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Pancreatic Neoplasms: HELP
Articles by James Helm
Based on 8 articles published since 2009
(Why 8 articles?)

Between 2009 and 2019, James Helm wrote the following 8 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Editorial MicroRNAs in pancreatic ductal adenocarcinoma. 2011

Park, Jong Y / Helm, James / Coppola, Domenico / Kim, Donghwa / Malafa, Mokenge / Kim, Seung Joon. · ·World J Gastroenterol · Pubmed #21412491.

ABSTRACT: Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, biomarkers for early detection and new therapeutic strategies are urgently needed. miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the post-transcriptional level. miRNAs regulate proteins involved in critical cellular processes such as differentiation, proliferation, and apoptosis. Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites, including the pancreas. Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes, as well as play a role in other mechanisms of carcinogenesis. The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.

2 Article SLC5A8 nuclear translocation and loss of expression are associated with poor outcome in pancreatic ductal adenocarcinoma. 2012

Helm, James / Coppola, Domenico / Ganapathy, Vadivel / Lloyd, Mark / Centeno, Barbara A / Chen, Dung-Tsa / Malafa, Mokenge P / Park, Jong Y. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. ·Pancreas · Pubmed #22450368.

ABSTRACT: OBJECTIVES: This study aimed to assess the role of SLC5A8 expression in the survival of pancreatic cancer. METHODS: We determined SLC5A8 expression in pancreatic ductal adenocarcinoma and adjacent non-neoplastic pancreas (NNP) obtained from 110 patients who underwent pancreatectomy. Formalin-fixed paraffin-embedded core sections in a tissue microarray were immunostained using polyclonal anti-SLC5A8 antibody, and a semiquantitative measure of SLC5A8 expression was determined. RESULTS: SLC5A8 expression was low in 56% (62/110) of pancreatic cancers as compared to NNP that had low expression in only 9% (10/107) of specimens (P < 0.0001). All cells expressing SLC5A8 did so in the cytoplasm, whether they are neoplastic or not. Nuclear expression of SLC5A8 occurred in 38% (42/110) of cancers, but it was uncommon in NNP (7%, 8/107) (P < 0.0001). Kaplan-Meier estimates showed that survival in patients whose cancers had low SLC5A8 expression, and/or nuclear expression, was significantly worse than in patients whose cancers had none of these abnormalities (P = 0.02). For the 88 patients whose cancers had abnormal SLC5A8 expression, median survival was 1.4 years, as compared to 3.9 years in patients whose cancers both expressed high levels of SLC5A8 and lacked nuclear expression. CONCLUSIONS: SLC5A8 nuclear translocation and loss of expression are associated with poor outcome in pancreatic ductal adenocarcinoma.

3 Article Palladin is a marker of liver metastasis in primary pancreatic endocrine carcinomas. 2011

Henderson-Jackson, Evita B / Helm, James / Strosberg, Jonathan / Nasir, Nelly A / Yeatman, Timothy J / Kvols, Larry K / Coppola, Domenico / Nasir, Aejaz. ·Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. ·Anticancer Res · Pubmed #21868544.

ABSTRACT: BACKGROUND: Palladin is a metastasis-associated gene regulating cell motility. The expression of palladin protein in pancreatic neuroendocrine tumors (PET) and carcinomas (PECA) is not known. MATERIALS AND METHODS: A tissue microarray (TMA) of well-differentiated (WD) PETs/PECAs (AJCC 2010) and non-neoplastic, histologically normal pancreatic tissue/islets (HNPIs) was immunostained with palladin antibody and quantified using the Allred score. The results were correlated with the presence or absence of liver metastases. RESULTS: The retrospective study included 19 males and 19 females of age 27-79 years (mean 54). Tumor size was 0.9-11.5 cm (mean 3.8). Palladin expression was cytoplasmic and/or membranous. The tumors with high palladin expression were associated with liver metastasis (p<0.0001). All 14 primary PECA with hepatic metastases (MP-PECAs) exhibited palladin expression whereas 14 out of 24 (58%) clinically-localized primary PET (CLP-PETs) expressed palladin (p<0.01) with median Allred scores of 5 (range 3-7) and 2 (range 0-6) respectively (p<0.0001). The mean Allred score for the HNPIs in the MP-PECAs (N=6) was higher (4.2) as compared to that in the CLP-PETs (2.5,N=11) (p=0.23). CONCLUSION: Palladin may identify primary pancreatic endocrine neoplasms with a propensity to metastasize to the liver.

