Journal of Chemotherapy最新文献

{"title":"A comparative study of ceftazidime/avibactam-based and fosfomycin plus meropenem-based regimens for managing infections caused by carbapenem-resistant <i>Klebsiella pneumoniae</i> in critically ill patients.","authors":"Uğur Önal, Ülkü Tüzemen, Pınar Küçükdemirci Kaya, Remzi İşçimen, Nermin Kelebek Girgin, Cüneyt Özakın, Ferda Kahveci, Halis Akalın","doi":"10.1080/1120009X.2024.2349439","DOIUrl":"https://doi.org/10.1080/1120009X.2024.2349439","url":null,"abstract":"<p><p>The main aim of this study was to compare and analyze the effectiveness of treatment regimens using ceftazidime/avibactam (CAZ/AVI) versus fosfomycin plus meropenem (FOS/MER) for managing bloodstream infections (BSI) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) in critically ill patients. Between 4 January 2019, and 16 July 2023, adult patients (≥18 years old) diagnosed with BSI or VAP due to culture confirmed CRKP in ICU of a tertiary care hospital were investigated retrospectively. A total of 71 patients were categorized into two groups: 30 patients in CAZ/AVI-based, and 41 patients in FOS/MER-based group. No substantial disparities were found in the total duration of ICU hospitalization, as well as the 14- and 30-day mortality rates, between patients treated with CAZ/AVI-based and FOS/MER-based therapeutic regimens. We consider that our study provides for the first time a comprehensive understanding of treatment outcomes and associated risk factors among patients with CRKP-related infections.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862904","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":"Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.","authors":"Noriaki Kataoka, Takeo Hata, Kouichi Hosomi, Atsushi Hirata, Satoe Fujiwara, Emi Goto, Masami Nishihara, Masahide Ohmichi, Masashi Neo","doi":"10.1080/1120009X.2024.2345025","DOIUrl":"https://doi.org/10.1080/1120009X.2024.2345025","url":null,"abstract":"<p><p>We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-7"},"PeriodicalIF":1.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849336","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":"CircAGFG1 absence decreases PKM2 expression to enhance oxaliplatin sensitivity in colorectal cancer in a miR-7-5p-dependent manner.","authors":"Jun Chen, Hongwei Wang, Mingsheng Tang","doi":"10.1080/1120009X.2023.2253680","DOIUrl":"10.1080/1120009X.2023.2253680","url":null,"abstract":"<p><p>Circular RNA (circRNA) ArfGAP with FG repeats 1 (circAGFG1) contributes to colorectal cancer (CRC) development. However, whether circAGFG1 regulates the resistance of CRC to oxaliplatin (L-OHP) remains unknown. CircAGFG1, microRNA-7-5p (miR-7-5p) and pyruvate kinase M2 (PKM2) RNA expression were quantified by quantitative real-time polymerase chain reaction. Protein expression was detected by western blot assay and immunohistochemistry assay. Glycolysis was analyzed through glucose uptake, lactate production and adenosine triphosphate (ATP) concentration assays. 50% inhibitory concentration of L-OHP was determined by cell counting kit-8 assay. Cell proliferation and apoptotic rate were analyzed by cell colony formation and flow cytometry analysis, respectively. Dual-luciferase reporter assay was used to identify the relationship among circAGFG1, miR-7- 5p and PKM2. The effect of circAGFG1 on L-OHP sensitivity <i>in vivo</i> was further evaluated by a xenograft model assay. CircAGFG1 and PKM2 expression were significantly increased, while miR-7-5p was decreased in L-OHP-resistant CRC tissues and cells. High circAGFG1 expression predicted a poor prognosis of CRC. CircAGFG1 knockdown or PKM2 depletion decreased glycolysis and cell proliferation and increased L-OHP sensitivity and cell apoptosis. PKM2 introduction rescued circAGFG1 silencing-induced effects in CRC cells. In terms of mechanism, circAGFG1 bound to miR-7-5p, which was identified to target PKM2. Also, circAGFG1 regulated PKM2 expression by interacting with miR-7-5p. Further, circAGFG1 knockdown improved the sensitivity of tumors to L-OHP <i>in vivo</i>. CircAGFG1 depletion inhibited L-OHP resistance by regulating the miR-7-5p/PKM2 pathway.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"208-221"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205416","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":"Enhanced synergy of pacritinib with temsirolimus and sunitinib in preclinical renal cell carcinoma model by targeting JAK2/STAT pathway.","authors":"Fei Mao, Liangkui Gao, Liming Liu, Yuanjia Tang","doi":"10.1080/1120009X.2023.2274700","DOIUrl":"10.1080/1120009X.2023.2274700","url":null,"abstract":"<p><p>Pacritinib is an oral medication that inhibits several kinases including JAK2, FLT3, IRAK and STAT3. It has been recently approved to treat patients with thrombocytopenia and myelofibrosis. Studies are currently exploring the potential use of pacritinib in treating other types of cancer such as leukaemia, breast cancer and prostate cancer. Our study aimed to investigate the effects of pacritinib alone and its combination with standard of care in renal cell carcinoma (RCC). We showed that pacritinib dose-dependently decreased viability of RCC cells, with IC₅₀ at nanomolar or low micromolar concentration rage. Pacritinib inhibited cell proliferation, decreased colony formation, and increased apoptosis. Interestingly, pacritinib exhibited synergistic effects when combined with temsirolimus and sunitinib, but antagonistic effects when combined with doxorubicin, in a panel of RCC cell lines. We also confirmed that the combination of pacritinib with temsirolimus and sunitinib resulted in synergistic effects in RCC mouse models, with complete inhibition of tumour growth throughout the treatment period. Mechanistic studies indicated that the inhibition of JAK2, but not IRAK, was the main contributor to the anti-RCC activity of pacritinib. Our study is the first to demonstrate that pacritinib shows promise as a treatment option for RCC and underscores the therapeutic potential of targeting the JAK2/STAT signalling pathway in RCC.