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Patients with gastric cancer often have different degrees of dyslipidemia, and the level of lipid changes is closely related to the occurrence, development and prognosis of gastric cancer. The mechanism of lipid metabolism in gastric cancer has also attracted much attention, and it may be related to the reverse cholesterol transport function, antioxidant and anti-inflammatory properties of high-density lipoprotein cholesterol. In addition, statins may reduce the risk of gastric cancer and associated mortality. Further research on the correlation between blood lipid levels and gastric cancer is aimed to provide new ideas for the future prevention and precision diagnosis and treatment of gastric cancer.
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Immunotherapy for gastric cancer has recently received attention. As a result, the guidelines for diagnosis and treatment of advanced gastric cancer have been revised. Many clinical studies have begun to pay attention to perioperative immunotherapy for gastric cancer. This article discusses the perioperative treatment of gastric cancer in the new era of immunity to contribute to the hot issues in this field.
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Antibody-drug conjugates (ADCs) are novel drugs consisting of monoclonal antibodies targeting tumor-specific or tumor-associated antigens coupled with different numbers of payloads via linkers. ADCs have shown promising clinical benefits in the treatment of a variety of malignancies. Small-cell lung cancer (SCLC) is a hypo-differentiated neuroendocrine tumor with an extremely high degree of malignancy. Although SCLC is sensitive to radiotherapy and chemotherapy, it has a poor prognosis due to characteristics such as early susceptibility to metastasis and recurrence. Progress in the treatment of SCLC is very limited, and more durable and effective therapies should be developed to improve prognosis. However, the progress of SCLC-related therapeutic agents has been limited by the lack of specific molecular targets. This article reviews the basic principles and mechanisms of ADCs, highlights the research progress of relevant drugs against some targets in SCLC, and summarizes new targets that may be developed as targeted drugs.
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Objective:To explore the alteration of JAK2/STAT3 pathway after carbon ion ( 12C 6+) irradiation and the difference in the infiltration of CD8 + T cells in lung cancer regulated by downstream protein FOXP3. Methods:Significantly altered JAK2/STAT3 pathway and related differentially-expressed genes and proteins such as FOXP3 in lung cancer after carbon ion irradiation were screened based on RNA sequencing analysis in the Lewis tumor model of C57BL/6 mice. The correlation between FOXP3 and major immune cell infiltration in the immune microenvironment of lung cancer was analyzed using the ssGSEA immune infiltration algorithm in the R software "GSVA" and CD8 + T cell infiltration in the immune microenvironment of lung cancer was evaluated based on the carbon ion combined with STAT3 inhibition pathway (niclosamide). Results:The JAK2/STAT3 pathway was inhibited and the expression of related genes and proteins was downregulated in lung cancer after carbon ion irradiation. Immune scoring based on the ssGSEA algorithm showed that FOXP3 expression was significantly negatively correlated with CD8 + T cell infiltration in the immune microenvironment of lung cancer. The role of targeting the JAK2/STAT3 pathway in increasing CD8 + T cell infiltration in lung cancer was further clarified by carbon ion irradiation combined with STAT3 inhibition (niclosamide). Conclusion:Carbon ion irradiation ( 12C 6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.
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Although targeted, immune and other therapeutic strategies have become the first-line standard therapy for patients with advanced lung cancer, acquired drug resistance is still inevitable in most cases. The advent of antibody-drug conjugates (ADC) provides a new choice. ADC is a new anticancer drug formed by the coupling of targeted anti-tumor monoclonal antibodies and cytotoxic drugs. Compared with chemotherapeutic drugs, ADC has the advantages of high tolerance, accurate target recognition and little effect on non-cancer cells, and has shown good clinical benefits in the treatment of a variety of malignant tumors. This article reviews the application of ADC in advanced non-small cell lung cancer.
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Objective:To explore the effects of myosteatosis and blood glucose (BG) on postoperative complications in non-diabetic gastric cancer patients receiving supplemental parenteral nutrition (SPN) after gastrectomy.Methods:Patients who underwent radical gastrectomy between March 2017 and June 2021 in the Department of Surgical Oncology, the First Hospital of Lanzhou University were included in this study. Various preoperative inflammatory and nutritional indicators, including skeletal muscle metrics at the third lumbar level on CT, were collected retrospectively. Postoperative BG within 3 days and complications within 30 days were monitored. Patients were divided into two groups according to the presence or absence of myosteatosis (assessed via skeletal muscle density [SMD]) and the differences in postoperative BG and complication incidence were compared. Mediation model was used to analyze the mediating effect of BG in the association between SMD and postoperative complications.Results:A total of 357 patients were included in the study. Compared with the 299(83.8%) patients without myosteatosis , the incidence of hyperglycemia, mean BG, maximal BG, and BG fluctuation while on SPN in the 58(16.2%) patients with myosteatosis were higher, and the comprehensive complication index (CCI) and the incidence of complication were higher ( P<0.05). More importantly, BG showed the mediation effect of -0.0892 in the effect of SMD on CCI ( P<0.05), with the effect size of 19.3％. Conclusion:Myosteatosis and postoperative hyperglycemia are associated with higher incidence of complications, and BG plays an intermediary role in the association between myosteatosis and CCI.
