Chemotherapy最新文献

{"title":"Novel Tetrazoles against Acanthamoeba castellanii Belonging to the T4 Genotype.","authors":"Yassmin Isse Wehelie,&nbsp;Naveed Ahmed Khan,&nbsp;Itrat Fatima,&nbsp;Areeba Anwar,&nbsp;Kanwal Kanwal,&nbsp;Khalid M Khan,&nbsp;Ruqaiyyah Siddiqui,&nbsp;Yuh Koon Tong,&nbsp;Ayaz Anwar","doi":"10.1159/000520585","DOIUrl":"https://doi.org/10.1159/000520585","url":null,"abstract":"<p><strong>Background: </strong>Acanthamoeba castellanii is a pathogenic free-living amoeba responsible for blinding keratitis and fatal granulomatous amoebic encephalitis. However, treatments are not standardized but can involve the use of amidines, biguanides, and azoles.</p><p><strong>Objectives: </strong>The aim of this study was to synthesize a variety of synthetic tetrazole derivatives and test their activities against A. castellanii.</p><p><strong>Methods: </strong>A series of novel tetrazole compounds were synthesized by one-pot method and characterized by NMR and mass spectroscopy. These compounds were subjected to amoebicidal and cytotoxicity assays against A. castellanii belonging to the T4 genotype and human keratinocyte skin cells, respectively. Additionally, reactive oxygen species determination and electron microscopy studies were carried out. Furthermore, two of the seven compounds were conjugated with silver nanoparticles to study their anti-amoebic potential.</p><p><strong>Results: </strong>A series of seven tetrazole derivatives were synthesized successfully. The selected tetrazoles showed anti-amoebic activities at 10 μM concentration against A. castellanii in vitro. The compounds tested caused increased reactive oxygen species generation in A. castellanii and morphological damage to amoebal membranes. Moreover, conjugation of silver nanoparticles enhanced anti-amoebic effects of two tetrazoles.</p><p><strong>Conclusions: </strong>The results showed that azole compounds hold promise in the development of new formulations of anti-Acanthamoebic agents.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"183-192"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39686495","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":"Relationship between Carnitine Deficiency and Tyrosine Kinase Inhibitor Use in Patients with Chronic Myeloid Leukemia.","authors":"Noriyoshi Iriyama,&nbsp;Katsuhiro Miura,&nbsp;Yoshihito Uchino,&nbsp;Hiromichi Takahashi,&nbsp;Masaru Nakagawa,&nbsp;Kazuhide Iizuka,&nbsp;Takashi Hamada,&nbsp;Takashi Koike,&nbsp;Kazuya Kurihara,&nbsp;Tomohiro Nakayama,&nbsp;Masami Takei,&nbsp;Yoshihiro Hatta,&nbsp;Hideki Nakamura","doi":"10.1159/000521113","DOIUrl":"https://doi.org/10.1159/000521113","url":null,"abstract":"<p><strong>Background: </strong>Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy.</p><p><strong>Objective: </strong>In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy.</p><p><strong>Method: </strong>This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy.</p><p><strong>Results: </strong>Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine.</p><p><strong>Conclusion: </strong>Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"67 2","pages":"96-101"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999387","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":"Azacitidine to Consolidate and Deepen the Therapeutic Response Achieved by Intensive Induction Treatment in a Young Patient Affected by NPM1mut-AML Who Has Become Ineligible for High-Dose Consolidation.","authors":"Natalia Cenfra,&nbsp;Gianfranco Lapietra,&nbsp;Salvatore Perrone,&nbsp;Maria Teresa Voso,&nbsp;Mariadomenica Divona,&nbsp;Sergio Mecarocci,&nbsp;Elettra Ortu La Barbera,&nbsp;Giuseppe Cimino","doi":"10.1159/000520205","DOIUrl":"https://doi.org/10.1159/000520205","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the most common leukemia in adults. In spite of the most recent discoveries about the molecular landscape of this disease, the treatment of elderly and unfit young patients continues to be a great challenge. The hypomethylating agents (HMA) still represent an effective therapeutic option for these categories, especially for the low-risk subgroups. We report the case of a young patient with NPM1mut-AML who underwent a first cycle of intensive induction treatment, achieving a complete remission, but suffered from a serious life-threatening neurologic toxicity. Due to the ineligibility to further lines of intensive chemotherapy, we decided to consolidate the response with azacitidine, administered according to the regular schedule. The minimal residual disease (MRD), monitored through the NPM1 mutation at diagnosis, progressively decreased and became undetectable after 36 cycles of hypomethylating therapy. After 1 year from discontinuation of azacitidine, MRD remains undetectable. Therefore, HMA might still represent a feasible and effective option for patients with low-risk AML, especially when the standard chemotherapy is not indicated, or as maintenance therapy in nontransplantable patients.