Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in pati...Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.展开更多
AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcino...AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.展开更多
There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunothe...There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunotherapy with checkpoint inhibitors has revolutionized the treatment of urothelial carcinoma,unfortunately,only a minority of patients respond to immunotherapy.Treatment options for patients who do not respond and/or progress on immunotherapy are very limited and overall prognosis remains dismal in metastatic urothelial carcinoma.The first targeted therapy targeting the fibroblast growth factor receptor(FGFR)was recently approved for bladder cancer,but it is effective only in select patients harboring the FGFR2 and FGFR 3 mutations.Antibody drug conjugates like enfortumab vedotin have shown promising activity in clinical trials.Development of novel targeted therapies remains an area of investigation and an unmet need in bladder cancer.Exploitation of androgen receptor(AR)is a potential strategy for targeted drug development in bladder cancer.A significant proportion of urothelial carcinoma patients express AR irrespective of gender.AR signaling in urothelial carcinoma has been linked to progression through multiple mechanisms,including activation of human epidermal growth factor receptor-2(EGFR or HER-2)signaling and epithelial to mesenchymal transition(EMT).Furthermore,AR is enriched in the luminal papillary mRNA subtype of urothelial carcinoma and also mediates resistance to cisplatin-based chemotherapy.Preclinical evidence suggests that AR inhibition can successfully inhibit urothelial carcinoma growth as monotherapy and is synergistic with cisplatin-based chemotherapy.We review the preclinical and clinical evidence supporting the putative role of AR signaling in urothelial carcinoma pathogenesis,progression and its role as a novel therapeutic target and future directions.展开更多
Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment...Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment. It has been reported that in vitro and in vivo hyperthermia enhanced the cytotoxic effect of certain anticancer drugs. However, this enhancement varies, depending on the drug used and the scheduling of treatments. Thus, the combination effect of chemotherapy and hyperthermia remains unclear. In this study, we aimed to investigate whether concurrent exposure of human hepatocellular carcinoma cells SMMC-7721 to chemotherapeutic agents andhyperthermia could increase anticancer effects. Methods ： Two chemotherapeutic agents, cisplatin and hydroxycamptothecin, were applied. The MTT assay was performed to evaluate the growth inhibition of SMMC-7721 induced by anticancer drugs with and without hyperthermia. Flow cytometric analysis was used for the assessment of apoptosis after treatments. Results： The percentages of growth inhibition of SMMC-7721 induced by cisplatin （10μg/ml） alone, hydroxycamptothecin （1μg/ml）alone, hyperthermia alone, cisplatin and hyperthermia, hydroxycamptothecin and hyperthermia, were 20.77%, 13.65%, 32.46%, 62.76%, 71.89%, respectively. The percentages of apoptosis of five treatments are 5.56%, 3.96%, 10.16%, 24.32%, 20.42%, respectively. Conclusion： While both hyperthermia and anticancer drugs can individually induce apoptosis and anti-proliferation effect, the combination of the two treatments induce significantly higher apoptosis and cytotoxicity than hyperthermia or anticancer drugs treatment alone. These data suggest a synergistic benefit when hyperthermia and anticancer drugs used concurrently.展开更多
As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,ci...As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.展开更多
AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wa...AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wascarried out by digesting the locus specificpolymerase chain reaction amplified productswith alleles specific restriction enzymes(PCR-RFLP),i.e.,Apal Ⅰ,Bsaj Ⅰ,Hph Ⅰ,Fok Ⅰ,Mbo Ⅱ and Mnl Ⅰ.RESULTS The allele frequencies of DQA1 * 0301and DQA1 * 0102 in patients with duodenal ulcerwere significantly higher and lower respectivelythan those in healthy controls(0.40 vs 0.20,P = 0.003,mcorret = 0.024)and(0.05 vs 0.14,P = 0.012,but Pcorret】0.05),respectively.CONCLUSION DQA1 * 0301 is a susceptiblegene for duodenal ulcer in Wuhan Hans,andthere are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients andhealthy controls.展开更多
Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid...Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid)-poly(N-isopropylacrylamide)(PAA-PNIPAm) hydrogel capsules by using hydroxypropylcellulose-poly(acrylic acid)(HPC-PAA) complexes as the templates. The capsules showed a high drug loading(～280% to the weight of capsules) for Doxorubicin hydrochloride. The release of drug from the capsules was responsive to the temperature and p H of the surroundings, showing a low-rate but sustained release behavior favorable for low-toxic and long-term therapy. Together with the convenient preparation, high drug loading, dual responsivity as well as the sustained release feature, it is implied that this polymeric hydrogel capsule might be a promising candidate for new drug carriers.展开更多
Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory ca...Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O6-methylguanine-DNA methyltransferase （MGMT） promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.展开更多
Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(i...Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.展开更多
MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast canc...MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR （qRT-PCR）. Junctional adhesion molecule A （JAM-A） was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-offunction assays, and the inhibition of JAM-A by miR- 495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-4g5 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.展开更多
Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of...Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of HCC patients is still unsatisfactory due to the frequent relapse and chemoresistance.Accumulating evidence has demonstrated that liver cancer stem cells(CSCs)are critical for HCC chemoresistance and recurrence.Nevertheless,the molecular mechanisms of liver CSC regulation remain unclear,which hampers the development of the therapeutic strategy that targets liver CSCs.展开更多
Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster prot...Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in LIHC.We then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical cohorts.The detailed methods were described in the supplementary material.展开更多
Neutrophils are key mediators of the immune response and play essential roles in the development of tumors and immune evasion.Emerging studies indicate that neutrophils also play a critical role in the immunotherapy r...Neutrophils are key mediators of the immune response and play essential roles in the development of tumors and immune evasion.Emerging studies indicate that neutrophils also play a critical role in the immunotherapy resistance in cancer.In this review,firstly,we summarize the novel classification and phenotypes of neutrophils and describe the regulatory relationships between neutrophils and tumormetabolism,flora microecology,neuroendocrine and tumor therapy from a new perspective.Secondly,we review the mechanisms by which neutrophils affect drug resistance in tumor immunotherapy from the aspects of the immune microenvironment,tumor antigens,and epigenetics.Finally,we propose several promising strategies for overcoming tumor immunotherapy resistance by targeting neutrophils and provide new research ideas in this area.展开更多
Probiotics are natural systems bridging synthetic biology,physical biotechnology,and immunology,initiating innate and adaptive anti-tumor immune activity.We previously constructed an all-inone engineered food-grade pr...Probiotics are natural systems bridging synthetic biology,physical biotechnology,and immunology,initiating innate and adaptive anti-tumor immune activity.We previously constructed an all-inone engineered food-grade probiotic Lactococcus lactis(FOLactis)which could boost the crosstalk among different immune cells such as dendritic cells(DCs),natural killer cells,and T cells.Herein,considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines,we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides.Intranodal injection of FOLactis coated with neoantigen peptides(Ag-FOLactis)induces robust DCs presentation and neoantigen-specific cellular immunity.Notably,Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models,leading to potent inhibition of tumor growth.These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens,facilitating the development of a bio-activated platform for personalized therapy.展开更多
Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its tr...Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy.Bile acids(BAs)are products of cholesterol metabolism,that not only regulate lipid digestion and absorption,but also influence the development of HCC by modulating inflammation and metabolism.Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies.BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters,moreover,BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment.Therefore,regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy,which could be a promising treatment strategy.This review not only summarizes the roles of BA metabolism in HCC development and drug resistance,but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.展开更多
Ferroptosis is a newly form of regulated cell death,which has attracted great attention for tumor therapy.Herein,we prepared nanoscale coordination polymer Fe-NQA particles to deliver iron and NQA(vitamin K3 derivativ...Ferroptosis is a newly form of regulated cell death,which has attracted great attention for tumor therapy.Herein,we prepared nanoscale coordination polymer Fe-NQA particles to deliver iron and NQA(vitamin K3 derivative)into tumor cells,which synergistically promoted ferroptotic therapy for inhibiting tumor growth,preventing metastasis,and overcoming radioresistance.展开更多
Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells.In previous stud...Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells.In previous studies,FOLactis was designed,which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand,leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection.However,it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure.For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors,intratumoral injection is not feasible and peritumoral maybe a better choice.Herein,an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels.Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells(TEM),playing the role of artificial lymph island.Besides,administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors,resulting in an extended survival time.Therefore,these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.展开更多
To the Editor:Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.GISTs mostly occur in the stomach or small intestine among patients around 40-60 years of age,an...To the Editor:Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.GISTs mostly occur in the stomach or small intestine among patients around 40-60 years of age,and are insensitive to chemotherapy or radiotherapy.展开更多
基金Supported by National Natural Science Foundation of China,No.81220108023,No.81370064 and No.81572329Fundamental Research Funds for the Central Universities,No.20620140729+1 种基金Jiangsu Provincial Program of Medical Sciences,No.BL2012001Distinguished Young Investigator Project of Nanjing,No.JQX12002
文摘Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
基金Supported by National Natural Science Foundation of China,No.81401969Jiangsu Provincial Medical Youth Talent,No.QNRC2016043the Key Medical Science and Technology Development Project of Nanjing,No.ZKX16032
文摘AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.