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Heavy ion radiation has significant radiological and biological advantages over conventional radiation. While directly killing tumor cells, heavy ion beam can reduce immune escape and promote the initiation and activation of effector T cells by inducing immunogenic death of tumor cells, regulating tumor phenotype, enhancing antigen formulation, and changing tumor microenvironment to regulate the immune response. This article will review the immunomodulatory effect of heavy ion beam and the molecular mechanisms associated with immune checkpoint inhibitor therapy.
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Objective: To detect the expression of P53, human epidermal growth factor receptor-2 (HER-2), and tumor endothelial marker 1 (TEM1) in gastric cancer tissues, analyze their correlation with clinical efficacy, and explore their potential roles as biomarkers for neoadjuvant chemotherapy. Methods: Sixty-three patients with gastric cancer who underwent fluorouracil-based neoadjuvant che-motherapy in The First Hospital of Lanzhou University from May 2015 to May 2017 were enrolled. Using immunohistochemistry, the expression of P53, Her2, and TEM1 was detected in 63 gastric cancer specimens before neoadjuvant chemotherapy. The efficacy of neoadjuvant chemotherapy was assessed by imaging. The relationship between the expression of P53, HER-2, and TEM1 and the effi-cacy of neoadjuvant chemotherapy was analyzed. Results: The total effective rate of neoadjuvant chemotherapy in 63 patients with advanced gastric cancer was 69.8%, with 2, 7, and 35 patients achieving complete remission, partial remission, and stable disease, re-spectively. Disease progression was noted in 19 patients. Univariate analysis revealed that patients positive for TEM1 and having high T stage had a poor response to neoadjuvant chemotherapy (P<0.05); furthermore, location, differentiation, and size of tumor; P53 posi-tivity (P=0.488); and Her-2 positivity (P=0.106) were not associated with the efficacy of neoadjuvant chemotherapy for gastric cancer. Multivariate analysis revealed that TEM1 positivity and a higher T stage could be factors that predicted the response to neoadjuvant chemotherapy in patients with advanced gastric cancer. Conclusions: TEM1, as a marker of tumor stroma, may be an important molec-ular biological indicator that predicts the poor response to neoadjuvant chemotherapy in patients with gastric cancer.
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Taurine-upregulated gene 1 (TUG1) is a recently identified oncogenic long non-coding RNA (lncRNA),that is overexpressed in various digestive system tumor tissues and cell lines,including esophageal cancer,gastric cancer,liver cancer,cholangiocarcinoma and biliary tract cancer,pancreatic cancer and colorectal cancer.Studies have shown that TUG1 participates in tumor cells proliferation,apoptosis,migration and invasion,and high expression of TUG1 is associated with clinicopathological features and prognosis of cancer patients,suggesting that lncRNA TUG1 is likely represents a feasible biomarker or therapeutic target in human digestive system cancers.
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Anti-neovascularization is an important research direction in the current treatment of gastric cancer.The inhibitors of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) are main research focus.At present,the inhibitors of the pathways of VEGF and VEGFR in the treatment of advanced gastric cancer include bevacizumab,ramucirumab,apatinib,regorafenib,sorafenib,et al.These drugs provide more possibilities for the treatment of advanced gastric cancer.
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Studies have found that obesity is not only closely related with the occurrence and development of breast cancer,but also can significantly increase the risk of breast cancer recurrence and death,especially the occurrence of postmenopausal estrogen receptor positive breast cancer.Therefore,it is of great importance to understand the influence of obesity on the prognosis of breast cancer.The intervene of diet and lifestyle,metformin and other drags,and other obesity targeted therapies have provided direction for future research on these influence.
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Gastric cancer is a high-risk tumor in China,with high malignant degree,high mortality and poor prognosis.Hematological indexes are preoperative routine examination with low prices.Hematological indexes (such as tumor markers,inflammation index,etc) can be used to overall evaluate tumor size,depth of invasion,lymph node metastasis and recurrence of gastric cancer patients,which are helpful for us to better understand the surgical risks,and take preventive measures and improve the survival rate.
