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The emergence of immune checkpoint inhibitors holds new promise for patients with small cell lung cancer. Studies have found that PD-L1 expression, tumor mutation burden, genomic characteristics, peripheral blood parameters and other indicators can be used as prognostic predictors in patients with small cell lung cancer receiving immunotherapy. Further exploration and evaluation of relevant predictors can provide a reference for screening patients with potential benefits of immunotherapy.
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Pancreatic cancer is one of the fatal malignant tumors, and its dense stroma, which accounts for 90% of the volume of pancreatic tumor, is the main reason for the low survival rate of pancreatic cancer. Cancer-associated fibroblasts (CAFs) are an important group of cells in the tumor stroma of pancreatic cancer, and activated CAFs induce a strong connective tissue interstitial reaction and secretes a variety of soluble molecules to remodel the extracellular matrix, thereby forming a microenvironment that helps with the proliferation, invasion, and metastasis of pancreatic cancer. At present, an increasing number of evidence has shown that CAFs play an important role in the drug resistance of pancreatic cancer, especially in chemotherapy and immunotherapy, and CAFs result in a low response rate of pancreatic cancer treatment by interfering with the metabolism of antitumor drugs, participating in the signaling pathways associated with drug resistance, and forming an immunosuppressive microenvironment. This article elaborates on the specific mechanism of CAFs participating in the drug resistance of pancreatic cancer from the two aspects of chemotherapy and immunotherapy, in order to provide new ideas for identifying new therapeutic targets for pancreatic cancer and improving the response rate of pancreatic cancer treatment.
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Immunotherapy is a new anti-tumor method. The application of immune checkpoint inhibitor greatly improves the survival benefit for patients, but the drug resistance of immunotherapy affects the efficacy. Therefore, it is very important to explore the mechanism of drug resistance and solve the problem of drug resis-tance in tumor immunotherapy. Hypoxia in tumor microenvironment is the key factor of immune drug resistance. Hypoxia can inhibit the immune cells function and lead to immune escape through various mechanisms. It can be the breakthrough for overcoming the immunotherapy drug resistance that blocking pathway of hypoxia to promote immune resistance. By reviewing the mechanism of immunotherapy drug resistance induced by hypoxia, it is helpful to explore the development prospect of hypoxia-inducible factor-1α (HIF-1α) related targeted drugs in clinical application for immunotherapy.
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Objective:To investigate the risk factors, clinical features and prognosis of abnormal liver function after receiving oxaliplatin-containing chemotherapy regimen in patients with colorectal cancer, and to provide a relevant basis for clinical diagnosis and treatment.Methods:The clinical data of 108 colorectal cancer patients who received XELOX (oxaliplatin+capecitabine) or mFOLFOX6 (oxaliplatin+leucovorin+ 5-fluorouracil) chemotherapy regimen from October 2017 to May 2019 in the First Hospital of Shanxi Medical University were analyzed retrospectively. According to the liver function indexes after chemotherapy, the patients were divided into abnormal liver function group and normal liver function group. The observation indexes included alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase. The clinical characteristics of liver dysfunction after oxaliplatin-containing chemotherapy were analyzed and the related factors that might lead to liver dysfunction were analyzed by using multivariate logistic regression analysis.Results:Among 108 patients receiving chemotherapy, there were 67 (62.0%) cases of abnormal liver function. The main grades of liver dysfunction were grade 1 and grade 2, including 49 cases of grade 1 (73.1%) and 16 cases of grade 2 (23.9%). After chemotherapy, the abnormal liver function usually began in 1-4 cycles, of which 22 cases were 1 cycle (32.8%), 17 cases were 2 cycles (25.4%), 20 cases were 3 cycles (29.8%), and 4 cases were 4 cycles (6.0%). Univariate analysis showed that the age <60 years old, chemotherapy cycle >6, the use of mFOLFOX6 regimen, unprotected hepatoprotective drugs were related to liver dysfunction ( χ2 values were 3.910,4.799, 12.861, 4.044; all P < 0.05). Multivariate logistic regression analysis showed that mFOLFOX6 regimen and unprotected hepatoprotective drugs were independent risk factors of abnormal liver function ( HR = 3.405, 95% CI 1.266-9.159, P = 0.015; HR = 2.348, 95% CI 1.012-5.477, P = 0.047). Conclusions:For patients with colorectal cancer who have a high risk of liver dysfunction after chemotherapy, it is recommended to prefer XELOX regimen among oxaliplatin-containing chemotherapy regimens and to take preventive liver protection treatment.
