Colorectal carcinoma(CRC) is one of the most common types of cancer worldwide and the prognosis for CRC patients with recurrence or metastasis is extremely poor. Although chemotherapy and radiation therapy can improve...Colorectal carcinoma(CRC) is one of the most common types of cancer worldwide and the prognosis for CRC patients with recurrence or metastasis is extremely poor. Although chemotherapy and radiation therapy can improve survival, there are still numerous efforts to be performed. Immunotherapy is frequently used, either alone or in combination with other therapies, for the treatment of CRC and is a safe and feasible way to improve CRC treatment. Furthermore, the significance of the immune system in the biology of CRC has been demonstrated by retrospective assessments of immune infiltrates in resected CRC tumors. Micro RNAs(mi RNAs) are short, non-coding RNAs that can regulate multiple target genes at the post-transcriptional level and play critical roles in cell proliferation, differentiation and apoptosis. Mi RNAs are required for normal immune system development and function. Nevertheless, aberrant expression of mi RNAs is often observed in various tumor types and leads to immune disorders or immune evasion. The immunomodulatory function of mi RNAs indicates that mi RNAs may ultimately be part of the portfolio of anti-cancer targets. Herein, we will review the potential roles of mi RNAs in the regulation of the immune response in CRC and then move on to discuss how to utilize different mi RNA targets to treat CRC. We also provide an overview of the major limitations and challenges of using mi RNAs as immunotherapeutic targets.展开更多
AIM： To investigate the expression of leukemia related protein 16 （LRP16）, and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients. METHODS： Immunoh...AIM： To investigate the expression of leukemia related protein 16 （LRP16）, and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients. METHODS： Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients＇ age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed. RESULTS： The expression of LRP16 was 58.6% （197/336） in gastric carcinoma and 31.7% （19/60） in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues （x^2 = 14.929, P = 0.001）. LRP16 protein expression was found in 44.1% （63/143） carcinomas at stage Ⅰ and Ⅱ, and 69.4% （134/193） carcinomas at stage Ⅲ and Ⅳ （Z2 = 21.804, P = 0.001）, and in 56.9% （182/320） of cancers without metastasis but 93.8% （15/16） of those with metastasis （2 = 8.543, P = 0.003）. The expression of LRP16 was correlated with tumor size, infiltrative depth, clinical stage, lymphatic invasion and distant metastasis （all P 〈 0.05）. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 （27.0 mo） and those without （48.0 mo, Log rank =31.644, P = 0.001）. CONCLUSION： The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.展开更多
Objective：FHL2 was previously identified to be a novel interacting factor of Id family proteins.The aim of this study was to investigate,the effects of FHL2 on Id1-mediated transcriptional regulation activity and its...Objective：FHL2 was previously identified to be a novel interacting factor of Id family proteins.The aim of this study was to investigate,the effects of FHL2 on Id1-mediated transcriptional regulation activity and its oncogenic activity in human breast cancer cells.Methods：Cell transfection was performed by Superfect reagent.Id1 stably overexpressed MCF-7 cells was cloned by G418 screening.The protein level of Id1 was detected by western blot analysis.Dual relative luciferase assays were used to measure the effect of E47-mediated transcriptional activity in MCF-7 human breast cancer cells.MTT assay was used to measure cell proliferation.Transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.Results：The basic helix-loop-helix（bHLH） factor E47-mediated transcription activity was markedly repressed by Id1 in MCF-7 cells.This Id1-mediated repression was effectively antagonized by FHL2 transduction.Overexpression of Id1 markedly promoted the proliferation rate and invasive capacity of MCF-7 cells;however,these effects induced by Id1 were significantly suppressed by overexpression of FHL2 in cells.Conclusion：FHL2 can inhibit the proliferation and invasiveness of human breast cancer cells by repressing the functional activity of Id1.These findings provide the basis for further investigating the functional roles of FHL2-Id1 signaling in the carcinogenesis and development of human breast cancer.展开更多
BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging re...BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies.However,clinical management of EC with checkpoint inhibitors requires improvement.Herein,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies.CASE SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy.Four years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic EC.Genetic testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous disease.The patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse event.The disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was continued.The patient achieved a major partial response with well-tolerated toxicities,and treatment is ongoing.CONCLUSION Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity.In this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment.These results warrant further clinical exploration.展开更多
