BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regim...BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase III clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.展开更多
Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can p...Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.展开更多
The prevalence of malnutrition is high among oncology patients in China. Although the Patient- Generated Subjective Global Assessment (PG-SGA) is widely recognized as an important nutritional assessment tool, it has n...The prevalence of malnutrition is high among oncology patients in China. Although the Patient- Generated Subjective Global Assessment (PG-SGA) is widely recognized as an important nutritional assessment tool, it has not been validated for Chinese cancer patients. The purpose of this study was to conduct an analysis of nutrition screening and assessment data to validate the Chinese version of the PG-SGA in Chinese patients with lung cancer. This was an observational, cross-sectional study of 2,000 consecutive adult patients with lung cancer treated at several tertiary hospitals in China. Anthropometric and patient descriptive data were collected. The PG-SGA generated a score for the nutritional risk and a global rating for the nutritional status. The internal consistency, external consistency, and construct validity were evaluated, and a known-groups comparison and principal component analyses were conducted to evaluate the reliability and validity of the PG-SGA. The known-groups comparison demonstrated the ability of the PG-SGA to differentiate lung cancer patients of different nutritional and body mass index (BMI) groups. A confirmatory factor analysis supported the original four-factor structure of the PG-SGA. In terms of the internal and external consistency, the PG-SGA demonstrated intra-class correlation coefficients (ICC) up to 0.987. Alternative form validity was also demonstrated between Box 4 of the PG-SGA and the Karnofsky Performance Status score, with excellent external consistency (r = 0.972, P < 0.001). The construct validity was supported, and selected questionnaire dimensions were evident in the principal component analysis. Significant Spearman correlations (P < 0.001) were demonstrated. The Chinese version of the PG-SGA demonstrated significant reliability and sufficient exploratory properties to support its validity. It seems to be a valid tool that can be used to access the nutritional status of Chinese lung cancer patients. The validity of the PG-SGA in Chinese cancer patients warrants further investigation in other cancer types.展开更多
Purpose Malnutrition is severe among gastric cancer patients in China. While the Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used nutritional assessment tool, the validation for Chinese patient...Purpose Malnutrition is severe among gastric cancer patients in China. While the Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used nutritional assessment tool, the validation for Chinese patients with gastric cancer has not been performed yet. The aim of this research is to validate the Chinese version of the PGSGA in Chinese gastric cancer patients by conducting analyses of nutrition screening and assessment data. Methods Two thousand consecutive adult patients with gastric cancer were included in this observational, cross-sectional study in several tertiary hospitals in China. A survey was made among those patients, which included several questionnaires and some anthropometric parameters. We calculated the parameters to validate the use of PG-SGA categorizing the nutritional status of gastric cancer patients. Then we performed statistical analysis to evaluate the internal consistency, external consistency, and construct validity. Results This study verified the ability of the PG-SGA to differentiate gastric cancer patients into different nutritional groups. The confirmatory factor analysis verified the original four-factor structure of the PG-SGA. The internal and external consistency was measured by a concordance analysis which showed an intraclass correlation coefficients (ICC) of 0.987. The correlations of the Box 4 score with the Karnofsky performance status score demonstrated alternative form validity with good external consistency (Pearson, r = 0.643, P < 0.001). All three anthropometric dimensions of the PG-SGA were supported by principal component analysis. Spearman correlations (P < 0.001) were significant in the majority of tests. Conclusion The Chinese version of the PG-SGA is a valid tool to access the patients’ nutritional status for Chinese gastric patients.展开更多
Increasing research suggests that cancer is a metabolic disease.During tumor development,cancer cells increase their biosynthetic and bioenergetic demands to maintain tumor cell proliferation and metastasis.The focus ...Increasing research suggests that cancer is a metabolic disease.During tumor development,cancer cells increase their biosynthetic and bioenergetic demands to maintain tumor cell proliferation and metastasis.The focus of research on this topic has been on the metabolism of the primary tumor,while metabolic adjustments during primary tumor growth/progression and metastatic processes have not been extensively investigated.The current evidence indicates that the metabolism during tumor development is dynamic.Moreover,emerging data suggest that,once the tumor cells leave their primary sites,they may show different metabolic features distinct from the primary tumor,enabling them to successfully survive and metastasize.In this review,we summarize how this metabolic flexibility occurs during the growth of the primary tumor and the metastatic process,and also explore how metabolic adaptation is influenced by the microenvironments of the tumor cells.We hope that this review will provide inspiration and guidance for future research on tumor metabolism.展开更多
Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,lea...Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.展开更多
Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies ...Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).展开更多
For the affiliation information,the affiliation for author Feixue Wang should be Department of GI Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,...For the affiliation information,the affiliation for author Feixue Wang should be Department of GI Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin Medical University,Tianjin 300060,China.展开更多
Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL...Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods: The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results: The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage al had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score(49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer(54.2 ± 12.3) and pancreatic cancer(54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties(35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage Ⅲ/Ⅳ reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.Conclusions: There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.展开更多
Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and o...Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.展开更多
The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evalua...The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.展开更多
Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associ...Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.展开更多
The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase I...The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.展开更多
Peroxisome proliferator-activated receptor gamma （PPAR）,） coactivator-1 alpha （PGC-1α） coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the rol...Peroxisome proliferator-activated receptor gamma （PPAR）,） coactivator-1 alpha （PGC-1α） coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1α in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1α mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC- 1α expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1α in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1α dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PG-C- 1 α-induced apoptosis was partially, but not completely, blocked by PPAR）, antagonist （GW9662）, and suppression of PPAR）, expression by siRNA also inhibited PGC-1α-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1α exerted its effect through a PPARγ-dependent pathway. Our findings indicated that PGC-1α was involved in the apoptotic signal transduction pathways and downregulation of PGC-1α may be a key point in promoting epithelial ovarian cancer growth and progression.展开更多
AIM： To investigate the anticancer activity of a chinese medical mixture, WRCP （warming and relieving Cold Phlegm）, on hepatocarcinoma Bel-7402 cells. METHODS： Fingerprints of WRCP, which were composed of aqueous ...AIM： To investigate the anticancer activity of a chinese medical mixture, WRCP （warming and relieving Cold Phlegm）, on hepatocarcinoma Bel-7402 cells. METHODS： Fingerprints of WRCP, which were composed of aqueous extracts of Aconitum carmichae/i, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Gdenther, and aconitine, which could be isolated from Aconitum carmichaeli and have the potential toxicity, were identified by high pressure liquid chromatography. Bel-7402 cells were grown in the presence of WRCP, As203 or all-trans-retinoic acid （ATRA）. Cell proliferation and viability were determined by trypan blue stain. Apoptosis and cell cycle of Bel-7402 cells were detected by flow cytometry. Morphologic and ultrastructural variations were determined under optic and electronic microscopy. The secretion of alpha-fetoprotein and albumin was detected by radioimmunoassay. RESULTS： The average quality of aconitine is 1.15：1： 0.10 μg per 7.5 g extracts. WRCP could suppress the proliferation and viability of Bel-7402 cells. The percentage of apoptosis cells and S phase cells increased on WRCP-treated cells. Treated with WRCP, Bel-7402 cells showed ultrastructural features of differentiation. The alpha-fetoprotein secretion decreased while the albumin secretion increased （P 〈 0.001, P 〈 0.001, respectively） markedly in WRCP-treated cells. CONCLUSION： WRCP can affect the proliferation, differentiation and apoptosis of Bel-7402 cells. It can arrest cells in S phase and has strong cytotoxicity to Bel-7402 cells.展开更多
Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, w...Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal展开更多
Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipo...Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer(GC)-associated adipocytes.Methods:Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ,C/EPBα,PPARγ,and UCP1 in adipose mesenchymal stem cells(A-MSCs)to evaluate the function of exosomal miR-155.BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results:Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets.Similarly,A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression(P<0.05).Mechanistically,exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ,accompanied by downregulated C/EPBαand PPARγand upregulated UCP1(P<0.05).Moreover,overexpression of miR-155 in GC exosomes improved CAC in vivo,which was characterized by fat loss,suppressed expressions of C/EPBβ,C/EPBα,and PPARγin A-MSCs,and high expression of UCP1(P<0.05).Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions:GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβof A-MSCs,which played a crucial role in CAC.展开更多
BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Niv...BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.展开更多
基金Supported by CAMS Innovation Fund for Medical Sciences CIFMS,No.2023-I2M-3-012.
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase III clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.
基金supported by grants from the National Natural Science Foundation of China(Nos.82072664,81974374,82173125,82103677).
文摘Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.