4 Article Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. 2011

Patel, Manish / Hoffe, Sarah / Malafa, Mokenge / Hodul, Pamela / Klapman, Jason / Centeno, Barbara / Kim, Jongphil / Helm, James / Valone, Tiffany / Springett, Gregory. ·Division of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. ·J Surg Oncol · Pubmed #21520097.

ABSTRACT: BACKGROUND AND OBJECTIVES: To improve the likelihood of achieving a margin-free resection, neoadjuvant induction chemotherapy with GTX (gemcitabine, docetaxel, and capecitabine) followed by 5-FU-IMRT was administered to patients with borderline resectable pancreatic cancer. The utility of computed tomography (CT), endoscopic ultrasound (EUS), positron emission tomography (PET), and CA 19-9 during diagnostic workup and assessment of response was also examined. METHODS: Seventeen patients with borderline resectable pancreatic cancer received a median of three cycles of neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT with dose painting. CA 19-9, CT mass size, and PET SUV were examined before and after neoadjuvant treatment. RESULTS: Diagnostic EUS and CT scans displayed similar mean mass sizes and extent of vascular involvement. Eight of the 17 patients achieved an R0 resection. Median CA 19-9 levels, CT mass size, and PET SUV all significantly decreased after neoadjuvant therapy. The median progression-free survival and overall survival were 10.48 and 15.64 months, respectively. Six patients are still alive. CONCLUSIONS: Neoadjuvant GTX induction chemotherapy followed by 5-FU-IMRT shows promise in improving the likelihood of resectability with negative margins in borderline resectable pancreatic cancer. CT and EUS play complimentary roles during diagnostic workup. CT scans, CA 19-9, and PET scans are useful in judging response to neoadjuvant therapy.

5 Article RUNX1T1: a novel predictor of liver metastasis in primary pancreatic endocrine neoplasms. 2011

Nasir, Aejaz / Helm, James / Turner, Leslie / Chen, Dung-Tsa / Strosberg, Jonathan / Hafez, Naiel / Henderson-Jackson, Evita B / Hodul, Pamela / Bui, Marilyn M / Nasir, Nelly A / Hakam, Ardeshir / Malafa, Mokenge P / Yeatman, Timothy J / Coppola, Domenico / Kvols, Larry K. ·Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. nasir_aejaz@lilly.com ·Pancreas · Pubmed #21499216.

ABSTRACT: OBJECTIVES: Using gene expression profiling on frozen primary pancreatic endocrine tumors (PETs), we discovered RUNX1T1 as a leading candidate progression gene. This study was designed (1) to validate the differential expression of RUNX1T1 protein on independent test sets of metastatic and nonmetastatic PETs and (2) to determine if RUNX1T1 underexpression in primary tumors was predictive of liver metastases. METHODS: Immunohistochemical expression of RUNX1T1 protein was quantified using Allred scores on archival metastatic (n = 13) and nonmetastatic (n = 24) primary adult PET tissues using custom-designed tissue microarrays. Wilcoxon rank sum/Fisher exact tests and receiver operating characteristic curves were used in the data analysis. RESULTS: Median RUNX1T1 scores were 2 (2-7) and 6 (3-8) in metastatic versus nonmetastatic primaries (P < 0.0001). Eleven of 13 metastatic and 1 of 24 nonmetastatic primaries exhibited RUNX1T1-scores of 4 or less (P < 0.0001). Low RUNX1T1 expression was highly associated with hepatic metastases (P < 0.0001), whereas conventional histological criteria (Ki-67 index, mitotic rate, necrosis) were weakly associated with metastases (P = 0.08-0.15). Considering RUNX1T1 expression (Allred) score of 4 or less to be predictive, the sensitivity to predict hepatic metastases was 85%, with a specificity of 96%. CONCLUSIONS: RUNX1T1 protein is underexpressed in well-differentiated metastatic primary PETs relative to nonmetastatic primaries and emerges as a promising novel biomarker for prediction of liver metastases.

6 Article Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. 2011

Coppola, Domenico / Helm, James / Ghayouri, Msoumeh / Malafa, Mokenge P / Wang, Hong-Gang. ·Department of Anatomic Pathology, University of South Florida, Tampa, FL, USA. Domenico.Coppola@moffitt.org ·Pancreas · Pubmed #21283040.