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"238-248"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71424017","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":"Astaxanthin induces autophagy and apoptosis in murine melanoma B16F10-Nex2 cells and exhibits antitumor activity <i>in vivo</i>.","authors":"Fernanda Fernandes Miranda da Cunha, Angela Pedroso Tonon, Fabricio Machado, Luis Rodolpho Travassos, Nathalia Grazzia, João Fernando Possatto, Agnes Kobayashi Calvo de Sant'ana, Rayssa de Mello Lopes, Tiago Rodrigues, Danilo Ciccone Miguel, Fernanda Ramos Gadelha, Denise Costa Arruda","doi":"10.1080/1120009X.2023.2264585","DOIUrl":"10.1080/1120009X.2023.2264585","url":null,"abstract":"<p><p>Countless efforts have been made to prevent and suppress the formation and spread of melanoma. Natural astaxanthin (AST; extracted from the alga <i>Haematococcus pluvialis</i>) showed an antitumor effect on various cancer cell lines due to its interaction with the cell membrane. This study aimed to characterize the antitumor effect of AST against B16F10-Nex2 murine melanoma cells using cell viability assay and evaluate its mechanism of action using electron microscopy, western blotting analysis, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and mitochondrial membrane potential determination. Astaxanthin exhibited a significant cytotoxic effect in murine melanoma cells with features of apoptosis and autophagy. Astaxanthin also decreased cell migration and invasion <i>in vitro</i> assays at subtoxic concentrations. In addition, assays were conducted in metastatic cancer models in mice where AST significantly decreased the development of pulmonary nodules. In conclusion, AST has cytotoxic effect in melanoma cells and inhibits cell migration and invasion, indicating a promising use in cancer treatment.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"222-237"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101710","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":"Correction.","authors":"","doi":"10.1080/1120009X.2023.2276538","DOIUrl":"10.1080/1120009X.2023.2276538","url":null,"abstract":"","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":"36 3","pages":"264-265"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849822","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":"Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.","authors":"Aslı Özden, Büşra Dalgıç, Mervenur Demir, Gülşen Hazırolan, Ömrüm Uzun, Gökhan Metan","doi":"10.1080/1120009X.2023.2296146","DOIUrl":"10.1080/1120009X.2023.2296146","url":null,"abstract":"&lt;p&gt;&lt;p&gt;It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"190-197"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829899","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":"Varicella zoster virus reactivation reported with isatuximab use.","authors":"Michelle Nadeau Nguyen, Graça M Dores, Afrouz Nayernama, S Christopher Jones","doi":"10.1080/1120009X.2023.2266201","DOIUrl":"10.1080/1120009X.2023.2266201","url":null,"abstract":"<p><p>Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (<i>n</i> = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"198-201"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41131148","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":"Combined impact of hypoalbuminemia and pharmacogenomic variants on voriconazole trough concentration: data from a real-life clinical setting in the Chinese population.","authors":"Yuanyuan Li, Ying Zhang, Jinxia Zhao, Jialu Bian, Yinyu Zhao, Xu Hao, Boyu Liu, Lei Hu, Fang Liu, Changqing Yang, Yufei Feng, Lin Huang","doi":"10.1080/1120009X.2023.2247208","DOIUrl":"10.1080/1120009X.2023.2247208","url":null,"abstract":"<p><p>Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (C_min) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of <i>CYP2C19</i>, <i>CYP3A4</i>, <i>CYP3A5</i>, <i>CYP2C9</i>, <i>FMO3</i>, <i>ABCB1</i>, <i>POR</i>, <i>NR1I2</i> and <i>NR1I3</i> were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC C_min adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (<i>R</i>² = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) <i>CYP2C19</i> genotype and CRP level (<i>R²</i> = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"179-189"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028986","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":"Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy.","authors":"Kadriye Bir Yücel, Atiye Cenay Karabörk Kilic, Osman Sütcüoglu, Ozan Yazıcı, Koray Kilic, Gözde Savaş, Aytug Uner, Nazan Günel, Ahmet Özet, Nuriye Özdemir","doi":"10.1080/1120009X.2023.2246786","DOIUrl":"10.1080/1120009X.2023.2246786","url":null,"abstract":"<p><p>The aim of our study was to evaluate the association between increased splenic volume (SV) and liver fibrosis indices in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Patients who received adjuvant oxaliplatin-based regimens with the diagnosis of stage II and III colon cancer were evaluated. Splenic volume measurements, liver function tests, platelet count, and non-invasive liver fibrosis indices [NAFLD fibrosis score (NFS), AST to platelet ratio (APRI), and Fibrosis-4 (FIB-4)] were measured before and after treatment. A 30% increase in SV after chemotherapy compared to baseline was considered increased SV. The rate of increase in SV was 57.7% in the whole group. An increase in SV was shown at a higher rate in patients treated with capecitabine and oxaliplatin (CAPOX) than those treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (66.3% vs. 36.8%, <i>p</i> = 0.002). Furthermore, the CAPOX regimen (OR: 2.831, 95% CI: 1.125-7.121; <i>p</i> = 0.027), and higher post-treatment FIB-4 score (OR: 3.779; 95% CI:1.537- 9.294, <i>p</i> = 0.004) were determined as independent risk factors for the increased SV. Our study revealed that increased SV had a significant association with higher FIB-4 score in patients treated with oxaliplatin-based chemotherapy.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"249-257"},"PeriodicalIF":1.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362734","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}