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Pancreatic Neoplasms: HELP
Articles by Ming Zhao
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, Min Zhao wrote the following 30 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Short- and long-term outcomes after enucleation of pancreatic tumors: An evidence-based assessment. 2016

Zhou, Yanming / Zhao, Min / Wu, Lupeng / Ye, Feng / Si, Xiaoying. ·Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address: zhouymsxy@sina.cn. · Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China. ·Pancreatology · Pubmed #27423534.

ABSTRACT: BACKGROUND AND OBJECTIVE: Enucleation of pancreatic tumors is rarely performed. The aim of this study was to evaluate the published evidence for its short- and long-term outcomes. METHODS: PubMed (MEDLINE) and EMBASE databases were searched from 1990 to March 2016. Studies including at least ten patients who underwent enucleation of pancreatic lesions were included. Data on the outcomes were synthesized and meta-analyzed where appropriate. RESULTS: Twenty-seven studies involving 1316 patients were included in the systematic review. The postoperative mortality was 0.3%, and the postoperative morbidity was 50.3%, mainly represented by pancreatic fistula (38.1%). Endocrine insufficiency, exocrine insufficiency and tumor recurrence was observed in 2.4%, 1.1% and 2.3% of the patients respectively. Compared with typical resection, the operation time, blood loss, length of hospital stay, and the incidence of endocrine and exocrine insufficiency were all significantly reduced after enucleation. The occurrence of pancreatic fistula was significantly higher in enucleation group, but overall morbidity, the reoperation rate and mortality were comparable between the two groups. There was no significant difference in disease recurrence between the two groups. Compared with central pancreatectomy, enucleation had a shorter operation time, lower blood loss, less morbidity, and better pancreatic function. Compared with open enucleation, minimally invasive enucleation had a shorter operation time and a shorter length of hospital stay. CONCLUSIONS: Enucleation is an appropriate surgical procedure in selected patients with benign or low-malignant lesions of the pancreas. The benefits of minimally invasive approach need to be validated in further investigations with larger groups of patients.

2 Clinical Trial Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer. 2012

Laheru, Daniel / Shah, Preeti / Rajeshkumar, N V / McAllister, Florencia / Taylor, Gretchen / Goldsweig, Howard / Le, Dung T / Donehower, Ross / Jimeno, Antonio / Linden, Sheila / Zhao, Ming / Song, Dongweon / Rudek, Michelle A / Hidalgo, Manuel. ·Department of Medical Oncology, Skip Viragh Center for Pancreatic Cancer Research and Patient Care, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting- Blaustein Cancer Research Building, Room 4M09, Baltimore, MD 21231, USA. laherda@jhmi.edu ·Invest New Drugs · Pubmed #22547163.

ABSTRACT: PURPOSE: S-trans,trans-Farnesylthiosalicylic Acid (FTS, salirasib) inhibits Ras-dependent cell growth by dislodging all isoforms of Ras, including mutant Ras, from the plasma membrane. This study evaluated the activity, safety, and toxicity of salirasib in preclinical models and patients with metastatic pancreatic adenocarcinoma (PDA). PATIENTS AND METHODS: In the preclinical study, salirasib was tested, alone and in combination with gemcitabine, in patient derived xenografts (PDX) of PDA. In the clinical study, treatment-naïve patients with advanced, metastatic PDA were treated with a standard dose schedule of gemcitabine and salirasib 200-800 mg orally (PO) twice daily (bid) for 21 days every 28 days. Tissue from preclinical models and patients' biopsies were collected pre-treatment and on Cycle (C) 1, Day (D) 9 to characterize the effect of gemcitabine and salirasib on activated Ras protein levels. Plasma samples for pharmacokinetics were collected for salirasib administered alone and in combination. RESULTS: Salirasib inhibited the growth of 2/14 PDX models of PDA and modulated Ras signaling in these tumors. Nineteen patients were enrolled. No DLTs occurred. Common adverse events included hematologic and gastrointestinal toxicities and fatigue. The median overall survival was 6.2 months and the 1 year survival 37 %. In 2 patients in whom paired tissue biopsies were available, Ras and KRas protein levels were decreased on C1D9. Salirasib exposure was not altered by gemcitabine and did not correlate with PD outcomes. CONCLUSION: The combination of gemcitabine and salirasib appears well-tolerated, with no alteration of salirasib exposure, and exerted clinical and PD activity in PDA.

3 Article Clinicopathological features and prognostic factors of solid pseudopapillary neoplasms of pancreas. 2019

Wu, Jian-Hui / Tian, Xiu-Yun / Liu, Bo-Nan / Li, Cheng-Peng / Zhao, Min / Hao, Chun-Yi. ·Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China. · Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China. ·Pak J Pharm Sci · Pubmed #30852485.