文摘The prevalence of malnutrition is high among oncology patients in China. Although the Patient- Generated Subjective Global Assessment (PG-SGA) is widely recognized as an important nutritional assessment tool, it has not been validated for Chinese cancer patients. The purpose of this study was to conduct an analysis of nutrition screening and assessment data to validate the Chinese version of the PG-SGA in Chinese patients with lung cancer. This was an observational, cross-sectional study of 2,000 consecutive adult patients with lung cancer treated at several tertiary hospitals in China. Anthropometric and patient descriptive data were collected. The PG-SGA generated a score for the nutritional risk and a global rating for the nutritional status. The internal consistency, external consistency, and construct validity were evaluated, and a known-groups comparison and principal component analyses were conducted to evaluate the reliability and validity of the PG-SGA. The known-groups comparison demonstrated the ability of the PG-SGA to differentiate lung cancer patients of different nutritional and body mass index (BMI) groups. A confirmatory factor analysis supported the original four-factor structure of the PG-SGA. In terms of the internal and external consistency, the PG-SGA demonstrated intra-class correlation coefficients (ICC) up to 0.987. Alternative form validity was also demonstrated between Box 4 of the PG-SGA and the Karnofsky Performance Status score, with excellent external consistency (r = 0.972, P < 0.001). The construct validity was supported, and selected questionnaire dimensions were evident in the principal component analysis. Significant Spearman correlations (P < 0.001) were demonstrated. The Chinese version of the PG-SGA demonstrated significant reliability and sufficient exploratory properties to support its validity. It seems to be a valid tool that can be used to access the nutritional status of Chinese lung cancer patients. The validity of the PG-SGA in Chinese cancer patients warrants further investigation in other cancer types.
文摘Purpose Malnutrition is severe among gastric cancer patients in China. While the Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used nutritional assessment tool, the validation for Chinese patients with gastric cancer has not been performed yet. The aim of this research is to validate the Chinese version of the PGSGA in Chinese gastric cancer patients by conducting analyses of nutrition screening and assessment data. Methods Two thousand consecutive adult patients with gastric cancer were included in this observational, cross-sectional study in several tertiary hospitals in China. A survey was made among those patients, which included several questionnaires and some anthropometric parameters. We calculated the parameters to validate the use of PG-SGA categorizing the nutritional status of gastric cancer patients. Then we performed statistical analysis to evaluate the internal consistency, external consistency, and construct validity. Results This study verified the ability of the PG-SGA to differentiate gastric cancer patients into different nutritional groups. The confirmatory factor analysis verified the original four-factor structure of the PG-SGA. The internal and external consistency was measured by a concordance analysis which showed an intraclass correlation coefficients (ICC) of 0.987. The correlations of the Box 4 score with the Karnofsky performance status score demonstrated alternative form validity with good external consistency (Pearson, r = 0.643, P < 0.001). All three anthropometric dimensions of the PG-SGA were supported by principal component analysis. Spearman correlations (P < 0.001) were significant in the majority of tests. Conclusion The Chinese version of the PG-SGA is a valid tool to access the patients’ nutritional status for Chinese gastric patients.
文摘Increasing research suggests that cancer is a metabolic disease.During tumor development,cancer cells increase their biosynthetic and bioenergetic demands to maintain tumor cell proliferation and metastasis.The focus of research on this topic has been on the metabolism of the primary tumor,while metabolic adjustments during primary tumor growth/progression and metastatic processes have not been extensively investigated.The current evidence indicates that the metabolism during tumor development is dynamic.Moreover,emerging data suggest that,once the tumor cells leave their primary sites,they may show different metabolic features distinct from the primary tumor,enabling them to successfully survive and metastasize.In this review,we summarize how this metabolic flexibility occurs during the growth of the primary tumor and the metastatic process,and also explore how metabolic adaptation is influenced by the microenvironments of the tumor cells.We hope that this review will provide inspiration and guidance for future research on tumor metabolism.
基金grants from the National Science Foundation of China(Nos.82173125,81974374,82072664,82103677)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A)The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(2020KJ127).
文摘Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)National Natural Science Foundation of China(Grant No.82103677)National Science and Technology Major Projects of China(Grant No.2019ZX09732-001)。
文摘Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).
文摘For the affiliation information,the affiliation for author Feixue Wang should be Department of GI Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin Medical University,Tianjin 300060,China.
基金supported by the National KeyResearch and Development Program(No.2022YFC2009600 andNo.2022YFC2009601).
