Biomedical subjects

Russell G Postier

Publications and source records attributed to Russell G Postier.

10 recordsLinked to original sources

PubMed2007

Expression profiling identifies microRNA signature in pancreatic cancer.

microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical clustering was able to distinguish tumor from normal pancreas, pancreatitis and cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including microRNAs previously reported as differentially expressed in other human cancers (miR-155, miR-21, miR-221 and miR-222) as well as those not previously reported in cancer (miR-376a and miR-301). Most of the top aberrantly expressed miRNAs displayed increased expression in the tumor. Expression of the active, mature microRNA was validated using a real-time PCR assay to quantify the mature microRNA and Northern blotting. Reverse transcription in situ PCR showed that three of the top differentially expressed miRNAs (miR-221, -376a and -301) were localized to tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA expression may offer new clues to pancreatic tumorigenesis and may provide diagnostic biomarkers for pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed2006

Tigecycline for the treatment of infections due to resistant Gram-positive organisms.

Tigecycline is a novel compound in the antimicrobial class known as the glycylcyclines. In vitro studies have shown it to have activity against the vast majority of Gram-positive pathogens, including multi-drug resistant Staphylococcus aureus and vancomycin-resistant enterococci. Tigecycline has also shown excellent in vitro activity against a broad range of Gram-negative enteric organisms including strains resistant to other antimicrobials as well as anaerobes. Tigecycline is not affected by the ribosomal protection and efflux mechanisms transmitted by the known tetracycline resistance genes. Tigecycline represents an exciting new class of glycylcycline antimicrobial agents for the treatment of multi-drug resistant Gram-positive bacteria. Although its broad spectrum of activity, which also includes Gram-negative enterics, makes it a candidate for empiric therapy for intra-abdominal infections, its spectrum against multi-drug resistant Gram-positive organisms makes it a very attractive choice for empiric treatment of Gram-positive infections in patients at risk for resistant strains. The two pivotal Phase II clinical trials involving complicated skin and soft tissue infections and intra-abdominal infections have shown the drug to be safe and effective.

Animals↗

PubMed2005

Infectious Aortitis.

Infection of the aorta usually results from septic embolization to the vasa vasorum, hematogenous seeding of an existing aneurysm, or extension from a contiguous site of infection. The diagnosis should be considered in patients, often men over the age of 50 years with atherosclerosis, who present with fever, abdominal pain, palpable abdominal mass, and leukocytosis, with or without positive blood cultures. In the pre-antibiotic area, infectious aortitis was largely a complication of infective endocarditis, and was usually caused by group A streptococci, Streptococcus pneumoniae, or Haemophilus influenzae. Now a diverse array of bacteria and fungi has been associated, most commonly Salmonella species, which comprise nearly one third of the abdominal aortic infections and Staphylococcus aureus. Computed tomography is the most useful imaging modality. Medical treatment alone carries a high mortality, whereas the mortality with surgery combined with antimicrobial treatment is lower. Empiric antibiotics effective against S. aureus and gram-negative rods, such as Salmonella, should be initiated in cases identified before microbiologic diagnosis. Surgical debridement and revascularization should be completed early because delay may lead to aneurysm rupture, which increases mortality. The intent of surgery is to 1) control hemorrhage, if the aneurysm has ruptured; 2) confirm the diagnosis; 3) control sepsis; and 4) reconstruct the arterial vasculature. The patient should remain on parenteral or oral antibiotics for at least 6 weeks, perhaps longer, to assure full eradication of the pathogen and prevent recurrent infection. Close medical follow-up is indicated and includes serial blood cultures and computed tomography scans.

Journal Article↗

PubMed2005

[1,2-13C2]-D-glucose profiles of the serum, liver, pancreas, and DMBA-induced pancreatic tumors of rats.

OBJECTIVES: In vitro stable isotope glucose tracer studies indicate that undifferentiated cells of the pancreas use glucose primarily through the nonoxidative reactions of the pentose cycle for nucleic acid ribose synthesis, whereas normal or less transformed cells primarily use the oxidative branch of the cycle. METHODS: The pancreatic heads of 4 groups (5/group) of male rats were implanted with time-release pellets designed to deliver placebo or 7,12-dimethylbenzanthracene (DMBA) at 11, 33, or 56 mg/d. Four weeks after pancreatic exposure to DMBA, [1,2-C2]-D-glucose tracer (1 g/kg) was injected intraperitoneally followed by sera collection at 1 and 2 hours and harvest of tumors, adjacent pancreatic tissue, and sera at 3 hours. RESULTS: Tumors (2-9 mm) were found across DMBA groups, with the largest in the high-dose group (> or =5 mm). Selective monitoring by gas chromatography-mass spectrometry of the doubly-labeled [1,2-C2]-D-ribose of RNA, which requires nonoxidative synthesis in the pentose cycle, showed a 2.8-, 2.9-, and 5.7-fold increase in pancreatic tumors. Liver and adjacent pancreas preferentially produced [1-C1]-D-ribose through the oxidative reactions of the cycle. Tumor-bearing animals also cleared and recycled tracer glucose at a faster rate. CONCLUSIONS: Simultaneous selective positional ion monitoring of C-labeled metabolites and their mass isotopomers in tissues and blood opens new avenues for the early detection and response to therapy testing of pancreatic cancer using GC-MS and/or magnetic resonance imaging-based methods. This study emphasizes the benefits of stable isotope-based dynamic metabolic profiling, when applied in vivo, and the several advantages it offers to positron emission tomography.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients.