ABSTRACT: .To explore the clinicopathological features of solid pseudopapillary neoplasm (SPN) of pancreas and to analyze the related factors of SPNs with aggressive behavior. Clinical data of SPN patients admitted in the Single Center of Peking University Cancer Hospital from January 2007 to September 2017 were retrospectively analyzed. The correlations of clinicopathological features with aggressive SPNs and distant metastasis after curative resection were analyzed using univariate analysis. Twelve of the total 54 SPN patients were diagnosed as aggressive SPNs. Univariate analysis suggested clinical features had no correlations with aggressive SPNs. Patients were followed up for an average of 5.0 years, four of them developed distant metastases. Univariate analysis indicated that distant metastasis of SPNs was correlated with the aggressive behaviors (P=0.031). Moreover, vessels invasion (VI) and Ki-67>4% (P=0.012) were the independent risk factors of distant metastasis of SPNs. The aggressive SPNs, especially VI and Ki-67>4% are the independent factors correlated with distant metastases after SPNs surgery.

4 Article T cell receptor β-chain repertoire analysis of tumor-infiltrating lymphocytes in pancreatic cancer. 2019

Cui, Can / Tian, Xiuyun / Wu, Jianhui / Zhang, Chaoting / Tan, Qin / Guan, Xiaoya / Dong, Bin / Zhao, Min / Lu, Zheming / Hao, Chunyi. ·Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, China. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, China. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China. ·Cancer Sci · Pubmed #30426614.

ABSTRACT: Pancreatic cancer is lethal due to lack of perceptible symptoms and effective treatment methods. Immunotherapy may provide promising therapeutic choices for malignant tumors like pancreatic cancer. Tumor-infiltrating lymphocytes (TIL) in tumor mesenchyme could recognize peptide antigens presented on the surface of tumor cells. The present study aimed to test the relationship between the T cell receptor (TCR) β repertoire of the tumor and peripheral blood, and also to investigate the intra-tumor spatial heterogeneity of the TCR β repertoire in pancreatic cancer. To the best of our knowledge, this is the first study to evaluate the clonal composition of TCR β repertoire in TIL across the spatial extent of pancreatic cancer. In this study, we studied 5 patients who were diagnosed with primary pancreatic cancer. Ultra-deep sequencing was used to assess the rearrangement of the TCR β-chain (TCR β) gene. HE staining and immunohistochemistry of CD3, CD4, CD8 and HLA class I were used to show histopathology and immune conditions macroscopically. TIL repertoire showed that different regions of the same tumor showed a greater number of repertoire overlaps between each other than between peripheral blood, which suggested that T cell clones in pancreatic cancer might be quite different from those in peripheral blood. In contrast, intra-tumoral TCR β repertoires were spatially homogeneous between different regions of a single tumor tissue. Based on these results, we speculated that the cellular adaptive immune response in pancreatic cancer was spatially homogeneous; this may pave the way for immunotherapy for the treatment of pancreatic cancer patients.

5 Article Association of Pioglitazone with Increased Risk of Prostate Cancer and Pancreatic Cancer: A Functional Network Study. 2018

Wen, Weiheng / Wu, Peili / Gong, Jinru / Zhao, Min / Zhang, Zhen / Chen, Rongping / Chen, Hong / Sun, Jia. ·Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China. · State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. · Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China. chenhong123@smu.edu.cn. · Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China. sunjia@smu.edu.cn. ·Diabetes Ther · Pubmed #30255424.

ABSTRACT: INTRODUCTION: The question of whether pioglitazone, an antidiabetic drug, increases the risk of cancer has been debated for some time. Recent studies have shown that pioglitazone use can increase the risk of prostate cancer as well as pancreatic cancer. However, it is unclear whether pioglitazone is a causal risk factor for these cancers. METHODS: In this study, we aimed to explore the direct targets of pioglitazone and genes associated with this drug by querying open platforms in order to construct a biological function network, and then to further evaluate the relationships of pioglitazone with prostate cancer and pancreatic cancer. RESULTS: We first tested our hypothesis using DrugBank and STRING. We identified four direct targets of pioglitazone and 50 pioglitazone-associated genes, which were then selected for KEGG pathway analysis using STRING and WebGestalt. This analysis generated the top 25 KEGG pathways, among which four pathways were related to site-specific cancers, including prostate cancer and pancreatic cancer. Finally, a genomic study using cBioPortal indicated that genomic alterations of two gene sets related to the prostate cancer and pancreatic cancer pathways, respectively, are associated with the acceleration of carcinogenesis. CONCLUSIONS: Pioglitazone is likely to be a causal risk factor for prostate cancer and pancreatic cancer, so this drug should be used with caution. The present research also demonstrates the use of biological function network analysis to effectively explore drug interactions and drug safety profiles.

