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Leukemia, a hematological malignancy originating from the bone marrow, is the principal cancer of childhood. In recent decades, improved remission rates and survival of patients with leukemia have been achieved due to significant breakthroughs in the treatment. However, chemoresistance and relapse are common, creating an urgent need for the search for novel pharmaceutical interventions. 1,2,3-Triazole is one of the most fascinating pharmacophores in the discovery of new drugs, and several 1,2,3-triazole derivatives have already been used in clinics or are under clinical evaluation for the treatment of cancers. In particular, 1,2,3-triazole hybrids could suppress tumor proliferation, invasion, and metastasis by inhibiting enzymes, proteins, and receptors in cancer cells, revealing their potential as putative antileukemic agents. This review covers the recent advances regarding the 1,2,3-triazole hybrids with potential antileukemic activity, focusing on the chemical structures, structure-activity relationship, and mechanisms of action, covering articles published from January 2017 to January 2022.
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Antineoplásicos , Leucemia , Neoplasias , Antineoplásicos/química , Humanos , Leucemia/tratamento farmacológico , Estrutura Molecular , Neoplasias/tratamento farmacológico , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologiaRESUMO
Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies, and once metastasis occurs, it often has a poor prognosis and lacks effective treatment. Therefore, there is an urgent need to screen some new biomarkers and explore their molecular mechanisms to improve the early clinical diagnosis and targeted therapy of ccRCC. SPOCK1 (SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1) is a conserved multi-domain proteoglycan that plays an important role in the development of multiple cancer types; however, its prognostic value in ccRCC has not been investigated. The study of the prognostic value of SPOCK1 in ccRCC is a good complement to the study of ccRCC biomarkers. Methods: Databases of this study included Oncomine, Kaplan-Meier Plotter, GEPIA, GeneMANIA, cBioPortal, and TIMER. Student's t-test was used to analyze the differences in SPOCK1 expression in ccRCC tissues compared with tumor-adjacent normal tissues. Kaplan-Meier curves for survival analysis were used to assess the correlation between the expression of SPOCK1 and the prognostic outcomes. Correlation module drew the expression scatterplots between SPOCK1 and immune cell infiltration in ccRCC, together with the Spearman's rho value and estimated statistical significance. Results: The SPOCK1 mRNA expression was significantly higher in ccRCC tissues (mean expression ± SD: 920.2±195.2) than in normal tissues (mean expression ± SD: 358.4±29.1, P=0.008), and high SPOCK1 expression significantly and positively correlated with the pathological stage of ccRCC patients (F value =10.2, P<0.001). Higher expression of SPOCK1 was also associated with significantly shorter overall survival (OS) and disease-free survival (DFS) in ccRCC patients (GEPIA: P=0.046, P<0.001, respectively; Kaplan-Meier Plotter: P=0.002, P=0.0022, respectively). The function of SPOCK1 is mainly related to tumor development and extracellular matrix remodeling, and it may participate in the epithelial-mesenchymal transition process. SPOCK1 expression significantly and positively correlated with infiltration of several immune cells in ccRCC, including cancer-associated fibroblasts (CAFs) (Rho =0.333, P=2.16×10-13), tumor-associated macrophages (TAMs) (Rho =0.18, P=1.02×10-4), and tumor-associated neutrophils (TANs) (Rho =0.165, P=3.83×10-4). Conversely, there was a significant and negative correlation between SPOCK1 expression and infiltration of CD4+ T cells (Rho =-0.113, P=0.015). Conclusions: SPOCK1 may be a potential prognostic biomarker in ccRCC.
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Objective: Meta analysis was used to explore the efficacy and safety of Sintilimab in the treatment of cancer. Methods: The databases of CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, the Cochrane Library and EMBASE were searched by computer to collect the randomized controlled trials published as of March 2022. The retrieval work was completed by two researchers alone. They screened the literature and extracted the data according to the nanodischarge standard, using Revman 5.4 software. The included studies were statistically analyzed. Results: Six RCTs were included in this study, including 1,048 cases of Sintilimab and 711 cases of other anticancer drugs. Compared with the control group, the overall survival (HR = 1.64, 95% CI: 1.35-1.99, p < 0.00001) and progression free survival (HR = 1.89, 95% CI: 1.59-2.25, p < 0.00001) of cancer treated with Sintilimab were longer and more effective. Moreover, the risk ratio of any grade of adverse reactions (HR = 0.87, 95% CI: 0.74-1.03, p = 0.11) and above grade III adverse reactions (HR = 0.84, 95% CI: 0.67-1.06, p = 0.14) in the treatment of cancer with Sintilimab was lower and the safety was better. Conclusion: Compared with non-Sintilimab group, Sintilimab treatment can improve the clinical efficacy of tumor patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for cancer patients.