文摘There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunotherapy with checkpoint inhibitors has revolutionized the treatment of urothelial carcinoma,unfortunately,only a minority of patients respond to immunotherapy.Treatment options for patients who do not respond and/or progress on immunotherapy are very limited and overall prognosis remains dismal in metastatic urothelial carcinoma.The first targeted therapy targeting the fibroblast growth factor receptor(FGFR)was recently approved for bladder cancer,but it is effective only in select patients harboring the FGFR2 and FGFR 3 mutations.Antibody drug conjugates like enfortumab vedotin have shown promising activity in clinical trials.Development of novel targeted therapies remains an area of investigation and an unmet need in bladder cancer.Exploitation of androgen receptor(AR)is a potential strategy for targeted drug development in bladder cancer.A significant proportion of urothelial carcinoma patients express AR irrespective of gender.AR signaling in urothelial carcinoma has been linked to progression through multiple mechanisms,including activation of human epidermal growth factor receptor-2(EGFR or HER-2)signaling and epithelial to mesenchymal transition(EMT).Furthermore,AR is enriched in the luminal papillary mRNA subtype of urothelial carcinoma and also mediates resistance to cisplatin-based chemotherapy.Preclinical evidence suggests that AR inhibition can successfully inhibit urothelial carcinoma growth as monotherapy and is synergistic with cisplatin-based chemotherapy.We review the preclinical and clinical evidence supporting the putative role of AR signaling in urothelial carcinoma pathogenesis,progression and its role as a novel therapeutic target and future directions.
文摘Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment. It has been reported that in vitro and in vivo hyperthermia enhanced the cytotoxic effect of certain anticancer drugs. However, this enhancement varies, depending on the drug used and the scheduling of treatments. Thus, the combination effect of chemotherapy and hyperthermia remains unclear. In this study, we aimed to investigate whether concurrent exposure of human hepatocellular carcinoma cells SMMC-7721 to chemotherapeutic agents andhyperthermia could increase anticancer effects. Methods ： Two chemotherapeutic agents, cisplatin and hydroxycamptothecin, were applied. The MTT assay was performed to evaluate the growth inhibition of SMMC-7721 induced by anticancer drugs with and without hyperthermia. Flow cytometric analysis was used for the assessment of apoptosis after treatments. Results： The percentages of growth inhibition of SMMC-7721 induced by cisplatin （10μg/ml） alone, hydroxycamptothecin （1μg/ml）alone, hyperthermia alone, cisplatin and hyperthermia, hydroxycamptothecin and hyperthermia, were 20.77%, 13.65%, 32.46%, 62.76%, 71.89%, respectively. The percentages of apoptosis of five treatments are 5.56%, 3.96%, 10.16%, 24.32%, 20.42%, respectively. Conclusion： While both hyperthermia and anticancer drugs can individually induce apoptosis and anti-proliferation effect, the combination of the two treatments induce significantly higher apoptosis and cytotoxicity than hyperthermia or anticancer drugs treatment alone. These data suggest a synergistic benefit when hyperthermia and anticancer drugs used concurrently.
基金Supported by National Natural Science Foundation of China,No.82270634.
文摘As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.
