In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-...In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。展开更多
Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most c...Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstaysof current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.展开更多
Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and d...Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.展开更多
Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer ste...Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT.Furthermore,microRNAs(miRNAs)play a pivotal role in the regulation of EMT phenotype,as a result,some miRNAs impact cancer stemness and drug resistance.Therefore,understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment.In this review,we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells.Then,we reviewed the interaction between EMT-associated miRNAs and the drugresistant complex signaling pathways of multiple cancers including lung cancer,gastric cancer,gynecologic cancer,breast cancer,liver cancer,colorectal cancer,pancreatic cancer,esophageal cancer,and nasopharyngeal cancer.We finally discussed the relationship between EMT,cancer stemness,and drug resistance,as well as looked forward to the potential applications of miRNA therapy for malignant tumors.展开更多
MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in b...MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.展开更多
AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.T...AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%展开更多
The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established hu...The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methyla-tion-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.展开更多
A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-...A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.展开更多
Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells....Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81871865Collaborative Innovation Program of Shanghai Municipal Health Commission,Grant/Award Number:2020CXJQ02Science and Technology Innovation Action Plan Project of Shanghai Municipal Science and Technology Commission,Grant/Award Numbers:19411950300,19411950301。
文摘In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。
文摘Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstaysof current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.
文摘Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.
基金supported by grants from the National Natural Science Foundation of China(81673760 and 81874397).
文摘Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT.Furthermore,microRNAs(miRNAs)play a pivotal role in the regulation of EMT phenotype,as a result,some miRNAs impact cancer stemness and drug resistance.Therefore,understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment.In this review,we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells.Then,we reviewed the interaction between EMT-associated miRNAs and the drugresistant complex signaling pathways of multiple cancers including lung cancer,gastric cancer,gynecologic cancer,breast cancer,liver cancer,colorectal cancer,pancreatic cancer,esophageal cancer,and nasopharyngeal cancer.We finally discussed the relationship between EMT,cancer stemness,and drug resistance,as well as looked forward to the potential applications of miRNA therapy for malignant tumors.
文摘MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.
基金Supported by Medical University of Lublin,Scientific Research Grant
文摘AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%
基金This work was supported in part by National Natural Science Foundation of China(No.30170413)the Foundation for Jing Yuan FANG of National Excellent Doctoral Dissertation of China(No.199946)the Foundation of Shanghai Education Committee(Shuguang Plan,No.02SG45).
文摘The aim of this study is to assess the effects of DNA methylation and historic acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methyla-tion-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.
文摘A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
基金the financial support from National Natural Science Foundation of China (81773911, 81690263, 81673372, and 81361140344)National Basin Research Program of China (2013CB 932500)Development Project of Shanghai Peak Disciplines– Integrated Medicine (No. 20150407)
文摘Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.
