المؤلفون: Jun Lin, Ya-Dan Li, Xiao-Li Zhang, Qiang Shu, Ming Yang, Xian Wang, Faliang Wang, Yongfang Yue, Hongchuan Jin

المصدر: Infectious Agents and Cancer, Vol 16, Iss 1, Pp 1-14 (2021)
Infectious Agents and Cancer

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, Epidemiology, M.castaneus mouse, viruses, Infectious and parasitic diseases, RC109-216, Virus, law.invention, Mouse mammary tumor virus-like virus (MMTV-LV), 03 medical and health sciences, 0302 clinical medicine, Breast cancer, law, Internal medicine, Breast Fibroadenoma, medicine, skin and connective tissue diseases, Polymerase chain reaction, RC254-282, 030304 developmental biology, 0303 health sciences, Mammary tumor, biology, business.industry, Mouse mammary tumor virus, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, biology.organism_classification, M. domesticus mouse, Infectious Diseases, 030220 oncology & carcinogenesis, House mice, M.musculus mouse, business, Research Article

الوصف: Background Despite extensive molecular epidemiological studies, the prevalence and characteristics of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) in Chinese women breast cancer are still unclear. Besides, the prevalence of MMTV-LV in women breast cancer tissue varies in different countries and its dependent factors remain inconclusive. Methods In the first part of the study, a case-control study was performed. 119 breast cancer samples (84 from Northern China and 35 from Southern China) and 50 breast fibroadenoma specimens were collected from Chinese women patients. MMTV-like env sequence and the homology to MMTV env gene were analysed by semi-nested polymerase chain reaction (PCR). We also explored the association of MMTV-LV prevalence with sample sources (Southern and Northern China) and patients’ clinicopathological characteristics. To investigate the dependent factors of the prevalence of MMTV-LV in breast cancer worldwide, a meta-analysis was conducted in the second part of the study. Results We found that the prevalence of MMTV-LV was much higher in breast cancer tissues (17.65%) than that in breast fibroadenoma specimens (4.00%) (P P P Conclusion The distribution of house mice may be a crucial environmental factor that explains the geographic differences in human breast cancer incidence. Our findings may provide a potential avenue of prevention, diagnosis and treatment for breast cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdc54b8ec67617c3ac417fa44ccffcedTest
https://doaj.org/article/2934e3f6ede04b1daee399d9bbae5386Test

المؤلفون: Lifeng Feng, Hongchuan Jin, Miaoqin Chen, Shiman Hu, Yiling Li, Ting Ting Jiang

المصدر: Signal Transduction and Targeted Therapy, Vol 5, Iss 1, Pp 1-14 (2020)
Signal Transduction and Targeted Therapy

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Cancer therapy, T-Lymphocytes, T cell, medicine.medical_treatment, Immune checkpoint inhibitors, animal diseases, lcsh:Medicine, chemical and pharmacologic phenomena, Review Article, Lymphocyte Activation, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, Immunity, Neoplasms, Nucleic Acids, Genetics, medicine, Humans, Clinical efficacy, Immune Checkpoint Inhibitors, lcsh:QH301-705.5, Immunity, Cellular, business.industry, lcsh:R, Cancer, biochemical phenomena, metabolism, and nutrition, medicine.disease, Immune checkpoint, Cancer treatment, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), 030220 oncology & carcinogenesis, Cancer research, Tumour immunology, bacteria, business

الوصف: Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::007ab9268cdffd71c0afcfe51839ae61Test
http://link.springer.com/article/10.1038/s41392-020-00347-9Test

المؤلفون: Yang Sun, Qibing Mei, Yinbo Niu, Xiao-Qiang Li, Tianle Tang, Hongchuan Jin, Yuhua Li, Ming Xie

المصدر: Journal of Ethnopharmacology. 232:47-54

مصطلحات موضوعية: Mice, Nude, Breast Neoplasms, Rhodamine 123, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nude mouse, In vivo, Drug Discovery, Animals, Humans, Medicine, Cytotoxic T cell, MTT assay, ATP Binding Cassette Transporter, Subfamily B, Member 1, Viability assay, 030304 developmental biology, P-glycoprotein, Pharmacology, Mice, Inbred BALB C, 0303 health sciences, Antibiotics, Antineoplastic, biology, business.industry, Cell growth, Saponins, biology.organism_classification, Antineoplastic Agents, Phytogenic, Tumor Burden, chemistry, Doxorubicin, Drug Resistance, Neoplasm, Trillium, 030220 oncology & carcinogenesis, MCF-7 Cells, biology.protein, Cancer research, Female, business, Phytotherapy