文摘Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods: The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results: The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage al had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score(49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer(54.2 ± 12.3) and pancreatic cancer(54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties(35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage Ⅲ/Ⅳ reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.Conclusions: There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.
基金Acknowledgments We thank Drs Fengyong Liu and Sheng Luan at UC Berkeley, USA, for their discussion and help with the writing of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （no. 30225037, 30471991, 30570731）, National Basic Research Program of China （973 Program） （no. 2006CB503909, 2004CB518603）, the ＂111＂ Project, and the Natural Science Foundation of Jiangsu Province （no. BK2004082, BK2006714）.
文摘Dysregulated expression of microRNAs （miRNAs） in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
文摘The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.
基金supported by grants from the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs(Grant Nos.18ZX09201-015 and 2017ZX09304015)the Innovation Fund for Medical Sciences of the Chinese Academy of Medical Sciences(Grant No.CIFMS,2016-I2M-1-001)。
文摘Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.
文摘The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30225037, 30400538, 30471991,30570731）；the 973 Program of China （No. 2006CB503909, 2004CB518603）；the ＂111＂ Project, and the Natural Science Foundation of Jiangsu Province （No. BK2004082, BK2006714）.
文摘Peroxisome proliferator-activated receptor gamma （PPAR）,） coactivator-1 alpha （PGC-1α） coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1α in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1α mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC- 1α expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1α in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1α dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PG-C- 1 α-induced apoptosis was partially, but not completely, blocked by PPAR）, antagonist （GW9662）, and suppression of PPAR）, expression by siRNA also inhibited PGC-1α-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1α exerted its effect through a PPARγ-dependent pathway. Our findings indicated that PGC-1α was involved in the apoptotic signal transduction pathways and downregulation of PGC-1α may be a key point in promoting epithelial ovarian cancer growth and progression.
文摘AIM： To investigate the anticancer activity of a chinese medical mixture, WRCP （warming and relieving Cold Phlegm）, on hepatocarcinoma Bel-7402 cells. METHODS： Fingerprints of WRCP, which were composed of aqueous extracts of Aconitum carmichae/i, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng and Gekko swinhonis Gdenther, and aconitine, which could be isolated from Aconitum carmichaeli and have the potential toxicity, were identified by high pressure liquid chromatography. Bel-7402 cells were grown in the presence of WRCP, As203 or all-trans-retinoic acid （ATRA）. Cell proliferation and viability were determined by trypan blue stain. Apoptosis and cell cycle of Bel-7402 cells were detected by flow cytometry. Morphologic and ultrastructural variations were determined under optic and electronic microscopy. The secretion of alpha-fetoprotein and albumin was detected by radioimmunoassay. RESULTS： The average quality of aconitine is 1.15：1： 0.10 μg per 7.5 g extracts. WRCP could suppress the proliferation and viability of Bel-7402 cells. The percentage of apoptosis cells and S phase cells increased on WRCP-treated cells. Treated with WRCP, Bel-7402 cells showed ultrastructural features of differentiation. The alpha-fetoprotein secretion decreased while the albumin secretion increased （P 〈 0.001, P 〈 0.001, respectively） markedly in WRCP-treated cells. CONCLUSION： WRCP can affect the proliferation, differentiation and apoptosis of Bel-7402 cells. It can arrest cells in S phase and has strong cytotoxicity to Bel-7402 cells.
文摘Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal
基金supported by a grant from National Natural Science Foundation of China(Grant Nos.82072664,81772629,81802363,81702431,81702437,81772843,81974374).
文摘Objective:The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia(CAC)by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer(GC)-associated adipocytes.Methods:Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ,C/EPBα,PPARγ,and UCP1 in adipose mesenchymal stem cells(A-MSCs)to evaluate the function of exosomal miR-155.BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.Results:Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets.Similarly,A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression(P<0.05).Mechanistically,exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ,accompanied by downregulated C/EPBαand PPARγand upregulated UCP1(P<0.05).Moreover,overexpression of miR-155 in GC exosomes improved CAC in vivo,which was characterized by fat loss,suppressed expressions of C/EPBβ,C/EPBα,and PPARγin A-MSCs,and high expression of UCP1(P<0.05).Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.Conclusions:GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβof A-MSCs,which played a crucial role in CAC.
基金Supported by Chinese Research Hospital Association,No.Y2019FH-DTCC-SC3。
文摘BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.
