Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by David Z. Chang
Based on 11 articles published since 2009
(Why 11 articles?)
||||

Between 2009 and 2019, D. Z. Chang wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients. 2017

Laquente, Berta / Lopez-Martin, Jose / Richards, Donald / Illerhaus, Gerald / Chang, David Z / Kim, George / Stella, Philip / Richel, Dirk / Szcylik, Cezary / Cascinu, Stefano / Frassineti, G L / Ciuleanu, Tudor / Hurt, Karla / Hynes, Scott / Lin, Ji / Lin, Aimee Bence / Von Hoff, Daniel / Calvo, Emiliano. ·Institut Català d'Oncologia-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), Barcelona, Spain. · University Hospital and Research Institute, Madrid, Spain. · US Oncology Research, Tyler, USA. · Hematology, Onkology, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany. · Virginia Oncology Associates, Eastern Virginia Medical School, US Oncology Research, Hampton, VA, USA. · 21st Century Oncology, University of Florida Health Oncology, Jacksonville, USA. · St. Joseph Mercy Hospital, Ypsilanti, MI, USA. · Academic Medical Center, Amsterdam, Netherlands. · Department of Oncology, Military Institute of Medicine, Warsaw, Poland. · Department of Oncology and Hematology, Universitá di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy. · Department of Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. · Institute of Oncology Ion Chiricuta, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca, Romania. · Eli Lilly and Company, Indianapolis, IN, USA. · Translational Genomics Research Institute (TGen) and HonorHealth Research Institute, Phoenix, AZ, USA. · START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Medical Oncology Division, Hospital Universitario Madrid Norte Sanchinarro, Calle Oña, 10, 28050, Madrid, Spain. emiliano.calvo@start.stoh.com. ·BMC Cancer · Pubmed #28202004.

ABSTRACT: BACKGROUND: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. METHODS: Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2:1) to either 230 mg of LY2603618/1000 mg/m RESULTS: Ninety-nine patients (n = 65, LY2603618/gemcitabine; n = 34, gemcitabine) were randomized (intent-to-treat population). The median OS (months) was 7.8 (range, 0.3-18.9) with LY2603618/gemcitabine and 8.3 (range, 0.8-19.1+) with gemcitabine. Similarly, in a Bayesian analysis, the study was not positive since the posterior probability that LY2603618/gemcitabine was superior to gemcitabine in improving OS was 0.3, which did not exceed the prespecified threshold of 0.8. No significant improvements in PFS, ORR, or duration of response were observed. Drug-related treatment-emergent AEs in both arms included nausea, thrombocytopenia, fatigue, and neutropenia. The severity of AEs with LY2603618/gemcitabine was comparable to gemcitabine. The LY2603618 exposure targets (AUC CONCLUSIONS: LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. TRIAL REGISTRATION: NCT00839332 . Clinicaltrials.gov. Date of registration: 6 February 2009.

2 Clinical Trial Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas. 2012

Meng, Z / Garrett, C R / Shen, Y / Liu, L / Yang, P / Huo, Y / Zhao, Q / Spelman, A R / Ng, C S / Chang, D Z / Cohen, L. ·Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. ·Br J Cancer · Pubmed #22782343.

ABSTRACT: BACKGROUND: An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas. METHODS: Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m(-2) on days 1, 8, and 15 with huachansu 20 ml m(-2) daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity. RESULTS: A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679). CONCLUSION: Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.

3 Clinical Trial Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. 2009

Meng, Zhiqiang / Yang, Peiying / Shen, Yehua / Bei, Wenying / Zhang, Ying / Ge, Yongqian / Newman, Robert A / Cohen, Lorenzo / Liu, Luming / Thornton, Bob / Chang, David Z / Liao, Zongxing / Kurzrock, Razelle. ·International Center of Integrative Oncology, Fudan University Cancer Hospital, Shanghai, China. ·Cancer · Pubmed #19701908.

