586)), residence in village (OR = 3.426, P = 0.013, 95%<i>CI</i> (1.291-9.092)), and KPS score ≤70 (OR = 7.608, P < 0.001, 95%<i>CI</i> (2.842-20.367)) were associated factors for poor nutrition. Collectively, BMI, residence, and KPS score were associated factors of poor nutrition in NSCLC patients after chemotherapy.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colistin resistance among the Gram-negative nosocomial pathogens in India: a systematic review and meta-analysis.","authors":"Sambit K Dwibedy, Indira Padhy, Aditya K Panda, Saswat S Mohapatra","doi":"10.1080/1120009X.2024.2405355","DOIUrl":"https://doi.org/10.1080/1120009X.2024.2405355","url":null,"abstract":"<p><p>The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. However, the unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (Col^R) bacterial strains. Unfortunately, comprehensive data on the prevalence of Col^R nosocomial pathogens in India are scarce. This study was conducted to address this information gap. A systematic review and meta-analysis were conducted to determine the prevalence of Col^R among the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using a forest plot with a random-effect model. Cochrane Q statistics and <i>I²</i> statistics were used to detect possible heterogeneity. From a total of 1865 retrieved records from 4 databases, 33 studies were included in the study. Among the most common nosocomial pathogens<i>, Klebsiella pneumoniae</i> showed a rate of Col^R at 16.1% (95% CI: 10.1 to 24.6), followed by <i>Pseudomonas aeruginosa</i> (13.3%) (95% CI: 9.1 to 19.2), <i>Acinetobacter baumannii</i> (10%) (95% CI: 7.5 to 13.2), and <i>Escherichia coli</i> (7.8%) (95% CI: 5.3 to 11.2). Interestingly, our analysis revealed that <i>Enterobacter cloacae</i> have the highest rate of Col^R at 27.9% (95% CI: 12.7 to 50.9). The results indicate that the prevalence of Col^R nosocomial pathogens vary among regions and over time; however, continuous monitoring, and sustained efforts are crucial to ensure the effectiveness of colistin antibiotic.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer - a systematic review and meta-analysis.","authors":"Longlan Zhou,Lin Zhang","doi":"10.1080/1120009x.2024.2402175","DOIUrl":"https://doi.org/10.1080/1120009x.2024.2402175","url":null,"abstract":"To assess the association between the timing of postsurgical adjuvant chemotherapy and overall survival (OS) and disease-free survival (DFS) in patients with pancreatic cancer (PC). Literature search of PubMed, EMBASE, and Scopus databases was done for randomized controlled trials (RCTs) or observational studies (cohort studies, case-control studies), reporting outcomes of adult PC patients (aged 18 and above) who underwent surgery and received adjuvant chemotherapy at different time points after the operation. Pooled effect sizes were quantified and reported as hazard ratio (HR). The primary outcomes were OS and DFS. A random effects model to was used account for potential variability across studies. Sixteen studies were included. There was no significant difference between early and delayed initiation of adjuvant chemotherapy in terms of OS (HR 1.03, 95% CI: 0.98, 1.08) and DFS (HR 1.09, 95% CI: 0.91, 1.31). Subgroup analyses based on tumour stage, sample size, and the number of chemotherapeutic agents used did not reveal significant associations. Delayed initiation was associated with reduced OS in patients with well- to moderately differentiated tumours, with the confidence intervals approaching statistical significance (HR 1.12, 95% CI: 1.00,1.25). There was no significant association between the timing of postoperative adjuvant chemotherapy initiation and OS and DFS in patients with pancreatic cancer. These findings underscore the importance of optimizing treatment strategies and suggest that clinicians need to focus on other critical aspects such as drug selection, dosage, and patient-specific factors that might substantially impact treatment efficacy.","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":"29 1","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible chemoresistance of pancreatic cancer grown as spheroids.","authors":"Yoshihisa Matsushita, Alexis Norris, Yi Zhong, Asma Begum, Hong Liang, Marija Debeljak, Nicole Anders, Michael Goggins, Zeshaan A Rasheed, Ralph H Hruban, Christopher L Wolfgang, Elizabeth D Thompson, Michelle A Rudek, Jun O Liu, Leslie Cope, James R Eshleman","doi":"10.1080/1120009X.2024.2402177","DOIUrl":"10.1080/1120009X.2024.2402177","url":null,"abstract":"<p><p>Better <i>in vitro</i> models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling effect, combinations, and clinical applications of triciribine.","authors":"Shinichiro Takahashi","doi":"10.1080/1120009x.2024.2403050","DOIUrl":"https://doi.org/10.1080/1120009x.2024.2403050","url":null,"abstract":"Triciribine (TCN) is a tricyclic nucleoside. Its synthesis was first described in 1971. Subsequent studies have indicated that TCN plays a role in inhibiting DNA synthesis and was revealed to possess a higher selectivity for Akt. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections.","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":"1 1","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}