Developing free-standing and mechanical robust membrane materials capable of superior enrichment of phosphopeptides for analyzing and identifying the specific phosphoproteome of cancer cells is significant in understa...Developing free-standing and mechanical robust membrane materials capable of superior enrichment of phosphopeptides for analyzing and identifying the specific phosphoproteome of cancer cells is significant in understanding the molecular mechanisms of cancer development and exploring new therapeutic approaches,but still a significant challenge in materials design.To this end,we firstly constructed highly flexible ZrTiO_(4) nanofibrous membranes(NFMs)with excellent mechanical stability through a cost-effective and scalable electrospinning and subsequent calcination technique.Then,to further increase the enrichment capacity of the phosphopeptide,the biomimetic TiO_(2)@ZrTiO_(4) NFMs with root hair or leaf like branch microstructure are developed by the hydrothermal post-synthetic modification of ZrTiO_(4) NFMs through growing unfurling TiO_(2) nanosheets onto the ZrTiO_(4) nanofibers.Importantly,remarkable flexibility and mechanical stability enable the resulting TiO_(2)@ZrTiO_(4) NFMs excellent practicability,while the biomimetic microstructure allows it outstanding enrichment ability of the phosphopeptide and identification ability of the specific phosphoproteins in the digest of cervical cancer cells.Specifically,6770 phosphopeptides can be enriched by TiO_(2)@ZrTiO_(4) NFMs(2205 corresponding phosphoproteins can be identified),and the value is much higher than that of ZrTiO_(4) NFMs(6399 phosphopeptides and 2132 identified phosphoproteins)and commercial high-performance TiO_(2) particles(4525 phosphopeptides and 1811 identified phosphoproteins).These results demonstrate the super ability of TiO_(2)@ZrTiO_(4) NFMs in phosphopeptide enrichment and great potential for exploring the pathogenesis of cancer.展开更多
Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients w...Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas.We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART(CART-20)cells to patients with refractory or relapsed CD20^(+)B-cell lymphoma.Eleven patients were enrolled,and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions.The overall objective response rate was 9 of 11(81.8%),with 6 complete remissions(CRs)and 3 partial remissions;no severe toxicity was observed.The median progression-free survival lasted for 46 months,and 1 patient had a 27-month continuous CR.A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed.Clinically,the lesions in special sites,specifically the spleen and testicle,were refractory to CART-20 treatment.Collectively,these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study.This study was registered at www.clinicaltrials.org as NCT01735604.展开更多
T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors(TCRs).Cancer immunotherapy,by relying on this basic recognition m...T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors(TCRs).Cancer immunotherapy,by relying on this basic recognition method,boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells.T cells genetically equipped with chimeric antigen receptors(CARs)or TCRs have shown remarkable effectiveness in treating some hematological malignancies,although the efficacy of engineered T cells in treating solid tumors is far from satisfactory.In this review,we summarize the development of genetically engineered T cells,outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy,and discuss strategies for improving the performance of these T cells in fighting cancers.展开更多
For refractory or relapsed(r/r)B-cell non-Hodgkin lymphoma(NHL),the response rates to conventional salvage chemotherapy are 27–44%.1 Chimeric antigen receptors(CARs)efficiently redirect T-cell specificity and cytotox...For refractory or relapsed(r/r)B-cell non-Hodgkin lymphoma(NHL),the response rates to conventional salvage chemotherapy are 27–44%.1 Chimeric antigen receptors(CARs)efficiently redirect T-cell specificity and cytotoxicity to cells expressing the targeted Ag in an HLA-independent manner.2 The early phase clinical trials of CART cells for(r/r)B-cell NHL have demonstrated promising results..展开更多
基金Supported by National Natural Science Foundation of ChinaNo.81272867 and No.81572914+1 种基金Beijing Nova ProgramNo.Z131107000413103
文摘Colorectal carcinoma(CRC) is one of the most common types of cancer worldwide and the prognosis for CRC patients with recurrence or metastasis is extremely poor. Although chemotherapy and radiation therapy can improve survival, there are still numerous efforts to be performed. Immunotherapy is frequently used, either alone or in combination with other therapies, for the treatment of CRC and is a safe and feasible way to improve CRC treatment. Furthermore, the significance of the immune system in the biology of CRC has been demonstrated by retrospective assessments of immune infiltrates in resected CRC tumors. Micro RNAs(mi RNAs) are short, non-coding RNAs that can regulate multiple target genes at the post-transcriptional level and play critical roles in cell proliferation, differentiation and apoptosis. Mi RNAs are required for normal immune system development and function. Nevertheless, aberrant expression of mi RNAs is often observed in various tumor types and leads to immune disorders or immune evasion. The immunomodulatory function of mi RNAs indicates that mi RNAs may ultimately be part of the portfolio of anti-cancer targets. Herein, we will review the potential roles of mi RNAs in the regulation of the immune response in CRC and then move on to discuss how to utilize different mi RNA targets to treat CRC. We also provide an overview of the major limitations and challenges of using mi RNAs as immunotherapeutic targets.