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Objective To explore the association between Xeroderma pigmentosum complementation C group (XPC) Lys939Gln (A/C) gene polymorphism and the susceptibility of gastric cancer.Methods By searching PubMed,Cochrane Library,Elsevier,Springer-Verlag,China National Knowledge Infrastructure,Chinese Biomedical Literature Data,VIP Database and Wanfang Database,all eligible case-control studies published up to September 2015 were selected and the quality of each article was valuated by two reviewers independently according to the inclusion and exclusion criteria.Meta-analysis was performed by using STATA 12.0 software.Odds ratio (OR) and 95％ confidence interval (CI) were calculated.The text was estimated for the subgroup analysis,sensitivity analysis and publication bias test.Results A total of 7 case-control studies were included,including 2 336 cases with gastric cancer and 3 502 controls.The Meta-analysis showed that compared with the allele A,the allele C increased the risk of gastric cancer (OR =1.09,95％ CI:1.01-1.18,Z =2.12,P =0.034);compared to the genotype AA,the homozygous model (CC) and dominant model (CC + AC) also increased the risk of gastric cancer (CC vs.AA:OR =1.19,95％ CI:1.00-1.42,Z =2.00,P=0.046;CC+ACvs.AA:OR=1.12,95％CI:1.00-1.25,Z=2.03,P=0.042).The Meta-analysis showed the statistical significance between XPC Lys939Gln (A/C) gene polymorphism and the gastric cancer risk in subgroup of Asian people (C vs.A:OR =1.10,95％ CI:1.01-1.20,Z =2.28,P =0.023;CC vs.AA:OR=l.21,95％CI:1.01-1.46,Z=2.02,P=0.043;CC +AC vs.AA:OR =1.13,95％ CI:1.01-1.27,Z =2.11,P =0.035) and the source of community in the control group (C vs.A:OR =1.11,95％ CI:1.01-1.21,Z=2.25,P =0.024;CC vs.AA:OR =1.23,95％ CI:1.02-1.50,Z =2.12,P =0.034).Conclusion XPC Lys939G1n (A/C) gene polymorphism may be associated with the susceptibility of gastric cancer,and genotype CC,CC + AC and allele C can increase the risk of gastric cancer.
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Objective To quantitatively examine the relationship between xeroderma pigmentosum complementation C group (XPC)rs2228000 (C /T)polymorphism and the susceptibility of breast cancer. Methods The relevant case-control studies published up to December 2015 which investigated XPC rs2228000 (C /T)polymorphism and breast cancer risk were identified by searching PubMed,Cochrane Library,Chinese Biomedical Literature Data,Wanfang Database,China National Knowledge Infrastructure and VIP Database. Meta-analysis was conducted using STATA 12.0 software and odds ratio (OR)with its 95%CI were estimated. Results A total of 8 researches involving 9 case-control studies (3 850 breast cancer cases and 5 047 healthy controls) were included.The Meta-analysis showed that there was statistical association between XPC rs2228000(C /T)variance and breast cancer risk in the homozygous model (TT vs.CC:OR =1.28,95%CI:1.08-1.52,Z =2.80,P =0.005)and recessive model (TT vs.TC +CC:OR =1.23,95%CI:1.05-1.43, Z =2.64,P =0.008),but not in the allele model,heterozygote model and dominant model.In the subgroup of ethnicity and genotyping methods,the different significant correlation was existed between them under Asian and PCR-RFLP in genetic models (T vs.C:OR =1.21,95%CI:1.05-1.40,Z =2.63,P =0.009;TT vs. CC:OR =1.55,95%CI:1.13-2.13,Z =2.70,P =0.007;TT +TC vs.CC:OR =1.26,95%CI:1.02-1.55,Z =2.19,P =0.028;TT vs.TC +CC:OR =1.39,95%CI:1.04-1.87,Z =2.23,P =0.026).We also found significant association between them in subgroup of population-based controls in the homozygous model (TT vs.CC:OR =1.27,95%CI:1.02-1.57,Z =2.16,P =0.031).Conclusion XPC rs2228000 (C /T)polymorphism may be associated with the susceptibility of breast cancer,especially in Asian,and gene-type TT may increase the risk of breast cancer.
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Objective To assess the association between glutathione S-transferase T1 (GSTT1 )gene and the susceptibility of colorectal cancer among Chinese population.Methods Clinical controlled trials of the association between GSTT1 and the susceptibility of colorectal cancer among Chinese population were searched in PubMed,EMBase,Cochrane Library,China Biology Medicine disc,VIP database,China National Knowledge Infrastructure and Wanfang database.According to the inclusion and exclusion criteria,data extraction and quali-ty assessment were done by two researchers independently.Outcomes were pooled with RevMan 5.1 .Results 326 studies were found and 10 clinical controlled trails including 2 983 cases of colorectal cancer and 4 386 cases of healthy objects were included in this analysis.The results of Meta-analysis showed that the lack of GSTT1 gene is associated with colorectal cancer susceptibility (RR =1 .11 ,95%CI:1 .06-1 .17,Z =4.26,P <0.000 1 ). Conclusion The loss of GSTT1 increase the risk of colorectal cancer among Chinese population.