ABSTRACT: BACKGROUND: Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo gargarizans or B. melanostictus, has been used in the treatment of various cancers in China. The authors conducted a pilot study, using a phase 1 trial design, of huachansu in patients with advanced cancer. METHODS: Huachansu was administered intravenously for 14 days followed by 7 days off (1 cycle). Without significant adverse events or progressive disease, treatment continued beyond 2 cycles. The dose of huachansu was escalated as follows with 3 patients per cohort: 10 (level 1), 20 (level 2), 40 (level 3), 60 (level 4), and 90 (level 5) mL/m(2). RESULTS: Fifteen patients (hepatocellular cancer, n = 11; nonsmall cell lung cancer, n = 2; pancreatic cancer, n = 2) were enrolled in the trial, and no dose-limiting toxicities (DLTs) were found. Eleven patients had no drug-related toxicity greater than grade 1. Six (40%) had stable disease (median duration, 6.0 months; range, 3.5-11.1 months). One of these patients (with hepatocellular cancer) had 20% regression (duration, 11 months) (dose level 1). Quality of life improved for patients with stable disease. Plasma bufalin concentration reached maximal levels at the end of the 2-hour infusion and was proportional to the amount of drug being administered (0.81-3.38 ng/mL). CONCLUSIONS: No DLT was observed with the use of huachansu at doses up to 8x higher than typically used in China. Six patients had prolonged stable disease or minor tumor shrinkage.

4 Article Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral 2017

Li, Ming / Radvanyi, Laszlo / Yin, Bingnan / Li, Jia / Chivukula, Raghavender / Lin, Kevin / Lu, Yue / Shen, JianJun / Chang, David Z / Li, Donghui / Johanning, Gary L / Wang-Johanning, Feng. ·Viral Oncology Program, Center for Cancer and Metabolism, SRI International, Menlo Park, California. · EMD Serono Research and Development Institute, Billerica, Massachusetts. · Department of Inflammation and Epigenetics, Methodist Research Institute, Houston, Texas. · Department of Epigenetics and Molecular Carcinogenesis, Science Park, the University of Texas MD Anderson Cancer Center, Smithville, Texas. · Virginia Oncology Associates, Newport News, Virginia. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Viral Oncology Program, Center for Cancer and Metabolism, SRI International, Menlo Park, California. feng.wang-johanning@sri.com. ·Clin Cancer Res · Pubmed #28679769.

ABSTRACT:

5 Article Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. 2012

Chang, David Z / Ma, Ying / Ji, Baoan / Liu, Yan / Hwu, Patrick / Abbruzzese, James L / Logsdon, Craig / Wang, Huamin. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. David.Chang@USOncology.com ·J Hematol Oncol · Pubmed #22475564.

ABSTRACT: PURPOSE: Cell division cycle 20 (CDC20) homolog is an anaphase-promoting complex activator that is essential for cell division, but whether its expression in pancreatic ductal adenocarcinoma (PDAC) is significant is unknown. In this retrospective study, we determined whether aberrant CDC20 expression can be used as a biomarker in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and whether its expression reflects clinical progression. EXPERIMENTAL DESIGN: We compared CDC20 expression levels in normal, cancerous, and inflamed pancreatic tissues from stage II PDAC patients with clinical outcomes and determined CDC20 levels in seven PDAC cell lines. CDC20 was identified using a cDNA microarray database containing gene expression profiles for PDAC tissues and cell lines and chronic pancreatitis and normal pancreas tissues. Its expression was confirmed by real-time quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR). An immunohistochemical analysis of tissue microarrays from resected PDAC tumors and paired benign pancreatic tissues was done and CDC20 levels were correlated with clinical outcome. RESULTS: Fifty-six patients were included in this study. A microarray analysis revealed 5-fold higher CDC20 expression in PDAC tissue than in chronic pancreatitis tissue. A qRT-PCR analysis confirmed a mean 20-fold higher CDC20 level in PDAC tissue than in normal pancreas and pancreatitis tissue. RNA and protein CDC20 expression was detected in several PDAC cell lines. An immunohistochemical analysis revealed higher CDC20 protein expression levels in PDAC tissue than in normal pancreas tissue, and high CDC20 expression was associated with poor differentiation (P = 0.020) and a significantly lower 5-year recurrence-free survival rate (P = 0.039); we also found a trend toward a shorter overall survival duration. CONCLUSIONS: Aberrant CDC20 expression may play an important role in PDAC tumorigenesis and progression and may thus be useful as a marker of disease progression and prognosis and as a therapeutic target.

6 Article Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. 2011

Chang, David Z / Ma, Ying / Ji, Baoan / Wang, Huamin / Deng, Defeng / Liu, Yan / Abbruzzese, James L / Liu, Yong-jun / Logsdon, Craig D / Hwu, Patrick. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. David.Chang@USOncology.com ·Clin Cancer Res · Pubmed #21976550.