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"67 1","pages":"24-28"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39691336","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":"miR-466 Contributes to the Enhanced Antitumor Effect of Bortezomib on Non-Small-Cell Lung Cancer by Inhibiting CCND1.","authors":"Wei-Hua Wang,&nbsp;Jia-Ming Zhan,&nbsp;Yan-Lei Tang,&nbsp;Ning Zhou,&nbsp;Wei-Yan Liu,&nbsp;Dao-Wen Jiang","doi":"10.1159/000518936","DOIUrl":"https://doi.org/10.1159/000518936","url":null,"abstract":"<p><strong>Introduction: </strong>Changes in microRNAs (miRs) contribute to the alternative chemo-resistance of cancers. Bortezomib (BTZ) is a well-characterized anticancer agent that inhibits proteasome, and its effect is associated with the function of miRs. Based on the data of microarray assay and comprehensive bioinformatics analyses, in the current study, we explored the role of miR-466 and its downstream effector CCND1 in the BTZ-resistance of non-small-cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>miR expression profiles in NSCLC tissues and paratumor tissues were determined with microarray assay. The potential miR involved in the chemo-resistance of NSCLC cells was explored via a series of bioinformatics analyses, and miR-466 was selected. Afterward, levels of miR-466 and CCND1 were investigated in NSCLC samples and analyzed by clinicopathologic parameters, including age, sex, stage of NSCLC, tumor size, tumor differentiation status, and lymphocytic infiltration status. The expression of CCND1 and miR-466 was then modulated in vitro to explore the influence on cell phenotypes, which was then verified with mouse models.</p><p><strong>Results: </strong>Based on microarray detection, 287 miRs were dysexpressed between NSCLC tissues and paratumor tissues, including 90 upregulated members and 197 downregulated members. After bioinformatics analyses and reverse transcription quantitative PCR validation, miR-466 and CCND1 were selected. Following clinical investigations, miR-466 was downregulated, while CCND1 was upregulated in NSCLC samples, contributing to the advanced cancer progression. The overexpression of CCND1 increased cell viability, suppressed cell apoptosis, decreased p21 and induced N-cadherin, CCND2, and CDK4 under BTZ treatment. The induced expression of miR-466 re-sensitized NSCLC cells to BTZ treatment. In the animal model, the overexpression of CCND1 impaired the inhibitory effect of BTZ on the growth and metastasis of solid tumor, which was restored by miR-466 induction.</p><p><strong>Conclusion: </strong>The findings showed that the interaction between BTZ, miR-466, and CCND1 determined the antitumor effect of BTZ on NSCLC.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"110-122"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39691833","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":"Molecular Characterization, Virulence Determinants, and Antimicrobial Resistance Profile of Methicillin-Resistant Staphylococcus aureus in the North of Iran; a High Prevalence of ST239-SCCmec III/t037 Clone.","authors":"Hao Ying,&nbsp;Trias Mahmudiono,&nbsp;Tawfeeq Alghazali,&nbsp;Walid Kamal Abdelbasset,&nbsp;Parand Khadivar,&nbsp;Somayeh Rahimi,&nbsp;Abolfazl Amini","doi":"10.1159/000520482","DOIUrl":"https://doi.org/10.1159/000520482","url":null,"abstract":"<p><strong>Objectives: </strong>Emergence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) have become a major universal health concern, limiting therapeutic options.</p><p><strong>Methods: </strong>A total number of 37 MRSA isolates, including 19 clinical isolates from hospitalized patients and 18 colonizing isolates from health care workers were identified from 3 hospitals, in Gorgan, North of Iran. Antimicrobial susceptibility test was performed using the disk diffusion method and E-test. The presence of virulence and antibiotic resistance determinants were evaluated by PCR. The genotypical characterization was further analyzed using multi-locus sequence, spa, staphylococcal cassette chromosome, mec (SCCmec), and agr typing.