الوصف: Ethnopharmacological relevance The development of a multidrug-resistant (MDR) phenotype is a main obstacle to the successful treatment of breast cancer. Saponins of several herbs are considered as promising candidates for drug resistance treatment. We extracted Paris saponin VII (PS VII) from Trillium tschonoskii Maxim. and investigated whether it could sensitize chemoresistant breast cancer cells MCF-7/ADR to the cytotoxic effects of adriamycin. Materials and methods MCF-7/ADR cells were exposed to 0.5 μM PSVII plus different concentrations of adriamycin (0–100 μM). Then, MTT assay and adriamycin accumulation assay were used to assess cell proliferation and intracellular adriamycin retention. P glycoprotein levels and intracellular rhodamine 123 (Rh-123) accumulations were investigated to measure the expression and activity of P-glycoprotein. A xenograft model of nude mouse was utilized to observe the effect of PSVII in vivo. Results Treatment with PSVII influenced cell viability of MCF-7/ADR cells, as well as sensitized MCF-7/ADR cells to the cytotoxic effects of adriamycin. Moreover, PSVII significantly downregulated MDR1 expression in MCF-7/ADR cells. Intravenous administration of PSVII significantly enhanced anticancer efficacy of adriamycin to MCF-7/ADR xenograft model in nude mice. Conclusion These findings suggested a possible application of PSVII in combination with chemotherapy and/or as neo-adjuvant therapy in the treatment of MDR breast cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::722c34b0c3b949678e6b32b05520c354Test
https://doi.org/10.1016/j.jep.2018.12.018Test

المؤلفون: Ava Kwong, Man-Ting Siu, Chi-Wang Ho, Vivian Y. Shin, Jiawei Chen, Xian Wang, Isabella Cheuk, Hongchuan Jin

المصدر: Cell Death and Disease, Vol 10, Iss 4, Pp 1-10 (2019)
Cell Death & Disease

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Carcinogenesis, medicine.medical_treatment, Transplantation, Heterologous, Immunology, Apoptosis, Triple Negative Breast Neoplasms, Mice, SCID, Article, Targeted therapy, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Breast cancer, SOX2, Mice, Inbred NOD, Cancer stem cell, Cell Line, Tumor, Animals, Humans, Medicine, lcsh:QH573-671, Triple-negative breast cancer, Aged, Cell Proliferation, biology, business.industry, lcsh:Cytology, CD44, Cell Biology, Middle Aged, medicine.disease, G1 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, Transplantation, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, biology.protein, Cancer research, Female, RNA, Long Noncoding, Stem cell, business

الوصف: Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6a070f7b1eb6cca8614aa4d9c80e5ddTest
http://link.springer.com/article/10.1038/s41419-019-1513-5Test

المؤلفون: Hongchuan Jin, Jinye Xu, Zhinong Jiang, Qiqi Shi, Yu Weng, Jianwei Zhou, Xian Wang, Wenxia Xu, Xiaoling Qian, Jiaqiu Li, Lifeng Feng

المصدر: Oncotarget

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Enolase, Gene Expression, Antineoplastic Agents, Drug resistance, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Cell Line, Tumor, microRNA, Biomarkers, Tumor, medicine, Humans, cisplatin-resistance, Glycolysis, RNA, Messenger, Neoplasm Staging, Proportional Hazards Models, Cisplatin, business.industry, Tumor Suppressor Proteins, gastric cancer, Cancer, glycolysis, Prognosis, medicine.disease, Surgery, DNA-Binding Proteins, MicroRNAs, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Gene Knockdown Techniques, Phosphopyruvate Hydratase, enolase 1, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Biomarker (medicine), Female, RNA Interference, Neoplasm Grading, miRNA-22, business, Research Paper, medicine.drug

الوصف: Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7742655acba6be6e35f57bc7f934b3f7Test
https://doi.org/10.18632/oncotarget.17868Test

المؤلفون: Muchun Li, Neelum Aziz Yousafzai, Hongchuan Jin, Shilong Ying, Yiran Zhu, Huimin An, Ping Song, Wenxia Xu, Xiangtong Zhao, Zhiguo Zhang, Miaoqin Chen, Lifeng Feng, Liyuan Zhu, Shiman Hu, Xian Wang, Tingting Jiang, Lixian Yang

المصدر: Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy, Vol 4, Iss 1, Pp 1-11 (2019)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Cancer therapy, medicine.medical_treatment, lcsh:Medicine, Article, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Gefitinib, In vivo, Lysosome, Genetics, medicine, Epidermal growth factor receptor, Lung cancer, lcsh:QH301-705.5, biology, business.industry, lcsh:R, medicine.disease, In vitro, respiratory tract diseases, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), 030220 oncology & carcinogenesis, Cancer research, biology.protein, business, Tyrosine kinase, medicine.drug