6 Article Tumor targeting Salmonella typhimurium A1-R in combination with gemcitabine (GEM) regresses partially GEM-resistant pancreatic cancer patient-derived orthotopic xenograft (PDOX) nude mouse models. 2018

Kawaguchi, Kei / Miyake, Kentaro / Zhao, Ming / Kiyuna, Tasuku / Igarashi, Kentaro / Miyake, Masuyo / Higuchi, Takashi / Oshiro, Hiromichi / Bouvet, Michael / Unno, Michiaki / Hoffman, Robert M. ·a AntiCancer, Inc ., San Diego , CA , USA. · b Department of Surgery , University of California , San Diego , CA , USA. · c Department of Surgery, Graduate School of Medicine , Tohoku University , Sendai , Japan. ·Cell Cycle · Pubmed #29963961.

ABSTRACT: Gemcitabine (GEM) is first-line therapy for pancreatic cancer but has limited efficacy in most cases. Nanoparticle-albumin bound (nab)-paclitaxel is becoming first-line therapy for pancreatic cancer, but also has limited efficacy for pancreatic cancer. Our goal was to improve the treatment outcome in patient-like models of pancreatic cancer. We previously established patient-derived orthotopic xenografts (PDOX) pancreatic cancers from two patients. The pancreatic tumor was implanted orthotopically in the pancreatic tail of nude mice to establish the PDOX models. Five weeks after implantation, 50 PDOX mouse models were randomized into five groups of 10 mice for each pancreatic cancer PDOX: untreated control; GEM (100 mg/kg, i.p., once a week for 2 weeks); GEM + nab-PTX (GEM: 100 mg/kg, i.p., once a week for 2 weeks, nab-PTX: 10 mg/kg, i.v., twice a week for 2 weeks); S. typhimurium A1-R (5 × 10

7 Article Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology Combined With Automated Quantitative DNA Cytometry Can Improve the Value in the Detection of Pancreatic Malignancy. 2018

Zhao, Min / Yang, Li / Fu, Xin / Yang, Qiao / Liu, Na / Guo, Changcun / Ke, Xiaoru / Wang, Xin / Guo, Xuegang / Wu, Kaichun / Fan, Daiming / Zhang, Hongbo / Zhang, Xiaoyin. · ·Pancreas · Pubmed #29215542.

ABSTRACT: OBJECTIVES: Quantitative DNA-image cytometry (ICM) is used to diagnose malignancy via detecting changes in DNA content. We aimed to estimate the value of cytology, DNA-ICM, and their combination in diagnosing pancreatic malignancy. METHODS: One hundred twenty-one endoscopic ultrasound-guided fine-needle aspiration samples from 116 patients suspected for pancreatic malignancy were examined by cytology and DNA-ICM. Their results and the final diagnoses (malignancy or not) were collected. Diagnostic values were compared among cytology, DNA-ICM, and their combination. RESULTS: The DNA-ICM had a lower sensitivity and accuracy than cytology (64.2% vs 81.1%; 71.9% vs 85.1%). The combination of the techniques significantly improved the diagnostic accuracy compared with that of cytology or DNA-ICM alone (0.932 vs 0.905, P = 0.02; 0.932 vs 0.821, P < 0.0001). Using the Youden index, we determined that one cell with DI (DNA index) ≥2.5 is the optimal cutoff value for DNA-ICM to diagnose pancreatic malignancy. After adoption of this criterion, the sensitivity and accuracy were improved to 74.7% and 80.2% with DNA-ICM and 90.5% and 92.6% with the combined method. CONCLUSIONS: The DNA-ICM is an effective complementary method to cytology in diagnosing pancreatic malignancy. Although the diagnostic value for DNA-ICM is lower than that of cytology, an improved value was obtained after their combination.

8 Article Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8 2018

Murakami, Takashi / Hiroshima, Yukihiko / Zhang, Yong / Zhao, Ming / Kiyuna, Tasuku / Hwang, Ho Kyoung / Miyake, Kentaro / Homma, Yuki / Mori, Ryutaro / Matsuyama, Ryusei / Chishima, Takashi / Ichikawa, Yasushi / Tanaka, Kuniya / Bouvet, Michael / Endo, Itaru / Hoffman, Robert M. ·AntiCancer, Inc., San Diego, California. · Department of Surgery, University of California, San Diego, California. · Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. ·J Cell Biochem · Pubmed #28628234.