文摘AIM To study the genetic susceptibility of HLA-DQA1 alleles to duodenal ulcer in Wuhan Hans.METHODS Seventy patients with duodenalulcer and fifty healthy controls were examinedfor HLA-DQA1 genotypes.HLA-DQA1 typing wascarried out by digesting the locus specificpolymerase chain reaction amplified productswith alleles specific restriction enzymes(PCR-RFLP),i.e.,Apal Ⅰ,Bsaj Ⅰ,Hph Ⅰ,Fok Ⅰ,Mbo Ⅱ and Mnl Ⅰ.RESULTS The allele frequencies of DQA1 * 0301and DQA1 * 0102 in patients with duodenal ulcerwere significantly higher and lower respectivelythan those in healthy controls(0.40 vs 0.20,P = 0.003,mcorret = 0.024)and(0.05 vs 0.14,P = 0.012,but Pcorret】0.05),respectively.CONCLUSION DQA1 * 0301 is a susceptiblegene for duodenal ulcer in Wuhan Hans,andthere are immunogenetic differences in HLA-DQA1 locus between duodenal ulcer patients andhealthy controls.
基金financially supported by the National Natural Science Foundation of China (Grant No. 31100427, No. 81101751)the Jiangsu Province Natural Science Foundation (BK20131071)
文摘Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid)-poly(N-isopropylacrylamide)(PAA-PNIPAm) hydrogel capsules by using hydroxypropylcellulose-poly(acrylic acid)(HPC-PAA) complexes as the templates. The capsules showed a high drug loading(～280% to the weight of capsules) for Doxorubicin hydrochloride. The release of drug from the capsules was responsive to the temperature and p H of the surroundings, showing a low-rate but sustained release behavior favorable for low-toxic and long-term therapy. Together with the convenient preparation, high drug loading, dual responsivity as well as the sustained release feature, it is implied that this polymeric hydrogel capsule might be a promising candidate for new drug carriers.
文摘Peripheral T-cell lymphoma, not otherwise specified （PTCL-NOS） is a heterogeneous group of aggressive T-ce lymphomas with no treatment consensus and poor prognosis. We herein described an extraordinary refractory case of PTCL-NOS with widely involvement of subcutaneous tissue, which showed an excellent response to Semustine personal- ized chemotherapy based on the detection finding of positive O6-methylguanine-DNA methyltransferase （MGMT） promoter methylation. This is the first english report to indicate that single nitrosourea agent such as Semustine may have good efficacy and safety for widespread subcutaneous involvement of PTCL-NOS with positive MGMT promoter methylation.
基金funded by the National Natural Science Foundation of China(Grant nos.81874048,82171824,82272906)Shanghai Municipal Commission of Health and Family Planning Grant 2018ZHYL0223+6 种基金Shanghai Municipal Education Commission—Gao Feng Clinical Medicine Grant Support(Grant no.20161312)Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Municipality(Grant no.21JC1404300)Clinical Research Plan of SHDC(Grant no.SHDC2020CR1035B)Innovation Group Project of Shanghai Municipal Health Commission(Grant no.2019CXJQ03)National Key R&D Program of China(Grant no.2019YFC1315900)Project from CSCO Clinical Oncology Research Foundation(Grant no.Y-2019AZZD-0513)the Innovative Research Team of High-Level Local Universities in Shanghai(Grant no.SHSMU-ZDCX20210802).
文摘Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.
文摘MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR （qRT-PCR）. Junctional adhesion molecule A （JAM-A） was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-offunction assays, and the inhibition of JAM-A by miR- 495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-4g5 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.
基金This work was supported by the grants from the National Key Research and Developm ent Program of China 2017YFA0504503National Natural Science Foundation of China(NSFC)81972777 and 82003161+3 种基金Program of Shanghai Academ ic Research Leader(18XD1405400)Natural Science Foundation of Shanghai(20ZR145770)the Shanghai Key Laboratory of Cell Engineering(14DZ2272300)Shanghai Sailing Project(20YF1459600)from the Science and Technology Commission of Shanghai Municipality.
文摘Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of HCC patients is still unsatisfactory due to the frequent relapse and chemoresistance.Accumulating evidence has demonstrated that liver cancer stem cells(CSCs)are critical for HCC chemoresistance and recurrence.Nevertheless,the molecular mechanisms of liver CSC regulation remain unclear,which hampers the development of the therapeutic strategy that targets liver CSCs.
基金supported by the Program of the Shanghai Key Laboratory of Cell Engineering 14DZ2272300 from the Science and Technology Commission of Shanghai Municipality。
文摘Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in LIHC.We then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical cohorts.The detailed methods were described in the supplementary material.