基金Supported by Grant from the Ministry of Science and Technology of China,No.2010CB912802
文摘AIM： To investigate the expression of leukemia related protein 16 （LRP16）, and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients. METHODS： Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients＇ age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed. RESULTS： The expression of LRP16 was 58.6% （197/336） in gastric carcinoma and 31.7% （19/60） in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues （x^2 = 14.929, P = 0.001）. LRP16 protein expression was found in 44.1% （63/143） carcinomas at stage Ⅰ and Ⅱ, and 69.4% （134/193） carcinomas at stage Ⅲ and Ⅳ （Z2 = 21.804, P = 0.001）, and in 56.9% （182/320） of cancers without metastasis but 93.8% （15/16） of those with metastasis （2 = 8.543, P = 0.003）. The expression of LRP16 was correlated with tumor size, infiltrative depth, clinical stage, lymphatic invasion and distant metastasis （all P 〈 0.05）. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 （27.0 mo） and those without （48.0 mo, Log rank =31.644, P = 0.001）. CONCLUSION： The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.
基金supported by the National Natural Science Foundation of China(No.30870507)supported by a grant from the Ministry of Science and Technology of China(No.2010CB912802)
文摘Objective：FHL2 was previously identified to be a novel interacting factor of Id family proteins.The aim of this study was to investigate,the effects of FHL2 on Id1-mediated transcriptional regulation activity and its oncogenic activity in human breast cancer cells.Methods：Cell transfection was performed by Superfect reagent.Id1 stably overexpressed MCF-7 cells was cloned by G418 screening.The protein level of Id1 was detected by western blot analysis.Dual relative luciferase assays were used to measure the effect of E47-mediated transcriptional activity in MCF-7 human breast cancer cells.MTT assay was used to measure cell proliferation.Transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.Results：The basic helix-loop-helix（bHLH） factor E47-mediated transcription activity was markedly repressed by Id1 in MCF-7 cells.This Id1-mediated repression was effectively antagonized by FHL2 transduction.Overexpression of Id1 markedly promoted the proliferation rate and invasive capacity of MCF-7 cells;however,these effects induced by Id1 were significantly suppressed by overexpression of FHL2 in cells.Conclusion：FHL2 can inhibit the proliferation and invasiveness of human breast cancer cells by repressing the functional activity of Id1.These findings provide the basis for further investigating the functional roles of FHL2-Id1 signaling in the carcinogenesis and development of human breast cancer.
基金Supported by the Hangzhou Health and Family Planning and Science and Technology Program,No.OO20190347。
文摘BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing rapidly.Immunotherapy using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies.However,clinical management of EC with checkpoint inhibitors requires improvement.Herein,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies.CASE SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy.Four years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic EC.Genetic testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous disease.The patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse event.The disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was continued.The patient achieved a major partial response with well-tolerated toxicities,and treatment is ongoing.CONCLUSION Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity.In this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment.These results warrant further clinical exploration.
基金supported by the National Natural Science Foundation of China(Nos.52202110,22201167)the Natural Science Foundation of Science and Technology Agency of Shanxi Province(No.20210302124654)+6 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L259)the Innovation and Entrepreneurship Training Program for College students in Shanxi Province(No.20220312)the Outstanding Young Talents of Shaanxi Universities(2019)the Scientific and Technological Plan Project of Xi’an(No.21XJZZ0012)the Key Research and Development Program of Shaanxi Province of China(No.2022SF-201)the Service Local Special Program of Education Department of Shaanxi Province(No.23JC029)the Scientific and Technological Plan Project of the Beilin District of Xi’an City(No.GX2206).