ABSTRACT: The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8

9 Article Superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic adenocarcinoma. 2017

Liu, Dao-Ning / Lv, Ang / Tian, Zhi-Hua / Tian, Xiu-Yun / Guan, Xiao-Ya / Dong, Bin / Zhao, Min / Hao, Chun-Yi. ·Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. · Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing, People's Republic of China. · Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. ·Oncotarget · Pubmed #27999192.

ABSTRACT: The aim of this study is trying to describe more details of superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, to evaluate biological and prognostic implications of tumor budding in this margin, and to provide more evidence for evaluation of R0 surgery in pancreaticoduodenectomy. 46 patients in 5-years period are included in this study. Immunochemistry and immunofluorescence are used to analyze tumor budding and epithelial-mesenchymal transition. Superior mesenteric artery margin might be described from four aspects including location, gross appearance, microscopic appearance and tumor budding. We find that 1mm rule for R1 surgery is more appropriate to predict prognosis (P = 0.009) than 0mm rule (P = 0.141). Expression of cytokeratin in tumor budding is significantly lower than primary tumor (P = 0.001), and it suggests that tumor budding may participate the procedure of epithelial-mesenchymal transition. High-grade tumor budding and decreasing cytokeratin of tumor budding correlate with distant metastasis and has negative influence on prognosis. So superior mesenteric artery margin might be not only an area that tumor cells may invade, but also a pathway for distant metastasis. It is necessary to evaluate superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic cancer.

10 Article CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression. 2016

Zheng, Biao / Ohuchida, Kenoki / Chijiiwa, Yoshiro / Zhao, Ming / Mizuuchi, Yusuke / Cui, Lin / Horioka, Kohei / Ohtsuka, Takao / Mizumoto, Kazuhiro / Oda, Yoshinao / Hashizume, Makoto / Nakamura, Masafumi / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kenoki@surg1.med.kyushu-u.ac.jp. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mizumoto@surg1.med.kyushu-u.ac.jp. · Kyushu University Hospital Cancer Center, Fukuoka, Japan. mizumoto@surg1.med.kyushu-u.ac.jp. · Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Mol Carcinog · Pubmed #26373617.

ABSTRACT: Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high-grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-κB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression. © 2015 Wiley Periodicals, Inc.

11 Article TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells. 2015

Zheng, Biao / Ohuchida, Kenoki / Cui, Lin / Zhao, Ming / Shindo, Koji / Fujiwara, Kenji / Manabe, Tatsuya / Torata, Nobuhiro / Moriyama, Taiki / Miyasaka, Yoshihiro / Ohtsuka, Takao / Takahata, Shunichi / Mizumoto, Kazuhiro / Oda, Yoshinao / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Int J Oncol · Pubmed #26035794.

ABSTRACT: The cell surface protein Transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors, and its expression on tumor cells is implicated in cancer cell metastasis and patient prognosis. The role of TM4SF1 in malignant tumors remains poorly understood, particularly in pancreatic cancer. We performed immunohistochemical staining to analyze the expression of TM4SF1 in resected pancreatic tissues and investigated the correlation between TM4SF1 expression and prognosis. The function of TM4SF1 in the invasion and migration of pancreatic cancer cells was analyzed in vitro using an RNA interference technique. In pancreatic cancer tissues, TM4SF1 expression was detected in cancer cells, and patients with high tumor levels of TM4SF1 showed longer survival times than those with low TM4SF1 levels (P=0.0332). In vitro, reduced TM4SF1 expression enhanced the migration (P<0.05) and invasion (P<0.05) of pancreatic cancer cells partially via decreased E-cadherin expression. TM4SF1 protein levels were also reduced after TGF-β1-induced epithelial-mesenchymal transition (EMT).TM4SF1 expression is associated with better prognosis in pancreatic cancer. Loss of TM4SF1 contributes to the invasion and migration of pancreatic cancer cells.

12 Article Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models. 2014

Hiroshima, Yukihiko / Zhang, Yong / Murakami, Takashi / Maawy, Ali / Miwa, Shinji / Yamamoto, Mako / Yano, Shuya / Sato, Sho / Momiyama, Masashi / Mori, Ryutaro / Matsuyama, Ryusei / Chishima, Takashi / Tanaka, Kuniya / Ichikawa, Yasushi / Bouvet, Michael / Endo, Itaru / Zhao, Ming / Hoffman, Robert M. ·AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA. Yokohama City University Graduate School of Medicine, Yokohama, Japan. · AntiCancer, Inc., San Diego, CA, USA. · Yokohama City University Graduate School of Medicine, Yokohama, Japan. · Department of Surgery, University of California San Diego, San Diego, CA, USA. · AntiCancer, Inc., San Diego, CA, USA. Department of Surgery, University of California San Diego, San Diego, CA, USA. ·Oncotarget · Pubmed #25402324.