</p><p><strong>Results: </strong>The frequency of MRSA among S. aureus isolates was 38.14% (37/97). The most frequent S. aureus resistant isolates were found to be obstinate against penicillin (98%) and gentamicin (82.5%). Additionally, the lowest resistance rates were found against daptomycin (0%), vancomycin (2.7%), and quinupristin-dalfopristin (5.4%). All MRSA isolates were susceptible to daptomycin with minimum inhibitory concentration (MIC)50/MIC90 of 0.25/0.5 μg/mL. One isolate belonging to sequence type 239 (ST239)-SCCmecIII/t037 clone (MIC ≥16 μg/mL) was resistant to vancomycin. All but 1 isolate that shares ST22-SCCmec IV/t790 strain were positive for both tsst and pvl genes. The most predominant MRSA isolates (27%) were associated with ST239-SCCmec III/t037, and ST239-SCCmec III/t924 (16.2%) clones, subsequently. In our study, circulating MRSA strains were genetically diverse with a high prevalence of ST239-SCCmec III/t037 clone.</p><p><strong>Conclusion: </strong>These findings emphasize the need for future and continuous surveillance studies on MRSA to prevent the dissemination of existing multidrug resistance MRSA clones in an effective manner.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"67 1","pages":"37-46"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39697359","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":"Examining the Combination of Cefixime and Amoxicillin/Clavulanate against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates.","authors":"Haedi Thelen,&nbsp;Thomas J Dilworth,&nbsp;Renée-Claude Mercier","doi":"10.1159/000524707","DOIUrl":"https://doi.org/10.1159/000524707","url":null,"abstract":"<p><strong>Introduction: </strong>Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs.</p><p><strong>Methods: </strong>Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 μg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h.</p><p><strong>Results: </strong>AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis.</p><p><strong>Discussion/conclusion: </strong>This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"67 4","pages":"261-268"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562611","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":"Synthesis and Antimicrobial Evaluation of Amino Acid Naphthoquinone Derivatives as Potential Antibacterial Agents.","authors":"Lluvia Itzel López-López,&nbsp;Ernesto Rivera-Ávalos,&nbsp;Cecilia Villarreal-Reyes,&nbsp;Fidel Martínez-Gutiérrez,&nbsp;Denisse de Loera","doi":"10.1159/000521098","DOIUrl":"https://doi.org/10.1159/000521098","url":null,"abstract":"<p><strong>Background: </strong>The synthesis and biological evaluation of 1,4-naphthoquinone derivatives are of great interest since these compounds exhibit strong antibacterial, antifungal, antimalarial, and anticancer activities. The electronic properties of naphthoquinones are usually modulated by attaching functional groups containing nitrogen, oxygen, and sulfur atoms, which tune their biological potency and selectivity.</p><p><strong>Methods: </strong>A series of 13 amino acid 1,4-naphthoquinone derivatives was synthesized under assisted microwave and ultrasound conditions. The antibacterial activity of compounds was tested against American Type Culture Collection (ATCC): Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis, as well as 2 multidrug resistant pathogens: E. coli and S. aureus from clinical isolated. Minimal inhibitory concentration (MIC) was determined using the broth microdilution method.</p><p><strong>Results: </strong>MIC of derivatives 4-11, 14, and 16 showed antimicrobial activity against Gram-positive and Gram-negative bacteria. Antimicrobial activities of the compounds 4-8 and 14 were ≤MIC 24.7 μg mL-1 against all the reference strains; even more, compound 6 showed the most potent activity with an MIC of 3.9 μg mL-1 on S. aureus. On the clinical isolated, the compounds 7, 8, and 14 showed an MIC of 49.7 and 24.7 μg mL-1 against S. aureus and E. coli, respectively. About ADME properties and Osiris analysis, the compounds 4-16 presented high gastrointestinal absorption and good characteristics for oral bioavailability, and compound 14 was the less toxic.