文摘Developing free-standing and mechanical robust membrane materials capable of superior enrichment of phosphopeptides for analyzing and identifying the specific phosphoproteome of cancer cells is significant in understanding the molecular mechanisms of cancer development and exploring new therapeutic approaches,but still a significant challenge in materials design.To this end,we firstly constructed highly flexible ZrTiO_(4) nanofibrous membranes(NFMs)with excellent mechanical stability through a cost-effective and scalable electrospinning and subsequent calcination technique.Then,to further increase the enrichment capacity of the phosphopeptide,the biomimetic TiO_(2)@ZrTiO_(4) NFMs with root hair or leaf like branch microstructure are developed by the hydrothermal post-synthetic modification of ZrTiO_(4) NFMs through growing unfurling TiO_(2) nanosheets onto the ZrTiO_(4) nanofibers.Importantly,remarkable flexibility and mechanical stability enable the resulting TiO_(2)@ZrTiO_(4) NFMs excellent practicability,while the biomimetic microstructure allows it outstanding enrichment ability of the phosphopeptide and identification ability of the specific phosphoproteins in the digest of cervical cancer cells.Specifically,6770 phosphopeptides can be enriched by TiO_(2)@ZrTiO_(4) NFMs(2205 corresponding phosphoproteins can be identified),and the value is much higher than that of ZrTiO_(4) NFMs(6399 phosphopeptides and 2132 identified phosphoproteins)and commercial high-performance TiO_(2) particles(4525 phosphopeptides and 1811 identified phosphoproteins).These results demonstrate the super ability of TiO_(2)@ZrTiO_(4) NFMs in phosphopeptide enrichment and great potential for exploring the pathogenesis of cancer.
基金This study was supported by the grants from the National Natural Science Foundation of China(Nos.31270820,81230061,81121004 and 81402566)was partially supported by a grant from the National Basic Science and Development Programme of China(Nos.2012CB518103,2012AA020502 and 2013BAI01B00).
文摘Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis.Chimeric Antigen Receptor(CAR)-modified T cells(CART cells)that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas.We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART(CART-20)cells to patients with refractory or relapsed CD20^(+)B-cell lymphoma.Eleven patients were enrolled,and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions.The overall objective response rate was 9 of 11(81.8%),with 6 complete remissions(CRs)and 3 partial remissions;no severe toxicity was observed.The median progression-free survival lasted for 46 months,and 1 patient had a 27-month continuous CR.A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed.Clinically,the lesions in special sites,specifically the spleen and testicle,were refractory to CART-20 treatment.Collectively,these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study.This study was registered at www.clinicaltrials.org as NCT01735604.
基金This work was supported by the National Key Research and Development Program of China(2016YFC1303403)the National Natural and Scientific Foundation of China(81572981/H1611 and 81672397/H1617)+2 种基金the National High-Tech R&D Program(863 Program2014AA020704)the Science and Technology Major Project of Sichuan Province of China(2017SZDZX0012).
文摘T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors(TCRs).Cancer immunotherapy,by relying on this basic recognition method,boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells.T cells genetically equipped with chimeric antigen receptors(CARs)or TCRs have shown remarkable effectiveness in treating some hematological malignancies,although the efficacy of engineered T cells in treating solid tumors is far from satisfactory.In this review,we summarize the development of genetically engineered T cells,outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy,and discuss strategies for improving the performance of these T cells in fighting cancers.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81402566)the grants the Science and Technology Planning Project of Beijing City(No.Z151100003915076 to WDH)the National Key Research and Development Program of China(No.2016YFC1303501 and 2016YFC1303504 to WDH).
文摘For refractory or relapsed(r/r)B-cell non-Hodgkin lymphoma(NHL),the response rates to conventional salvage chemotherapy are 27–44%.1 Chimeric antigen receptors(CARs)efficiently redirect T-cell specificity and cytotoxicity to cells expressing the targeted Ag in an HLA-independent manner.2 The early phase clinical trials of CART cells for(r/r)B-cell NHL have demonstrated promising results..
