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Biomedical subjects

M M Fraser

Publications and source records attributed to M M Fraser.

5 recordsLinked to original sources
PubMed2001

CaSm/gemcitabine chemo-gene therapy leads to prolonged survival in a murine model of pancreatic cancer.

BACKGROUND: CaSm, the cancer-associated Sm-like oncogene, is overexpressed in greater than 80% of pancreatic tumors. We previously reported that an adenovirus expressing antisense RNA to CaSm (Ad-alpha CaSm) can decrease pancreatic tumor growth in vivo but is not curative. In the current study we investigated the mechanism of Ad-alpha CaSm's antitumor effect to rationally approach combinatorial therapy for improved efficacy. METHODS: AsPC-1 and Panc-1 human pancreatic cancer cells were treated with Ad-alpha CaSm and examined by MTT assay for in vitro proliferation changes. Flow cytometry determined the effect of CaSm down-regulation on the cell cycle, and then cells treated with Ad-alpha CaSm in combination with cisplatin, etoposide, or gemcitabine chemotherapies were reexamined by MTT assay. SCID-Bg mice bearing subcutaneous AsPC-1 tumors were treated with Ad-alpha CaSm, gemcitabine, or the combination and monitored for tumor growth and survival. RESULTS: Treatment with Ad-alpha CaSm reduced the proliferation of AsPC-1 and Panc-1 cells (59% and 44%, respectively; P <.05). The cell cycle revealed a cytostatic block with decreased G(1) phase and increased DNA content in treated cells. The combination of Ad-alpha CaSm with gemcitabine significantly reduced in vitro proliferation (66% vs 39% and 48% for controls), decreased in vivo AsPC-1 tumor growth by 71% (n = 10), and extended survival time from 57 to 100 days. CONCLUSIONS: Down-regulation of CaSm reduces the growth of pancreatic cancer cells by altering the cell cycle in a cytostatic manner. The combination of Ad-alpha CaSm with gemcitabine is more effective than either agent used separately.

Animals↗
PubMed1979

Endodermal sinus (yolk sac) tumors in infants and children.

Endodermal sinus tumors, as a specific entity, were first proposed and described by Teilum on the basis of morphological and histogenetic features. Recent work utilizing tumor markers (alpha-fetoprotein), immunofluorescent and electron microscopic studies have supported Teilum's original concept as to the origin of these tumors. Five typical presentations of endodermal sinus tumors seen in the pediatric age group were reviewed with reference to the original presentation, the utilization of tumor markers (alpha-fetoprotein) and the prognostic implications of this neoplasm.

Child↗
PubMedDate not supplied

Cost efficacy of routine screening for diabetes in pregnancy: 1-h versus 2-h specimen.

Undetected gestational diabetes mellitus (GDM) is associated with a two- to fivefold increase in perinatal morbidity and mortality. Widespread screening of the obstetric population (resulting in identification and treatment) should reduce these rates. Seven hundred ninety-eight women were examined during a 13-mo period of universal glucose challenge testing (GCT). A total of 2.8% of the population had an abnormal oral glucose tolerance test (OGTT). Thirty percent of those with an abnormal OGTT were less than 25 yr old. The specificity of a 1-h GCT (50-g carbohydrate load) using a threshold of either 140 or 150 mg/dl was compared with that of a 2-h specimen using a threshold of 118 mg/dl to determine whether the cost of screening could be reduced. One- and 2-h specimens were obtained in 347 of these women. A 34% reduction in the number of follow-up OGTTs required would have been achieved if a 2-h specimen had been used as the index instead of a 1-h specimen (P less than .05). As a result, the (direct and indirect) cost per patient identified with GDM would have declined 23.5%--from $866 to $662. No comment concerning the actual false-negative rate of either the 1- or 2-h GCT can be made because only select women underwent an OGTT. To assess the validity of the 2-h threshold, an OGTT was performed in an additional 190 women if either the 1- or 2-h screen was abnormal. The results were confirmatory: the 2-h screen would have reduced the cost per case identified by 32% in this small group. Screening on the basis of past medical history clearly lacked sensitivity and cost efficacy in comparison with the GCT and should be abandoned as a practice.

Adolescent↗