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Objective To quantitatively evaluate the association between Ile105Val polymorphism of glutathione S-transferase pi (GSTP1) and sensitivity to platinum-based chemotherapy in advanced gastric cancer.Methods The relevant published literatures about Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in gastric cancer were retrieved from China National Knowledge Internet (CNKI),VIP,Chinese Biomedical Literature Data (CBM),Wan-Fang databases,PubMed,EMBASE and Cochrane Library.Clinical response (complete response and partial response) was employed to estimate chemosensitivity.Meta-analysis was conducted by the RevMan 5.2 software,odds ratio (OR) with 95％ confidence interval (CI) were calculated.Publication bias was identified using Stata 12.0 software.Results A total of 724 cases from 6 case-control trials were included.The results of Meta-analysis showed the different statistical significance was found between GSTP1 Ilel05Val polymorphism and clinical response in the follow genotypes [GG+GA vs AA:OR =2.38,95％CI (1.29 ～4.38); GG vs GA + AA:OR =3.66,95％CI (1.18 ～11.39) ; GG vs AA:OR =4.42,95％ CI (1.28 ～ 15.26)] and Asian population subgroups [GG + GAvs AA:OR =2.93,95％ CI (1.33 ～ 6.48)].Conclusion Polymorphism of GSTP1 Ile105Val(A/G) may be associated with platinum-based chemosensitivity in advanced gastric cancer.
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Regulatory T cells (Treg),a group of negative regulatory cells,have four subsets:CD4+Treg,CD8 + Treg,NKT Treg and DN Treg cells.They play an essential role in the inhibitive immune-regulation and might be the key factors of neoplasms immune escape.These mechanisms include inhibiting the effector cell function by inhibitory cytokines,killing effector cells by granzyme and perforin,competition and inhibiting IL-2,and affecting Treg differentiation and proliferation by regulating the function of CTLA-4,etc.Tumor immunotherapies targeting Treg and related immunosuppressive factors,such as remove Treg or controling the numbers and functions,enhances the immune response against tumors,which might offer a new method of tumor immunotherapy.
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Glucose metabolism of cancer cells presents Warburg effect.In resent years,more and more experiments demonstrate that the therapeutics based on aerobic glycolysis pathway in cancer cells restrict energy and inhibit tumor proliferation through the inhibition of a variety of moleculars,genes and signal pathways.These can provide an opportunity for targeted cancer therapies and possess enormous potential advantages and broad prospects in clinical application.
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Objective To assess the effect of aspirin for the chemoprevention of colorectal adenomas by meta analysis of the published literature.Methods Cochrane strategy in combination with manual search was used to identify previously published randomized controlled trials by searching PubMed,EMBase,Cochrane Library,China Journal Full-text Database(CNKI),Chinese Scientific Journal Full-text Database (CSJD) and Chinese Biomedical Literature Database (CBM).Results Six randomized controlled trials involving a total of 2 858 patients were studied.Of the six trials,two trials were performed in China,four trials were in the Europe and the United States.Some sufficient evidence were found to support that aspirin could prevent of colorectal adenomas compared with placebo group ( P =0.003,RR =0.66,95％ CI:0.50-0.86).No adaquate evidence supported the role of aspirin in the prevention of development of colorectal cancer ( P =0.29,RR =0.65,95％ CI:0.30-1.44).High-dose aspirin ( P =0.10,RR =0.85,95％ CI:0.71-1.30 ) and low-dose aspirin could prevent colorectal adenomas compared with placebo group( P =0.02,RR =0.57,95％ CI:0.36-0.90),and a dose-dependent associtation was found.The risk of stroke was higher in any dose of aspirin compared with placebo group ( P =0.04),and the risks of adverse events had no significant differences in all groups.Conclusion Aspirin might prevent the development of colorectal adenomas in individuals,but could not prevent the colorectal cancer.
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Cancer stem cells are a subclass of stem-cell-like tumor cells.They have an apparently higher tumorigenicity than other cell populations within the same tumor.They play a Very important role in genesis,development and maintenance of cancer.The data from research in leukemia and solid timors suggest that in each cancer tissue,only a small fraction of the cells have the ability to initiate tumor,which are called cancer stem cells.In recent years,with in-depth research on stem cells and cancer stem cells,accumulating evidence suggests that cancer stem cells are the cause of malignant tumor metastasis and recurrence and are resistant current callcer drugs.Drugs targeting cancer stem cells are urgently needed. Flow cytometry and magnetic cell sorting using the identified tumor stem cell surface markers are mainly used to separate cancer stem cells or stem cell-like cells. In this article,the concept of cancer stem cells and the commonly used approaches to isolate and identify cancer stem cells,especially for gastric cancer stem cells will be reviewed.