Kristoffel R. Dumon

FHIT gene therapy prevents tumor development in Fhit-deficient mice

The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit+/− knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer.

Bariatric Surgery Outcomes

Obesity is associated with an increased risk of death, and morbid obesity carries a significant risk of life-threatening complications such as heart disease, diabetes, and high blood pressure. Bariatric surgery is recognized as the only effective treatment of morbid obesity. The estimated number of bariatric operations performed in the United States in 2008 was more than 13 times the number performed in 1992. Despite this increase, only 1% of the eligible morbidly obese population are currently treated with bariatric surgery.

Safety of a low-dosage Filgrastim (rhG-CSF) treatment in non-neutropenic surgical intensive care patients with an inflammatory process.

Objective:To evaluate the effect and safety of a low dose Filgrastim treatment in surgical intensive care patients.Design:Prospective, clinical study.Setting:Surgical intensive care unit (ICU) in a university hospital.Patients:Ten patients with the systemic inflammatory response syndrome (SIRS) and ten patients with sepsis were included in the study.Interventions:Filgrastim was given intravenously at 1.0 μg/kg for 3 days, followed by 0.5 μg/kg for 4 days.Measurements and results:Filgrastim treatment increased leukocyte counts and plasma levels of G-CSF. Cytokine levels (IL-6 and IL-8) decreased in the first 3 days of treatment. None of the SIRS patients developed sepsis or multiple organ failure and none of the patients died. In the sepsis group four patients died. No adverse side effects were observed, especially no attenuation of lung injury.Conclusions:Low-dosage Filgrastim treatment in ICU patients is safe. Whether the observed changes of the inflammatory response can be attributed to Filgrastim has to be clarified in further randomized trials.

What Is the Cost Associated with the Implementation and Maintenance of an ACS/APDS-Based Surgical Skills Curriculum?

PURPOSE The purpose of this study was to evaluate the cost associated with the American College of Surgery (ACS)/Association of Program Directors in Surgery (APDS)-based surgical skills curriculum (SSC) within a general surgery residency program. METHODS The Penn Surgical Simulation Center (PSSC) of the University of Pennsylvania was established by the Department of Surgery during the 2006-2007 academic year and became a Level-I ACS Accredited Education Institute in 2008. Each academic year, 38 junior residents are assigned to a 4-week dedicated simulation rotation based on the ACS/APDS-based SSC. In conjunction with voluntary participation by faculty, a salaried educational fellow is responsible for maintaining the schedule and administering the surgical skills training modules. The costs associated with the ACS/APDS-based SSC were divided in initial implementation capital expenses and annual operational maintenance expenses. RESULTS The overall capital expenditures associated with the implementation of the curriculum were

Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

4.204 million. These costs included the purchase of low and high-fidelity simulation equipment and initial construction costs to renovate a previous operating room (OR) and recovery suite into the Penn Medicine Clinical Simulation Center (PMCSC) which has housed the PSSC since 2008. The annual operational expenses are

Overexpression of Gsα subunit in thyroid tumors bearing a mutated Gsα gene

476,000 and include the salary for the educational fellow, disposables, and other supplies, and the PMCSC average student fees. The annual cost per resident for the 4-week dedicated simulation rotation is

Tumor suppressor functions of ARLTS1 in lung cancers

12,516. This figure does not include the average cost for teaching efforts including the simulation teaching per participating faculty member which is

Granulocyte colony-stimulating factor (G-CSF) serum levels in surgical intensive care patients

30,000 in Relative Teaching Value Units per year. CONCLUSIONS The expenditures associated with the implementation and maintenance of the ACS/APDS-based surgical skills curriculum in a surgical residency program are significant. This centers experience might be useful to programs deciding on more cost-effective means of implementing the ACS/APDS-SSC into their training.

The Surgical Management of Obesity

Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

Endoscopic treatments of obesity: a comprehensive review

Point mutations occurring at codon 201 of the gene coding for the α subunit of the stimulatory G protein impair intrinsic GTPase activity and lead to a constitutive activation of adenylate cyclase. We have examined thyroid follicular and papillary carcinomas and follicular adenomas and found samples that bear this mutation at codon 201 of the Gsα gene. Both mutation-positive and mutation-negative tissue samples were investigated for the level of Gsα expression relative to a pool of normal thyroid tissue, using immunoblotting against two (mid-region-specific and C-end-specific) antipeptide antibodies. Using 8000g and 100 000g membrane fractions of homogenized tissues we have demonstrated that the Gsα proteins in normal ad neoplastic thyroid tissues are represented by three isoforms: 43 kDa, 45 kDa and 52 kDa. We have quantified and compared the amount of Gsα protein and find it is overexpressed in mutation-bearing tissue samples.