ABSTRACT: The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.

13 Article [Intraductal carcinoma of prostate: diagnostic criteria and differential diagnosis]. 2014

Cheng, Liang / Zhao, Ming. ·E-mail: liang_cheng@yahoo.com. ·Zhonghua Bing Li Xue Za Zhi · Pubmed #24842024.

ABSTRACT: -- No abstract --

14 Article Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX). 2014

Hiroshima, Yukihiko / Zhao, Ming / Maawy, Ali / Zhang, Yong / Katz, Matthew H G / Fleming, Jason B / Uehara, Fuminari / Miwa, Shinji / Yano, Shuya / Momiyama, Masashi / Suetsugu, Atsushi / Chishima, Takashi / Tanaka, Kuniya / Bouvet, Michael / Endo, Itaru / Hoffman, Robert M. ·AntiCancer, Inc., San Diego, California; Department of Surgery, University of California, San Diego, California; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. ·J Cell Biochem · Pubmed #24435915.

ABSTRACT: The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.

15 Article Expression of glucagon-like Peptide 1 receptor and its effects on biologic behavior in pancreatic neuroendocrine tumors. 2014

Cases, Ana Ines / Ohtsuka, Takao / Fujino, Minoru / Ideno, Noboru / Kozono, Shingo / Zhao, Ming / Ohuchida, Kenoki / Aishima, Shinichi / Nomura, Masatoshi / Oda, Yoshinao / Mizumoto, Kazuhiro / Tanaka, Masao. ·From the Departments of *Surgery and Oncology, †Anatomic Pathology, and ‡Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Pancreas · Pubmed #24326362.

ABSTRACT: OBJECTIVES: Glucagon-like peptide 1 (GLP-1) interacts with its specific high-affinity receptor, glucagon-like peptide 1 receptor (GLP-1R), and induces cellular growth and inhibition of apoptosis in pancreatic β cells. The aim of this study was to investigate the significance of GLP-1R expression in pancreatic neuroendocrine tumors (PNETs). METHODS: Glucagon-like peptide 1 receptor expression was semiquantitatively evaluated by immunohistochemical staining in 50 resected PNETs, and the correlation between the GLP-1R expression and clinicopathologic features was investigated. RESULTS: There were 23 PNETs with positive expression and 27 PNETs with negative expression of GLP-1R. Positive expression of GLP-1R was more frequently observed in insulinoma than in gastrinoma and nonfunctioning tumor (P < 0.05). Although expression status of GLP-1R did not affect the prognosis of the patients with PNETs (P = 0.82), most of the metastatic sites such as lymph node and liver showed positive staining for GLP-1R (8 of 11 PNETs, 73%). CONCLUSIONS: Glucagon-like peptide 1 receptor would be a diagnostic marker of insulinoma and might become a molecular target for treatment of metastatic PNETs and hormonal regulation of insulin.

16 Article Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. 2013

Hiroshima, Yukihiko / Zhao, Ming / Zhang, Yong / Maawy, Ali / Hassanein, Mohamed K / Uehara, Fuminari / Miwa, Shinji / Yano, Shuya / Momiyama, Masashi / Suetsugu, Atsushi / Chishima, Takashi / Tanaka, Kuniya / Bouvet, Michael / Endo, Itaru / Hoffman, Robert M. ·AntiCancer, Inc; San Diego, CA USA; Department of Surgery; University of California San Diego; San Diego, CA USA; Yokohama City University Graduate School of Medicine; Yokohama, Japan. ·Cell Cycle · Pubmed #23966167.

ABSTRACT: The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC 50 values of stem-like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC 50 values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1-R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P = 0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The results of the present report indicate A1-R is a promising therapy for chemo-resistant pancreatic cancer stem-like cells.

17 Article S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells. 2013

Kozono, Shingo / Ohuchida, Kenoki / Ohtsuka, Takao / Cui, Lin / Eguchi, Daiki / Fujiwara, Kenji / Zhao, Ming / Mizumoto, Kazuhiro / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Oncol Rep · Pubmed #23900547.

