Showing papers by "Weidong Han published in 2016"

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

SOCE and cancer: Recent progress and new perspectives.

Abstract: Ca(2+) acts as a universal and versatile second messenger in the regulation of a myriad of biological processes, including cell proliferation, differentiation, migration and apoptosis. Store-operated Ca(2+) entry (SOCE) mediated by ORAI and the stromal interaction molecule (STIM) constitutes one of the major routes of calcium entry in nonexcitable cells, in which the depletion of intracellular Ca(2+) stores triggers activation of the endoplasmic reticulum (ER)-resident Ca(2+) sensor protein STIM to gate and open the ORAI Ca(2+) channels in the plasma membrane (PM). Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, metastasis and tumor neovascularization, as well as in antitumor immunity. We summarize herein the recent advances in our understanding of the function of SOCE in various types of tumor cells, vascular endothelial cells and cells of the immune system. Finally, the therapeutic potential of SOCE inhibitors in the treatment of cancer is also discussed.

Autophagy-associated immune responses and cancer immunotherapy

Abstract: Autophagy is an evolutionarily conserved catabolic process by which cellular components are sequestered into a double-membrane vesicle and delivered to the lysosome for terminal degradation and recycling. Accumulating evidence suggests that autophagy plays a critical role in cell survival, senescence and homeostasis, and its dysregulation is associated with a variety of diseases including cancer, cardiovascular disease, neurodegeneration. Recent studies show that autophagy is also an important regulator of cell immune response. However, the mechanism by which autophagy regulates tumor immune responses remains elusive. In this review, we will describe the role of autophagy in immune regulation and summarize the possible molecular mechanisms that are currently well documented in the ability of autophagy to control cell immune response. In addition, the scientific and clinical hurdles regarding the potential role of autophagy in cancer immunotherapy will be discussed.

Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells

Abstract: // Zhao Jing 1, 2, * , Weiqiang Fei 2, * , Jichun Zhou 3, * , Lumin Zhang 2 , Liuxi Chen 1 , Xiaomin Zhang 1 , Xiao Liang 4 , Jiansheng Xie 2 , Yong Fang 1, 2 , Xinbing Sui 1, 2 , Weidong Han 1, 2 , Hongming Pan 1, 2 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 3 Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 4 Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China * These authors contributed equally to this work Correspondence to: Xinbing Sui, email: hzzju@aliyun.com Weidong Han, email: hanwd@126.com Hongming Pan, email: drpanhm@aliyun.com Keywords: salvianolic acid B, natural compound, autophagy, cell death, colorectal cancer Received: April 25, 2016 Accepted: August 13, 2016 Published: August 19, 2016 ABSTRACT Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza , is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo , suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R

Circulating tumor cells predict survival benefit from chemotherapy in patients with lung cancer.

Abstract: // Zhuo-Xuan Wu 1,* , Zhen Liu 1,* , Han-Ling Jiang 2 , Hong-Ming Pan 1 and Wei-Dong Han 1 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2 Department of Respiratory Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China * These authors have contributed equally to this work Correspondence to: Wei-Dong Han, email: // Keywords : circulating tumor cells, lung cancer, chemotherapy, tumor response, prognosis Received : May 20, 2016 Accepted : August 25, 2016 Published : August 30, 2016 Abstract Background: This meta-analysis was to explore the clinical significance of circulating tumor cells (CTCs) in predicting the tumor response to chemotherapy and prognosis of patients with lung cancer. Methods: We searched PubMed, Embase, Cochrane Database, Web of Science and reference lists of relevant articles. Our meta-analysis was performed by Stata software, version 12.0, with a random effects model. Risk ratio (RR), hazard ratio (HR) and 95% confidence intervals (CI) were used as effect measures. Results: 8 studies, including 453 patients, were eligible for analyses. We showed that the disease control rate (DCR) in CTCs-negative patients was significantly higher than CTCs-positive patients at baseline (RR = 2.56, 95%CI [1.36, 4.82], p < 0.05) and during chemotherapy (RR = 9.08, CI [3.44, 23.98], p < 0.001). Patients who converted form CTC-negative to positive or persistently positive during chemotherapy had a worse disease progression than those with CTC-positive to negative or persistently negative (RR = 8.52, CI [1.66, 43.83], p < 0.05). Detection of CTCs at baseline and during chemotherapy also indicated poor overall survival (OS) (baseline: HR = 3.43, CI [2.21, 5.33], p<0.001; during chemotherapy: HR = 3.16, CI [2.23, 4.48], p < 0.001) and progression-free survival (PFS) (baseline: HR = 3.16, 95%CI [2.23, 4.48], p < 0.001; during chemotherapy: HR = 3.78, CI [2.33, 6.13], p < 0.001). Conclusions: Detection of CTCs in peripheral blood indicates poor tumor response to chemotherapy and poor prognosis in patients with lung cancer.