</p><p><strong>Conclusion: </strong>Amino acid 1,4-naphthoquinone derivatives showed good in vitro antibacterial activity against clinical strains, and modifications on C-3 with a chloride atom enhanced the efficiency against the same pathogens.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"102-109"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785401","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":"Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing.","authors":"Norihiro Sakurai,&nbsp;Hiroshi Kawaguchi,&nbsp;Gaku Kuwabara,&nbsp;Waki Imoto,&nbsp;Wataru Shibata,&nbsp;Koichi Yamada,&nbsp;Yasutaka Nakamura,&nbsp;Hiroshi Kakeya","doi":"10.1159/000522455","DOIUrl":"https://doi.org/10.1159/000522455","url":null,"abstract":"<p><strong>Introduction: </strong>Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC.</p><p><strong>Methods: </strong>We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5-24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC.</p><p><strong>Results: </strong>The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05).</p><p><strong>Conclusion: </strong>Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient's renal function but also based on BMI.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"193-200"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39899768","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":"Lung Adenocarcinoma Harboring Triple Rare EGFR Exon 18 Mutations Rapidly Developed Resistance to Multiple Therapies.","authors":"Yuyao Liu,&nbsp;Yuanqiang Wu,&nbsp;Fang Wu,&nbsp;Chunhong Hu","doi":"10.1159/000525623","DOIUrl":"https://doi.org/10.1159/000525623","url":null,"abstract":"<p><p>There is no standard therapy for nonsmall-cell lung cancer harboring rare coexistent EGFR mutations. Here, we report a female patient who was diagnosed as lung adenocarcinoma with three mutations of G724S, E709K, and V689I in exon 18. The patient responded to, but also showed rapid development of resistance to multiple therapies, including a second-generation EGFR-TKI of afatinib, a platinum-based doublet chemotherapy, and a multiple target TKI of anlotinib. As such, she ended up with a short overall survival time. Further research is required to understand the resistance mechanism(s) of these complex gene mutations.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"248-252"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40406983","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":"Curcumin Suppresses the Progression of Colorectal Cancer by Improving Immunogenic Cell Death Caused by Irinotecan.","authors":"Cunliang Zhu,&nbsp;Zhaobi Fang,&nbsp;Lei Peng,&nbsp;Fan Gao,&nbsp;Wei Peng,&nbsp;Fengqian Song","doi":"10.1159/000518121","DOIUrl":"https://doi.org/10.1159/000518121","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan (IRI) is a common chemotherapeutic drug for colorectal cancer; however, the mechanism underlying its immunomodulatory effect remains unclear. Curcumin (CUR), an adjuvant drug with anti-inflammatory and antitumor effects, has been studied extensively, although its synergistic antitumor effect remains unclear.</p><p><strong>Methods: </strong>The effects of CUR and IRI on oxidative stress and their antitumor effects were detected by flow cytometry. Endoplasmic reticulum stress-related proteins including CHOP and BiP, and immunogenic cell death (ICD) proteins including calreticulin (CALR) and high mobility group box 1 (HMGB1), were detected by Western blotting. IFN-γ and TNF-α levels in the serum of mice were detected by ELISA.</p><p><strong>Results: </strong>IRI in combination with CUR had synergistic antitumor effects in CT-26 colon carcinoma cells. Combination treatment with IRI and CUR was more effective than IRI or CUR alone. IRI and CUR combination treatment significantly upregulated ICD-related proteins including CALR and HMGB1 and had a greater antitumor effect than IRI or CUR single treatment in vivo. CUR may synergistically improve the antitumor effect of IRI by promoting the ICD effect.</p><p><strong>Conclusion: </strong>Combination therapy with IRI and CUR may be an option for first-line chemotherapy in some patients with advanced colorectal cancer.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"211-222"},"PeriodicalIF":3.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40468020","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}