ABSTRACT: Improving poor outcomes in patients with pancreatic cancer requires a greater understanding of the biological mechanisms contributing to radioresistance. We, therefore, sought to identify genes involved in the radioresistance of pancreatic cancer cells. Two pancreatic cancer cell lines, CFPAC-1 and Capan-1, were repeatedly exposed to radiation, establishing two radioresistant cell lines. Gene expression profiling using cDNA microarrays was performed to identify genes responsible for radioresistance. The levels of expression of mRNAs encoded by selected genes and their correlation with radiation dose resulting in 50% survival rate were analyzed in pancreatic cancer cell lines. The radiation dose resulting in a 50% survival rate was significantly higher in irradiated (IR) compared to parental CFPAC-1 cells (8.31 ± 0.85 Gy vs. 2.14 ± 0.04 Gy, P<0.0001), but was lower in IR compared with parental Capan-1 cells (2.66 ± 0.24 Gy vs. 2.25 ± 0.03 Gy, P=0.04). cDNA microarray analysis identified 4 genes, including S100 calcium binding protein A4 (S100A4), overexpressed and 23 genes underexpressed in the IR compared with the parental cell lines. The levels of S100A4 mRNA expression were correlated with radiation dose resulting in a 50% survival rate (Pearson's test, R2=0.81, P=0.0025). S100A4 mRNA expression may predict radioresistance of pancreatic cancer cells and may play an important role in the poor response of pancreatic cancer cells to radiation therapy.

18 Article Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice. 2013

Zhao, Min / Tang, Su-Ni / Marsh, Justin L / Shankar, Sharmila / Srivastava, Rakesh K. ·Department of Pharmacology, Toxicology and Therapeutics, and Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA. ·Cancer Lett · Pubmed #23684930.

ABSTRACT: Ellagic acid (EA) is a polyphenol found in several plants and fruits. The objectives of this study were to examine the molecular mechanisms by which EA inhibits pancreatic cancer growth in Balb C nude mice. PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA. The expression of Akt, Shh and Notch and their target gene products were measured by the immunohistochemistry and Western blot analysis. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage. EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group. EA inhibited the markers of angiogenesis (COX-2, HIF1α, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues. Furthermore, treatment of mice with EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1. EA also reversed epithelial to mesenchymal transition by up-regulating E-cadherin and inhibiting the expression of Snail, MMP-2 and MMP-9. These data suggest that EA can inhibit pancreatic cancer growth, angiogenesis and metastasis by suppressing Akt, Shh and Notch pathways. In view of the fact that EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways, our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.

19 Article Efficacy comparison of traditional Chinese medicine LQ versus gemcitabine in a mouse model of pancreatic cancer. 2013

Zhang, Lei / Wu, Chengyu / Zhang, Yong / Liu, Fang / Zhao, Ming / Bouvet, Michael / Hoffman, Robert M. ·AntiCancer, Inc., San Diego, California, USA. ·J Cell Biochem · Pubmed #23553901.

ABSTRACT: Pancreatic cancer is highly treatment-resistant and has one of the highest fatality rates of all cancers and is the fourth highest cancer killer worldwide. Novel, more effective strategies are needed to treat this disease. We report here on the use of patient-like orthotopic nude-mouse models of human metastatic pancreatic cancer to compare the traditional Chinese medicine (TCM) herbal mixture LQ to gemcitabine, which is first-line therapy for this disease, for anti-metastatic and anti-tumor activity as well as safety. The human pancreatic cancer cell line, MiaPaCa-2, labeled with red fluorescent protein (RFP), was used for the orthotopic model. LQ (gavage, 600 mg/kg/day) significantly inhibited pancreatic cancer tumor growth and metastasis, as measured by imaging, with no overt toxicity. Survival of tumor-bearing mice was also prolonged by LQ. The therapeutic efficacy of LQ is comparable with gemcitabine but with less toxicity, as indicated by a lack of body-weight loss with LQ, but not gemcitabine. The results indicate that TCM can have non-toxic efficacy against metastatic pancreatic cancer comparable to gemcitabine in a clinically-relevant orthotopic mouse model.

20 Article Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma. 2013

Mahawithitwong, Prawej / Ohuchida, Kenoki / Ikenaga, Naoki / Fujita, Hayato / Zhao, Ming / Kozono, Shingo / Shindo, Koji / Ohtsuka, Takao / Mizumoto, Kazuhiro / Tanaka, Masao. ·Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan. ·Pancreas · Pubmed #23508013.