基金National Natural Science Foundation of China,Grant/Award Numbers:82473431,82303184Innovation Program of Shanghai Municipal Education Commission,Grant/Award Number:20230548+1 种基金Shanghai Key Laboratory of Cell Engineering,Grant/Award Number:14DZ2272300Medical Discipline Construction Project of Pudong Health Committee of Shanghai,Grant/Award Number:PWYgf2021-08。
文摘Neutrophils are key mediators of the immune response and play essential roles in the development of tumors and immune evasion.Emerging studies indicate that neutrophils also play a critical role in the immunotherapy resistance in cancer.In this review,firstly,we summarize the novel classification and phenotypes of neutrophils and describe the regulatory relationships between neutrophils and tumormetabolism,flora microecology,neuroendocrine and tumor therapy from a new perspective.Secondly,we review the mechanisms by which neutrophils affect drug resistance in tumor immunotherapy from the aspects of the immune microenvironment,tumor antigens,and epigenetics.Finally,we propose several promising strategies for overcoming tumor immunotherapy resistance by targeting neutrophils and provide new research ideas in this area.
基金supported by the National Natural Science Foundation of China(81930080 and 82272811)the Fund for Distinguished Young Scholars of Jiangsu Province(BK20230001,China)the Key Project Foundation of Nanjing for the Development of Medical Technology(ID:ZKX20024,China).
文摘Probiotics are natural systems bridging synthetic biology,physical biotechnology,and immunology,initiating innate and adaptive anti-tumor immune activity.We previously constructed an all-inone engineered food-grade probiotic Lactococcus lactis(FOLactis)which could boost the crosstalk among different immune cells such as dendritic cells(DCs),natural killer cells,and T cells.Herein,considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines,we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides.Intranodal injection of FOLactis coated with neoantigen peptides(Ag-FOLactis)induces robust DCs presentation and neoantigen-specific cellular immunity.Notably,Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models,leading to potent inhibition of tumor growth.These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens,facilitating the development of a bio-activated platform for personalized therapy.
基金supported by the National Natural Science Foundation of China(grant No.82270634)Third Affiliated Hospital of Naval Medical University(grant No.tf2024yzyy01)+1 种基金Excellent Doctoral Cultivation Program of Naval Medical University,National Natural Science Foundation of China(No.82503372)China Postdoctoral Science Foundation under Grant Number(GZB20250482).
文摘Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy.Bile acids(BAs)are products of cholesterol metabolism,that not only regulate lipid digestion and absorption,but also influence the development of HCC by modulating inflammation and metabolism.Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies.BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters,moreover,BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment.Therefore,regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy,which could be a promising treatment strategy.This review not only summarizes the roles of BA metabolism in HCC development and drug resistance,but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.
基金This article was supported by The National Key Research and Development Program of China(No.2017YFA0205400)Natural Science Foundation of China(NSFC)(Nos.81603043,81872811,and 31872755)This project was also supported by the Central Fundamental Research Funds for the Central Universities.
文摘Ferroptosis is a newly form of regulated cell death,which has attracted great attention for tumor therapy.Herein,we prepared nanoscale coordination polymer Fe-NQA particles to deliver iron and NQA(vitamin K3 derivative)into tumor cells,which synergistically promoted ferroptotic therapy for inhibiting tumor growth,preventing metastasis,and overcoming radioresistance.
基金supported by the National Natural Science Foundation of China (82272811 and 81930080)the Fund for Distinguished Young Scholars of Jiangsu Province (BK20230001).
文摘Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells.In previous studies,FOLactis was designed,which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand,leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection.However,it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure.For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors,intratumoral injection is not feasible and peritumoral maybe a better choice.Herein,an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels.Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells(TEM),playing the role of artificial lymph island.Besides,administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors,resulting in an extended survival time.Therefore,these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.
基金supported by the Natural Science Foundation of China(Nos.82203178,82272852,and 82103687)Jiangsu Provincial Key Research and Development Program(No.BE2020619)+1 种基金Natural Science Foundation of Jiangsu Province(No.BK20220191)Nanjing Medical Science and Technology Development Foundation(No.YKK22086).
文摘To the Editor:Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.GISTs mostly occur in the stomach or small intestine among patients around 40-60 years of age,and are insensitive to chemotherapy or radiotherapy.