ABSTRACT: OBJECTIVE: Bax-interacting factor 1 (Bif-1) protein plays a critical role in apoptosis, mitochondrial morphogenesis, and autophagy, and its loss promotes tumorigenesis. The role of Bif-1 in pancreatic cancer has not been studied. METHODS: We determined Bif-1 expression in 82 human pancreatic ductal adenocarcinomas (PDCs) and in 82 nonmalignant pancreatic specimens (NMPs), using immunohistochemistry and tissue microarray. Bif-1 immunostain was semiquantitatively scored on a scale of 0 to 9. RESULTS: Bif-1 scores in NMP were either 6 or 9, with lower scores in only 19 (23.2%) of 82 NMPs. Low Bif-1 expression (score <6) was found in 37 (45.1%) of 82 PDCs, a proportion significantly greater than that found in NMP (P = 0.005). The expression of Bif-1 was twice as likely to be low in PDC as in NMP (relative risk = 1.95, 95% confidence interval, 1.23-3.09). Kaplan-Meier survival estimates showed no difference in survival between patients with low and high Bif-1 expression (P = 0.21, log-rank test). CONCLUSIONS: The expression of Bif-1 is downregulated in a subset of PDC. This novel finding is in agreement with the tumor suppressor function of Bif-1. The lack of association between Bif-1 expression and patient survival may be best explained by the complexity of carcinogenesis.

7 Article First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. 2011

Strosberg, Jonathan R / Fine, Robert L / Choi, Junsung / Nasir, Aejaz / Coppola, Domenico / Chen, Dung-Tsa / Helm, James / Kvols, Larry. ·Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. jonathan.strosberg@moffitt.org ·Cancer · Pubmed #20824724.

ABSTRACT: BACKGROUND: Temozolomide is an active agent in metastatic pancreatic endocrine carcinomas. In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The authors retrospectively evaluated the efficacy of capecitabine and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas to assess response rate, progression free survival (PFS), and overall survival (OS). METHODS: Patients with metastatic, well, or moderately differentiated pancreatic endocrine carcinomas who had not received prior systemic chemotherapy were treated with capecitabine (750 mg/m² twice daily, days 1-14) and temozolomide (200 mg/m² once daily, days 10-14) every 28 days. RESULTS: Among 30 patients treated, 21 (70%) patients achieved an objective radiographic response. Median progression-free survival was 18 months. The rate of survival at two years was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events. CONCLUSIONS: The combination of capecitabine and temozolomide is associated with an exceptionally high and durable response rate in metastatic endocrine carcinomas of the pancreas. Clinical endpoints, including response rate, survival, and toxicity, are superior to those observed with streptozocin-based regimens.

8 Article Histologic characteristics enhance predictive value of American Joint Committee on Cancer staging in resectable pancreas cancer. 2009

Helm, James / Centeno, Barbara A / Coppola, Domenico / Melis, Marcovalerio / Lloyd, Mark / Park, Jong Y / Chen, Dung-Tsa / Malafa, Mokenge P. ·Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida, USA. james.helm@moffitt.org ·Cancer · Pubmed #19626671.

ABSTRACT: BACKGROUND: American Joint Committee on Cancer (AJCC) anatomic stage group is considered relatively nondiscriminatory for predicting differences in survival after pancreatectomy for ductal adenocarcinoma, a perception confirmed in the authors' patients and by other reports. The authors' aim was to investigate the potential for improving the predictive value of AJCC staging by incorporating individually predictive histologic features into AJCC tumor-node-metastasis classification of anatomic extent, and determine the simplest combination of tumor characteristics predicting survival. METHODS: The authors determined survival of 137 patients who underwent pancreatectomy for ductal adenocarcinoma with curative intent (stage Groups IA-IIB) at Moffitt Cancer Center during the last 2 decades using data obtained from medical record review, the Moffitt Cancer Registry, and the Social Security Death Index. Histologic characteristics were confirmed by expert review. RESULTS: Median survival was 21.2 months after pancreatectomy with a 3-year disease-specific survival of 36%. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard modeling found worse survival with local extrapancreatic extension, poorly differentiated histology, and lymphatic invasion within tumor (P<.05). Survival was not worse with nodal metastases, microscopically positive resection margins, and perineural or venous invasion, nor was survival better with cancer arising from an intraductal papillary mucinous neoplasm. Kaplan-Meier estimates for different variable combinations showed prognosis was best for well- or moderately differentiated tumors without lymphatic invasion and confined to the pancreas (9.9 years median survival), worst for poorly differentiated tumors with lymphatic invasion and local extension beyond the pancreas (8.5 months median survival), and intermediate for well- or moderately differentiated tumors with either lymphatic invasion or local extension beyond the pancreas (21.2 months median survival). CONCLUSIONS: A simple combination of tumor differentiation, lymphatic invasion within the tumor, and local extrapancreatic extension predicts survival after pancreatectomy for ductal adenocarcinoma.