ABSTRACT: OBJECTIVES: Kindlin-2 is a novel focal adhesion protein reported to be expressed in breast, lung, and gastric cancers. This study aimed to investigate the significance of kindlin-2 expression in pancreatic ductal adenocarcinomas (PDACs). METHODS: We performed immunohistochemical analysis on kindlin-2 on PDAC samples from 95 patients. We investigated the association between kindlin-2 expression and clinicopathological parameters of PDAC and the survival time of patients with PDAC who underwent pancreatectomy. RESULTS: Kindlin-2 was highly expressed in the peritumoral stroma of PDACs. Stromal kindlin-2 expression was related to nodal metastasis (P = 0.03). Univariate analysis showed that patients with positive kindlin-2 expression had significantly shorter survival times than those with negative kindlin-2 expression (P = 0.01). In addition, multivariate analysis revealed that kindlin-2 expression was an independent factor of poor prognosis in patients with PDAC after R0 resection (RR = 2.15; P = 0.04). CONCLUSIONS: Kindlin-2 expression in stromal components is significantly associated with poor prognosis of patients with PDAC, suggesting that kindlin-2 is a prognostic marker for patients with PDAC.

21 Article Kindlin-1 expression is involved in migration and invasion of pancreatic cancer. 2013

Mahawithitwong, Prawej / Ohuchida, Kenoki / Ikenaga, Naoki / Fujita, Hayato / Zhao, Ming / Kozono, Shingo / Shindo, Koji / Ohtsuka, Takao / Aishima, Shinichi / Mizumoto, Kazuhiro / Tanaka, Masao. ·Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ·Int J Oncol · Pubmed #23440354.

ABSTRACT: Kindlin-1 is a novel focal adhesion protein that belongs to the kindlin family. Expression of kindlin-1 has recently been reported in lung and colon cancers, but there have been no studies on its expression in pancreatic cancer. This study aimed to investigate the expression and function of kindlin-1 in pancreatic cancer. Quantitative RT-PCR of Kindlin-1 mRNA was performed in various pancreatic cancer cell lines as well as normal pancreatic epithelial cells and fibroblasts. Immunohistochemical analysis of kindlin-1 was performed for pancreatic cancer tissues. The effects of kindlin-1 on the proliferation, migration and invasion of pancreatic cancer cells were investigated using an RNA interference technique. Kindlin-1 mRNA was highly expressed in the pancreatic cancer cell lines, but only slightly expressed in normal pancreatic epithelial cells and fibroblasts. The Kindlin-1 protein was heterogeneously expressed in the cytoplasm and membrane of pancreatic cancer cells, while normal ductal epithelial cells and stromal cells showed no expression. In vitro experiments involving knockdown of kindlin-1 in AsPC-1 and KP-2 cells revealed that the migratory and invasive abilities of the cells were significantly decreased (P<0.001), while the proliferation abilities were not affected. The present findings suggest that kindlin-1 expression is involved in the progression of pancreatic cancer via enhancement of cell migration and invasion.

22 Article Efficacy of minimally invasive therapies on unresectable pancreatic cancer. 2013

Huang, Zhi-Mei / Pan, Chang-Chuan / Wu, Pei-Hong / Zhao, Ming / Li, Wang / Huang, Zi-Lin / Yi, Rui-Yang. ·Division of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. ·Chin J Cancer · Pubmed #22958741.

ABSTRACT: For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6%, respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significant longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.

23 Article GLP-1 and glucagon secretion from a pancreatic neuroendocrine tumor causing diabetes and hyperinsulinemic hypoglycemia. 2012

Roberts, Rachel E / Zhao, Min / Whitelaw, Ben C / Ramage, John / Diaz-Cano, Salvador / le Roux, Carel W / Quaglia, Alberto / Huang, Guo Cai / Aylwin, Simon J B. ·King's College London School of Medicine, London SE1 1UL, United Kingdom. ·J Clin Endocrinol Metab · Pubmed #22774207.

ABSTRACT: CONTEXT: Glucagon-like peptide-1 (GLP-1) is a gut peptide that promotes insulin release from pancreatic β-cells and stimulates β-cell hyperplasia. GLP-1 secretion causing hypoglycemia has been described once from an ovarian neuroendocrine tumor (NET) but has not been reported from a pancreatic NET (pNET). OBJECTIVE: A 56-yr-old male with a previous diagnosis of diabetes presented with fasting hypoglycemia and was found to have a metastatic pNET secreting glucagon. Neither the primary tumor nor metastases stained for insulin, whereas the resected normal pancreas showed histological evidence of islet cell hyperplasia. We provide evidence that GLP-1 secretion from the tumor was the cause of hyperinsulinemic hypoglycemia. METHODS: GLP-1 levels were determined in the patient, and immunohistochemistry for GLP-1 was performed on the tumor metastases. Ex vivo tissue culture and a bioassay constructed by transplantation of tumor into nude mice were performed to examine the tumor secretory products and their effects on islet cell function. RESULTS: The patient had high levels of glucagon and GLP-1 with an exaggerated GLP-1 response to oral glucose. Immunohistochemistry and primary tissue culture demonstrated secretion of glucagon and GLP-1 from the tumor metastases, whereas insulin secretion was almost undetectable. Ex vivo coculture of the tumor with normal human islets resulted in inhibition of insulin release, and transplanted mice developed impaired glucose tolerance. CONCLUSIONS: This is the first description of glucagon and GLP-1 secretion from a metastatic pNET causing sequential diabetes and hypoglycemia. Hypoglycemia was caused by insulin secretion from hyperplastic β-cells stimulated by tumor-derived GLP-1.