ABSTRACT: PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. EXPERIMENTAL DESIGN: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras(G12V)). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit(w-sh/w-sh) mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. RESULTS: In the spontaneous mouse model of PDAC (K-ras(G12V)), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit(w-sh/w-sh) mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. CONCLUSIONS: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.

7 Article Combining betulinic acid and mithramycin a effectively suppresses pancreatic cancer by inhibiting proliferation, invasion, and angiogenesis. 2011

Gao, Yong / Jia, Zhiliang / Kong, Xiangyu / Li, Qiang / Chang, David Z / Wei, Daoyan / Le, Xiangdong / Suyun, Huang / Huang, Shengdong / Wang, Liwei / Xie, Keping. ·Department of Oncology, Shanghai Tongji University Affiliated East Hospital, Shanghai. ·Cancer Res · Pubmed #21673052.

ABSTRACT: Both betulinic acid (BA) and mithramycin A (MIT) exhibit potent antitumor activity through distinct mechanisms of Sp1 inhibition. However, it is unknown whether a combination of these two compounds results in a synergistic inhibitory effect on pancreatic cancer growth and/or has a therapeutic advantage over gemcitabine. In xenograft mouse models of human pancreatic cancer, treatment with either BA or MIT alone showed dose-dependent antitumor activity but led to systemic side effects as measured by overall weight loss. Treatment with a nontoxic dose of either compound alone had only marginal antitumor effects. Importantly, combination treatment with nontoxic doses of BA and MIT produced synergistic antitumor activity, including inhibitory effects on cell proliferation, invasion, and angiogenesis. The treatment combination also produced less discernible side effects than therapeutic doses of gemcitabine. Moreover, combined treatment of BA and MIT resulted in drastic inhibition of Sp1 recruitment onto Sp1 and VEGF promoters, leading to transcriptional inhibition of both Sp1 and VEGF and downregulation of Sp1 and VEGF protein expression. Ectopic overexpression of Sp1 rendered tumor cells resistant to BA, MIT, and the combination of the two. Overall, our findings argue that Sp1 is an important target of BA and MIT and that their combination can produce an enhanced therapeutic response in human pancreatic cancer.

8 Article Multimodality treatment of pancreatic cancer with liver metastases using chemotherapy, radiation therapy, and/or Chinese herbal medicine. 2011

Ouyang, Huaqiang / Wang, Peng / Meng, Zhiqiang / Chen, Zhen / Yu, Er'xin / Jin, Huan / Chang, David Z / Liao, Zhongxing / Cohen, Lorenzo / Liu, Luming. ·Department of Integrative Oncology, Cancer Hospital, and Department of Biostatistics and Social Medicine, School of Public Health, Fudan University, Shanghai, China. ·Pancreas · Pubmed #20683216.

ABSTRACT: OBJECTIVE: To explore the utility of multidisciplinary approaches in the treatment of patients with pancreatic cancer with liver metastases (PCLM). METHODS: From 2002 to 2007, a total of 164 consecutive patients with PCLM treated with chemotherapy, radiation therapy, and/or Chinese herbal medicine were included in this study. Clinical parameters, treatments received, and survival time from initial diagnosis were analyzed. RESULTS: Of the 164 patients, 113 (69%) were men and 51 (31%) were women, with median age of 58 years. One hundred thirty-two patients (80%) had synchronous liver metastases, and 57 patients (35%) had extrahepatic metastases. Overall median survival time of the 164 patients was 4.7 months; 23 (14%) were alive at least 12 months after initial diagnosis of liver metastases. Karnofsky performance status of less than 80, weight loss (>10% within 6 months), ascites, and carbohydrate antigen 19-9 of 1000 U/mL or greater were the most relevant predictors of poor survival. Multivariate analysis showed that chemotherapy and Chinese herbal medicine were protective factors. CONCLUSIONS: Multimodality treatment is well tolerated by patients with PCLM and may be effective in prolonging their survival. Awareness of the implications of these prognostic factors may assist in evaluating the survival potential of patients and selecting the most appropriate treatments.

9 Article Combined treatment of pancreatic cancer with mithramycin A and tolfenamic acid promotes Sp1 degradation and synergistic antitumor activity. 2010

Jia, Zhiliang / Gao, Yong / Wang, Liwei / Li, Qiang / Zhang, Jun / Le, Xiangdong / Wei, Daoyan / Yao, James C / Chang, David Z / Huang, Suyun / Xie, Keping. ·Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Cancer Res · Pubmed #20086170.