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Objective: Meta analysis was used to compare the efficacy and safety of immune checkpoint inhibitor and docetaxel in the treatment of non-small cell lung cancer. Methods: CNKI, CBM, PubMed, EMBASE, Cochrane Library, web of science and other databases were searched by computer, and the randomized controlled trials of immune checkpoint inhibitors and docetaxel in the treatment of NSCLC published as of February 2022 were collected. Two researchers searched independently, screened the literature and extracted the data according to the nanodischarge criteria, and used Revman5.4. The included studies were statistically analyzed, and publication bias was analyzed with Egger test in Stata12. Results: A total of 8 RCTs were included, including 2444 cases treated with immune checkpoint inhibitors and 2097 cases treated with docetaxel. Compared with docetaxel, the overall survival (HR = 1.40, 95%CI: 1.30-1.50, P < 0.00001) and progression free survival (HR = 1.22, 95%CI: 1.13-1.32, P < 0.00001) of NSCLC treated with ICIs were longer. The risk ratio of any grade of adverse reactions (HR = 0.41, 95%CI: 0.32-0.52, P < 0.00001) and above grade III adverse reactions (HR = 0.27, 95%CI: 0.18-0.41, P < 0.00001) in the treatment of NSCLC with ICIs was lower. There was no publication bias in Egger test. Conclusion: Compared with docetaxel, immune checkpoint inhibitor treatment can improve the clinical efficacy of NSCLC patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for NSCLC patients.
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OBJECTIVE: In this study, we sought to investigate the distribution characteristics, early diagnosis, and related risk factors of multidrug-resistant organism (MDRO) in patients with malignant tumors. METHODS: A total of 278 patients with malignant tumors and infections were selected in the Department of Oncology for retrospective study, including 128 MDRO patients and 150 non-MDRO patients. The markers of bacterial culture were detected, and the serum procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) levels were measured in patients' blood samples. The diagnostic value of PCT, CRP, and SAA for MDRO was evaluated, the distribution of MDRO in different years and different infection sites was analyzed, and the related risk factors of MDRO infection were studied. RESULTS: The PCT, CRP, and SAA in the MDRO group were significantly higher than those of the non-MDRO group (all P<0.001). The area under the curve of receiver operating characteristics for the diagnosis of MDRO by PCT, CRP, and SAA. The combination of the three was 0.792, 0.811, 0.755, and 0.842, respectively. The distribution of MDRO strains in different years was statistically different (P<0.05), as well as the distribution of MDRO in different infection sites (P<0.05). Multivariate regression analysis demonstrated that invasive operation, excessive bed rest, hypoproteinemia, PCT, and SAA were independent risk factors for MDRO infection in patients with malignant tumors (all P<0.05). CONCLUSION: The combination of CRP, PCT, and SAA displays a value for early diagnosis of MDRO infection. MDRO infections in malignant tumors mainly include carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Escherichia coli. There are differences in terms of MDRO strains in different years and different infection sites, and there are many risk factors regarding MDRO infection in patients with malignant tumors. Intervention should be taken in order to reduce the rate of MDRO infection.
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Four new flavonoids were isolated from Campylotropis hirtella and these are a chromone and a 2H-chromene, an isoflavone and an isoflavanonol. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Compound 4 showed very strong T lymphocyte suppression activity (IC50: 0.13 µM) and potent B lymphocyte suppression activity (IC50: 0.26 µM). Due to its potent immunosuppressive activity and lower cytotoxicity, further structure-activity studies will be pursued on this compound.
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Fabaceae/química , Imunossupressores/química , Imunossupressores/farmacocinética , Isoflavonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Cromonas/química , Cromonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Concentração Inibidora 50 , Isoflavonas/química , Isoflavonas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
In an effort to identify natural compounds with immunosuppressive activity, nine new flavonoids, including one isoflav-3-ene derivative (1), one coumaronochromone (2), two isoflavanones (3, 4), one isoflavone derivative (6), one isoflavone (7), three flavonols (8, 9, 10), as well as one known compound, hydroisoflavone C (5), were isolated from the roots of Campylotropis hirtella. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Among the isolates, compound 2 showed good inhibitory activity against mitogen-induced splenocyte proliferation with an IC50 of 0.28 µM and relatively low cytotoxicity.