24 Article Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells. 2012

Liu, Ling / Lin, Zhi-Xiu / Leung, Po Sing / Chen, Li-Hua / Zhao, Ming / Liang, Juan. ·School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, P.R. China. ·Int J Mol Med · Pubmed #22552257.

ABSTRACT: The fruit of Brucea javanica L. is a common herb used in Chinese medicine for the treatment of a variety of cancers. Our research group has previously identified bruceine D (BD), a quassinoid found abundantly in B. javanica, to have potent cytotoxic effect on a number of pancreatic cancer cell lines, including Panc-1, SW1990 and Capan-1 cells. In the present study, we showed that BD was also able to inhibit the growth of the Capan-2 human pancreatic adenocarcinoma cell line, but it exerted only modest cytotoxicity on the WRL68 human hepatocyte cell line and a human pancreatic progenitor cell line. The antiproliferative effects of BD were comparable to those exhibited by camptothecin and gemcitabine in our culture system. We found a dose-dependent decrease of the mitochondrial membrane potential in BD-treated Capan-2 cells as measured by the JC-1 assay. BD exposure was able to attenuate the expression of Bcl-2 protein in Capan-2 cells as detected by western blot analysis. In addition, the expression of both caspase 9 and caspase 3 in BD-treated Capan-2 cells was significantly accentuated. Moreover, BD was capable of inducing the fragmentation of genomic DNA in Capan-2 cells as evidenced by Hoechst staining. Cell cycle analysis demonstrated that BD could increase the percentage of Capan-2 cells in the subG1 phase in a dose-related manner. An increase in the apoptosis of Capan-2 cells was also observed by Annexin V and PI staining. These results unequivocally indicate that BD induces cytotoxicity in Capan-2 cells via the induction of cellular apoptosis involving the mitochondrial pathway.

25 Article A polymeric nanoparticle encapsulated small-molecule inhibitor of Hedgehog signaling (NanoHHI) bypasses secondary mutational resistance to Smoothened antagonists. 2012

Chenna, Venugopal / Hu, Chaoxin / Pramanik, Dipankar / Aftab, Blake T / Karikari, Collins / Campbell, Nathaniel R / Hong, Seung-Mo / Zhao, Ming / Rudek, Michelle A / Khan, Saeed R / Rudin, Charles M / Maitra, Anirban. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ·Mol Cancer Ther · Pubmed #22027695.

ABSTRACT: Aberrant activation of the hedgehog (Hh) signaling pathway is one of the most prevalent abnormalities in human cancer. Tumors with cell autonomous Hh activation (e.g., medulloblastomas) can acquire secondary mutations at the Smoothened (Smo) antagonist binding pocket, which render them refractory to conventional Hh inhibitors. A class of Hh pathway inhibitors (HPI) has been identified that block signaling downstream of Smo; one of these compounds, HPI-1, is a potent antagonist of the Hh transcription factor Gli1 and functions independent of upstream components in the pathway. Systemic administration of HPI-1 is challenging due to its minimal aqueous solubility and poor bioavailability. We engineered a polymeric nanoparticle from [poly(lactic-co-glycolic acid); (PLGA)] conjugated with polyethylene glycol (PEG), encapsulating HPI-1 (NanoHHI). NanoHHI particles have an average diameter of approximately 60 nm, forms uniform aqueous suspension, and improved systemic bioavailability compared with the parent compound. In contrast to the prototype targeted Smo antagonist, HhAntag (Genentech), NanoHHI markedly inhibits the growth of allografts derived from Ptch(-/+); Trp53(-/-) mouse medulloblastomas that harbor a Smo(D477G) binding site mutation (P < 0.001), which is accompanied by significant downregulation of mGli1 as well as bona fide Hh target genes (Akna, Cltb, and Olig2). Notably, NanoHHI combined with gemcitabine also significantly impedes the growth of orthotopic Pa03C pancreatic cancer xenografts that have a ligand-dependent, paracrine mechanism of Hh activation when compared with gemcitabine alone. No demonstrable hematologic or biochemical abnormalities were observed with NanoHHI administration. NanoHHI should be amenable to clinical translation in settings where tumors acquire mutational resistance to current Smo antagonists.

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