ABSTRACT: Mithramycin (MIT) and tolfenamic acid (TA) inhibit the activity of the transcription factor Sp1. In the present study, we investigated whether pancreatic cancer treatment with a combination of these compounds has a synergistic effect on Sp1 activity, tumor growth, and their underlying response mechanisms. Treatment of pancreatic tumor xenografts with MIT and TA produced dose-dependent antitumor activity, and significant antitumor activity of either compound alone was directly associated with systemic side effects. Combination treatment with nontoxic doses of both compounds produced synergistic antitumor activity, whereas treatment with a nontoxic dose of either compound alone lacked a discernible antitumor effect. Synergistic therapeutic effects correlated directly with synergistic antiproliferation and antiangiogenesis in vitro. Moreover, combination treatment resulted in Sp1 protein degradation, drastically downregulating expression of Sp1 and vascular endothelial growth factor. Our findings established that Sp1 is a critical target of TA and MIT in human pancreatic cancer therapy, rationalizing clinical studies to determine the effect of existing pancreatic cancer therapy regimens on Sp1 signaling in tumors and normal pancreatic tissue, and the ability of Sp1-targeting strategies to modify cancer responses.

10 Article Ras activity levels control the development of pancreatic diseases. 2009

Ji, Baoan / Tsou, Lilian / Wang, Huamin / Gaiser, Sebastian / Chang, David Z / Daniluk, Jaroslaw / Bi, Yan / Grote, Tobias / Longnecker, Daniel S / Logsdon, Craig D. ·Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Gastroenterology · Pubmed #19501586.

ABSTRACT: BACKGROUND & AIMS: Differentiated pancreatic acinar cells expressing endogenous levels of mutant K-Ras do not spontaneously develop pancreatic ductal adenocarcinoma (PDAC). However, we hypothesized that acinar cells would develop PDAC in the presence of Ras activity levels mimicking those of human tumor cells. METHODS: We measured Ras activity in PDAC cells from mice and humans using a Raf pull-down assay. We compared the effects of acinar cell expression of mutant K-Ras at endogenous and elevated levels on Ras activity and on the development of PDAC. RESULTS: Ras activity was greatly elevated in PDAC cells compared with nontransformed cells expressing endogenous levels of mutant K-Ras. Expression of endogenous levels of mutant K-Ras in differentiated acinar cells resulted in moderately elevated Ras activity and in sparse murine pancreatic intraepithelial neoplasias (mPanINs) that did not spontaneously advance to PDAC unless the tumor suppressor p53 was simultaneously deleted. In contrast, expression of mutant K-Ras at higher levels generated Ras activity equal to that in PDAC. High Ras activity mimicking levels in PDAC led to acinar cell senescence and generated inflammation and fibrosis resembling the histologic features of chronic pancreatitis. With higher Ras activity in acinar cells, abundant mPanINs formed and spontaneously progressed to both cystic papillary carcinoma and metastatic PDAC. CONCLUSIONS: There is an important relationship between Ras activity levels and the progression of PDAC. Sufficient Ras activity in pancreatic acinar induces several important pancreatic disease manifestations not previously reported and supports a potential direct linkage between chronic pancreatitis, cystic papillary carcinoma, and PDAC.

11 Article Synthetic microRNA targeting glioma-associated antigen-1 protein. 2009

Tsuda, Naotake / Mine, Takahi / Ioannides, Constantin G / Chang, David Z. ·Department of Gynecologic Oncology, Kurume University, Kurume, Japan. ·Methods Mol Biol · Pubmed #19301660.

ABSTRACT: The transcription factor glioma-associated antigen-1 (Gli-1) mediates activation of the sonic hedgehog (Shh) pathway, a process that precedes the transformation of tissue stem cells into cancerous stem cells and that is involved in early and late epithelial tumorigenesis. Hypothesizing that targeting the 3'-untranslated region (3'-UTR) of Gli-1 mRNA would effectively inhibit epithelial tumor cell proliferation, we evaluated several complementary miRNA molecules for their ability to do so. The synthetic miRNAs and corresponding duplex/small temporal RNAs were introduced as 3-nucleotide (nt) loops into GU-rich portions of the 3'UTR Gli-1 sequence. One particular miRNA (miRNA Gli-1-3548) and its corresponding duplex (Duplex 3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells by delaying cell division and activating late apoptosis in MiaPaCa-2 cells. Here, we describe the design of effective miRNA sequences and their applications as anti-gene agents.