Biomedical subjects

Dana A Osborne

Publications and source records attributed to Dana A Osborne.

4 recordsLinked to original sources

PubMed2006

Differential gene expression in patients genetically predisposed to pancreatic cancer.

BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. RESULTS: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

Adenocarcinoma↗

PubMed2006

EGF receptor antagonism improves survival in a murine model of pancreatic adenocarcinoma.

INTRODUCTION: The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer. METHODS: A human pancreatic cancer cell line (HPAC) was evaluated for the presence of EGFR with rtPCR and immunohistochemistry. Cells were grown in the presence of either 50 or 100 microM of erlotinib (EGFRI) for 72 hours and evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Eighty-six athymic nude/nude mice underwent orthotopic implantation of 10(7) HPAC cells and were blindly randomized into four groups: (1) Control; (2) Batimastat, a matrix metalloproteinase inhibitor (MMPI) at 400 ng/ml qod; (3) EGFRI at 100 mg/kg qd; and (4) MMPI and EGRRI (both). In vitro and in vivo effects of EGFRI with and without MMPI were compared. RESULTS: HPAC demonstrated high levels of expression of both the EGFR gene and the gene product. In vitro, both doses of EGFRI significantly reduced proliferation of HPAC at 48 (50 microM: 1.15 + 0.05 [st dev] versus 0.63 + 0.09 abs, P < 0.001) and 72 h (50 microM: 1.48 +/- 0.09 versus 0.73 +/- 0.05 abs, P < 0.001, paired Student's t-test). In vivo, each treatment group demonstrated a significant survival advantage (P = 0.0002 group 2, P = 0.0001 group 3, P = 0.012 group 4, log rank test) over controls. Mice treated with EGFRI showed reduced tumor implantation, size, weight, metastatic potential, and jaundice as compared to controls and MMPI-treated mice (all P < 0.05, Fisher's exact test). CONCLUSION: EGF receptor antagonism is not only a plausible therapy for treatment of ductal adenocarcinoma of the pancreas, but is also superior to matrix metalloproteinase inhibition alone or in combination.

Adenocarcinoma↗

PubMed2006

Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors.

BACKGROUND: Few data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors. METHODS: A prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival. RESULTS: A total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7+/-.70 (embolization) versus .8+/-.72 (cytoreduction; P=.27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22+/-13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P=.08 vs. embolization). The mean duration of relief was 35+/-22.0 months (P<.001 vs. embolization). The mean survival for the patients who underwent embolization was 24+/-15.8 months versus 43+/-26.1 months for those who underwent cytoreduction (P<.001). Survival in patients who underwent palliative cytoreduction was 32+/-18.9 months (P<.001 vs. embolization), whereas it was 50+/-27.6 months in patients who underwent curative resection (P<.001 vs. embolization; P<.001 vs. palliative). CONCLUSIONS: Cytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Carcinoid Tumor↗

PubMed2006

Laparoscopic cholecystectomy: past, present, and future.

Laparoscopic cholecystectomy is one of the most commonly undertaken procedures in General Surgery with more than 500,000 performed annually. Overall, the complication rate is less than 1.5%, and the mortality rate is less than 0.1%. As such, laparoscopic cholecystectomy was considered by most to be at its zenith since its inception in the early 1990 s. Advancements in technology and equipment have opened new doors to physicians and allowed the laparoscopic cholecystectomy to once again evolve. Traditional four-port cholecystectomy has given way to three- and even two-port techniques. Standard 12-mm ports have been replaced by 2-mm ports, and experiments have now been implemented to achieve cholecystectomy with no ports-known as the transgastric technique. The authors reviewed evolution of these techniques that included a synopsis of our experience with the three-port cholecystectomy, as well as the future direction of laparoscopic surgery.

Cholecystectomy, Laparoscopic↗