Chimeric antigen receptor, gene and recombinant expression vector thereof, CARHER1-NKT cell and preparation method and application thereof

Abstract: The invention discloses a chimeric antigen receptor, a gene and a recombinant expression vector thereof, CAR20-NKT cell and a preparation method and application thereof. The chimeric antigen receptor is CD20ScFv-CD8-CD137-CD3 zeta, and comprises a rat growth hormone signal peptide, CD20ScFv, a hinge region and a transmembrane domain of CD8, an intracellular signaling structural domain of CD137 and an intracellular signaling structural domain of CD3 zeta, which are in series connection. The CAR20-NKT cells for the treatment of CD20 positive B cell lymphoma in progressive stage can effectively avoid the resistance caused by the existing drugs targeting CD20, have certain specific killing activity on cancer cells, and have certain therapeutic effect on patients with CD20 positive B cell lymphoma in progressive stage, who have been treated with multiple times of therapies (such as radiotherapy, chemotherapy and other drug symptomatic treatment) but without obvious curative effect.

Chimeric antigen receptor as well as gene and recombinant expression vector, engineered CD30-targeted NKT cell and application thereof

Abstract: The invention discloses a chimeric antigen receptor as well as a gene and a recombinant expression vector, an engineered CD30-targeted NKT cell and an application thereof. The chimeric antigen receptor is CD30ScFv-CD8-CD137-CD3 zeta, which comprises CD30ScFv, a hinge region and a transmembrane region of CD8, an intracellular signal structural domain of CD137, and an intracellular signal structural domain of CD3 zeta which are connected in series connection. The chimeric antigen receptor CD30ScFv-CD8-CD137-CD3 zeta modified NKT cell is used for treating CD30-positive Hodgkin lymphoma and non-Hodgkin's lymphoma; the chimeric antigen receptor has a good and specific killing activity for lymphoma cells, and has a certain treatment effects for CD30-positive Hodgkin lymphoma patients who have been treated for many times without obvious curative effects (such as CD30 monoclonal antibody combined with cytotoxin medicines or radio isotope therapy and the like).

Cd30-targeted chimeric antigen receptor and nkt cell and preparation method therefor and application thereof

Abstract: A chimeric antigen receptor and a gene and a recombinant expression vector thereof, and an engineered CD30-targeted NKT cell and an application thereof. The chimeric antigen receptor is CD30-ScFv-CD8-CD137-CD3ζ, which is formed by connecting CD30ScFv, a hinge region and a transmembrane region of CD8, an intracellular signal structural domain of CD137, and an intracellular signal structural domain of CD3ζ in series. When the NKT cell modified by the chimeric antigen receptor CD30-ScFv-CD8-CD137-CD3ζ treats CD30 positive hodgkin lymphoma and non-hodgkin lymphoma, very good specific cytotoxicity for lymphoma cells is achieved, and some curative effects are achieved for a CD30 positive hodgkin lymphoma patient who has been treated multiple times without achieving a significant curative effect.

Chimeric antigen receptor and gene and recombinant expression vector thereof, CAR133-NKT cells and preparation method and application of CAR133-NKT cells

Abstract: The invention belongs to the field of tumor biological products, and discloses a chimeric antigen receptor and a gene and a recombinant expression vector thereof, CAR133-NKT cells and a preparation method and an application of the CAR133-NKT cells. The chimeric antigen receptor is CD133ScFv-CD8-CD137-CD3[zeta] and comprises a rat growth hormone signal peptide, CD133ScFv, a CD8 hinge region and transmembrane region, a CD137 intracellular signal structural domain and a CD3[zeta] intracellular signal structural domain which are connected in series. When the CAR133-NKT cells are co-cultured with CD133 positive epithelial tumor cells, the CAR133-NKT cells have good specific killing activity on the CD133 positive epithelial tumor cells.

Application of CARHER1-NKT cells in preparation of preparations for treatment of HER1 positive cholangiocarcinoma in progressive stage

Abstract: The invention discloses application of CARHER1-NKT cells in the preparation of preparations for the treatment of HER1 positive cholangiocarcinoma in progressive stage. CARHER1-NKT cells are NKT cells modified by a chimeric antigen receptor HER1ScFv-CD8-CD137-CD3 zeta; the chimeric antigen receptor HER1ScFv-CD8-CD137-CD3 zeta comprises a rat growth hormone signal peptide, HER1ScFv, a hinge area and a transmembrane domain of CD8, an intracellular signal structural domain of CD137 and an intracellular signal structural domain of CD3 zeta, which are in series connection. The CARHER1-NKT cells for the treatment of HER1 positive cholangiocarcinoma in progressive stage can effectively avoid the drug resistance caused by the existing drugs targeting HER1, have certain specific killing activity on cholangiocarcinoma cells, and certain therapeutic effect on patients with HER1 positive cholangiocarcinoma in progressive stage.