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Purpose@#Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC. @*Materials and Methods@#HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell,and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p,and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model. @*Results@#CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients,high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo. @*Conclusion@#CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.
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Objective To investigate the effect of transcatheter arterial chemoembolization (TACE)combined with radiofrequency ablation (RFA) in the treatment of liver cancer,and its influence on the serum markers.Methods 108 patients with primary liver cancer were selected as the subjects of this study.According to the random number table method,the patients were divided into two groups.The control group (54 cases) received TACE treatment,and the observation group (54 cases) received TACE combined with RFA treatment.The treatment effects,the changes of tumor recurrence related indicators and the levels of tumor related indicators were compared and analyzed.Results The effective rate of the observation group was 79.7 ％ (43/54),which was significantly higher than 50.0％ (27/54) of the control group (x2 =10.391,P =0.001).After treatment,the E-calcium protein (EC),vascular endothelial growth factor (VEGF),matrix metalloproteinase (MMP),tumor recurrence index alpha fetoprotein (AFP),CA199,glutamate transferase (GGT) levels in the observation group were (1 738.8 ± 114.8) μg/L,(207.9 ± 37.2) ng/L,(34.9 ± 4.6) ng/L,(72.2 ± 19.5) μg/L,(34.2 ± 5.1) U/L,(88.9 ± 9.4) U/L,respectively,which were significantly lower than those in the control group [(2 382.4 ± 159.4) μg/L,(367.3 ± 49.3) ng/L,(72.1 ± 7.4) ng/L,(135.2 ± 21.8) μg/L,(66.9 ± 8.2) U/L,(124.6 ± 12.5) U/L],the differences were statistically significant(t =24.076,18.967,31.373,15.828,24.884,16.774,all P ＜0.05).Conclusion TACE combined with RFA is effective in the treatment of liver cancer,which can effectively kill tumor cells and reduce the contents of serum tumor markers,and it is worthy of popularizing in clinic.
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Objective To observe the inhibitory effect of xiaoaiping injection and octreotide on H22 tumor-bearing mice and find the best drug concentration,then to explore its mechanism.Methods Establish a mouse H22 subcutaneous tumor model.After tumor the experiment animals were divided into normal control group,model group,Xiaoaiping low,medium and high dose group,octreotide group,and the group of XAP low,medium and high dose groups were combined with OCT.Calculate the tumor's volume and draw the tumor growth curve.Intraperitoneal injection for 14 days,Inhibitory rate was calculated; To observe its pathological changes by light microscope; The ratio.of CD3 + NK1.1-T cells,CD3-NK1.1 + NKcells,CD3 + NK1.1 + NK-Tcells in peripheral blood were measured by flow cytometry.Results Compared with the control group,H22 liver cancer in different treatment group had a certain inhibition effect on growth,The inhibitory effect of the combination group was better than single-agent group,High-dose Xiaoaiping + octreotide was best,Tumor model group compared with normal control group,The ratio of T cells,NK cells and NKT cells was significantly lower(P ＜0.05) ; T cells,NK cells and NKT cells after treatment in each group had some enhancement,High-dose Xiaoaiping + octreotide was the most obvious,the ratio of T cells,NK cells and NKT cells of the combination group was significantly more than the single-drug group and the same concentration of octreotide monotherapy Xiaoaiping group(P ＜ 0.05).Conclusion High-dose Xiaoaiping + octreotide is the best drug for the inhibitory drug concentration.The inhibition of tumor growth may pass to improve the tumorbearing mice with immune status and enhance the body's anti-tumor capacity.