الوصف: Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR TKIs) greatly improved clinical outcomes of patients with non-small cell lung cancer (NSCLC). Unfortunately, primary and acquired resistance limits their clinical benefits. To overcome such resistance, new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR. However, much less effort has been put into alternative strategies, such as targeting the intrinsic protective responses to EGFR TKIs. In this study, we found that EGFR TKIs, including gefitinib and AZD9291, impaired lysosome-dependent degradation of SQSTM1, thus compromising their anti-cancer efficiency. By accumulating in the lysosome lumen, gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity. As a result, SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance. Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo. Furthermore, a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells. Therefore, targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd65ec5964b509b808a89bbbabd065feTest
http://europepmc.org/articles/PMC6799834Test

المؤلفون: Hongchuan Jin, Bingluo Zhou, Xian Wang, Dongjun Dai, Yiming Zhong

المصدر: Oncology Letters

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, Population, Rectum, competing risk, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, education, nomograms, education.field_of_study, MAC, Proportional hazards model, business.industry, Cancer, Colorectal Mucinous Adenocarcinoma, Articles, Nomogram, medicine.disease, digestive system diseases, CRC, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Adenocarcinoma, prognosis, business

الوصف: The aim of the present study was to use a competing risk model to analyze the prognostic value of mucinous adenocarcinoma (MAC) in patients with colorectal cancer (CRC). An additional aim was to construct nomograms for estimating the 3- and 5-year overall survival (OS) and cancer specific survival (CSS) rates of patients with primary CRC with MAC. The data were extracted from the Surveillance, Epidemiology, and End Results database, and a Multivariate Cox model and competing risk model were applied to assess the OS and CSS. Cox-based and competing risk-based nomograms were constructed and internally validated by discrimination and calibration, using the bootstrapping method with 1,000 times replicates. A total of 13,035 MAC and 61,958 non-mucinous adenocarcinoma (NMAC) CRC patients were enrolled in the present study. Compared with NMAC, MAC patients had a poorer OS and CSS time in the overall population, and in subgroups that comprised metastatic, non-metastatic, male, site of sigmoid colon, rectosigmoid junction and rectal CRC cases (HR>1; P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c27ce2e983d57257ed83f7ce53a4d000Test
https://pubmed.ncbi.nlm.nih.gov/31807175Test

المؤلفون: Xiaobo Hu, Jiajun Sun, Alan Z. Zhu, Junmei Zhou, Hongchuan Jin, Xian Wang, Lin Guo, Hui Zheng, Ping Zhu, Renquan Lu, Xiang Gao, Xiaofeng Xu

المصدر: Nature Communications
Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016)

مصطلحات موضوعية: 0301 basic medicine, Proteasome Endopeptidase Complex, Science, Down-Regulation, General Physics and Astronomy, Breast Neoplasms, Drug resistance, Bioinformatics, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, In vivo, medicine, Humans, Nuclear Receptor Co-Repressor 1, Promoter Regions, Genetic, skin and connective tissue diseases, Regulation of gene expression, Multidisciplinary, COP9 Signalosome Complex, Ubiquitin, business.industry, HEK 293 cells, Estrogen Receptor alpha, Gene Amplification, Intracellular Signaling Peptides and Proteins, General Chemistry, medicine.disease, Gene Expression Regulation, Neoplastic, Isopeptidase activity, Tamoxifen, HEK293 Cells, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Proteolysis, MCF-7 Cells, Cancer research, Female, business, Corepressor, hormones, hormone substitutes, and hormone antagonists, Peptide Hydrolases, medicine.drug

الوصف: Oestrogen receptor α (ERα) antagonists are used in endocrine therapies for ERα-positive (ERα+) breast cancer patients. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. Here using integrated genomic and functional studies, we report that amplification and/or overexpression of COPS5 (CSN5/JAB1) confers resistance to tamoxifen. Amplification and overexpression of COPS5, a catalytic subunit of the COP9 complex, is present in about 9% of the ERα+ primary breast cancer and more frequently (86.7%, 26/30) in tamoxifen-refractory tumours. Overexpression of COPS5, through its isopeptidase activity, leads to ubiquitination and proteasome-mediated degradation of NCoR, a key corepressor for ERα and tamoxifen-mediated suppression of ERα target genes. Importantly, COPS5 overexpression causes tamoxifen-resistance in preclinical breast cancer models in vitro and in vivo. We also demonstrate that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine-resistant breast cancer patients.
The corepressor NCoR is required for tamoxifen-mediated ERα-dependent transcriptional repression. Here, the authors show that COPS5 confers tamoxifen-resistance through the degradation of NCOR, the recruitment of the co-activator PCAF to ERα binding sites and the subsequent ERα transcriptional activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78550151554b191df072b3158a0fd502Test
https://doi.org/10.1038/ncomms12044Test