BACKGROUND: Tigecycline is a broad-spectrum glycylcycline antibiotic being investigated for the treatment of serious infections in hospitalized patients. Tigecycline has been shown to be efficacious against serious infections in animals, and preliminary studies in healthy adults have shown that tigecycline has an acceptable tolerability profile. OBJECTIVE: This study compared the clinical and microbiological efficacy, pharmacokinetic properties, and tolerability of 2 doses of tigecycline in hospitalized patients with a complicated skin and skin-structure infection (cSSSI). METHODS: This Phase II, randomized, open-label study was conducted between September 1999 and March 2001 at 14 investigative centers across the United States. Patients were randomized to receive tigecycline 25 or 50 mg IV q12h for 7 to 14 days. The primary efficacy end point was the clinically observed cure rate among clinically evaluable (CE) patients at the test-of-cure visit. Secondary end points were the clinical cure rate at the end of treatment and bacteriologic response in microbiologically evaluable (ME) patients. Also, in vitro tests of susceptibility to tigecycline were performed for selected pathogens known to cause skin infections, including methicillin-resistant and methicillin-susceptible Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Tolerability assessments also were conducted. RESULTS: A total of 160 patients received > or =1 dose of tigecycline; 109 patients were CE, and 91 were ME. The majority of patients (74%) were men, and the mean (SD) age was 49.0 (14.8) years. At the test-of-cure visit, the clinical cure rate in the 25-mg group was 67% (95% CI, 53.3%-79.3%) and in the 50-mg group was 74% (95% CI, 60.3%-85.0%). In the 25-mg group, 56% of the patients had eradication (95% CI, 40.0%-70.4%) of the pathogens compared with 69% (95% CI, 54.2%-82.3%) in the 50-mg group. Values for the minimum concentration of tigecycline that is inhibitory for 90% of all isolates ranged from 0.06 to 0.50 microg/mL for the selected pathogens. Both tigecycline doses were generally well tolerated. Nausea and vomiting were the most common adverse events. CONCLUSIONS: In this study, tigecycline appeared efficacious and showed a favorable pharmacokinetic profile and an acceptable safety profile in the treatment of hospitalized patients with cSSSI. In patients who received 50-mg doses of tigecycline q12h, the clinical cure rates and microbial eradication rates were 74% and 70%, respectively, and were 67% and 56% in patients who received 25-mg doses.

Adolescent↗

PubMed2003

The challenge of pancreatic cancer.

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in men and women in the United States. It affects nearly as many people each year as does the human immunodeficiency virus and has a much worse outcome. This article reviews the progress in treatment of this disease since 1975, outlines the current clinical and research challenges in the field, and suggests a plan of action to address these challenges. The world literature in the field since 1975 was reviewed, and the pancreatic cancer Progress Report Group of the National Cancer Institute (NCI) is reviewed and presented. Some progress has been made in understanding and treating pancreatic cancer since 1975. Much remains to be done. The lack of progress in the field can largely be attributed to the lack of importance and subsequent lack of research dollars attributed to it by the NCI. The NCI is addressing this issue by proposing to fund Specialized programs of research excellence grants in pancreatic cancer. In addition, other mechanisms exist within the NCI to allow for additional funding of pancreatic cancer. Using the tremendous progress made in the field of human immunodeficiency virus research as an example, it is hoped that similar improvements can be made in the field of pancreatic cancer if substantial and sustained efforts are made.

Adenocarcinoma↗

PubMed2003

DNA ploidy and markovian analysis of neoplastic progression in experimental pancreatic cancer.

Computer-assisted analysis of DNA ploidy and nuclear morphology were used to elucidate changes in the cell nucleus that occur during the development of experimental pancreatic cancer. Ductal pancreatic adenocarcinoma was induced in 49 Syrian hamsters by SC injection of N-nitrosobis (2-oxopropyl) amine; twenty hamsters served as controls. Groups of animals were sacrificed every 4 weeks for 20 weeks and adjacent sections of pancreatic tissue were H&E and Feulgen-stained for light microscopy and computer assisted cytometry. Pancreatic ductal cells were classified as normal, atypical, or malignant; tissue inflammation (pancreatitis) was also noted when present. DNA ploidy and nuclear morphology evaluation (Markovian analysis) identified an atypical cell stage clearly distinguishable from either normal or malignant cells; pancreatitis preceded this atypia. The DNA ploidy histogram of these atypical cells revealed a major diploid peak and a minor aneuploid peak. The receiver operator characteristic curve areas for a logistic regression model of normal vs atypical cells was 0.94 and for atypical vs malignant was 0.98, numbers indicative of near-perfect discrimination among these three cell types. The ability to identify an atypical cell population should be useful in establishing the role of these cells in the progression of human pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Gene activity associated with cancers treated by surgical oncologists.

A significant component of the general surgeon's practice is treatment of cancer that most commonly involves breast, colorectal, pancreas, and hepatic surgeries. The prognosis for these patients is largely dependent upon the stage of the disease at the time of diagnosis. There is convincing evidence that the induction and progression of cancer occurs when the function of genes that regulate cell proliferation, cell death and DNA repair becomes altered. These molecular disturbances result from ongoing, tumor-promoting activity long before symptoms of the disease become apparent. The role of many genes and the extent of their involvement in this deleterious, molecular process is unique to the organ. However, the tumor suppressor genes p53 and p16, the oncogene c-myc, and the inflammation-associated enzyme COX-2 are implicated in all four of the tumors. The roles of the oncogenes ras and HER-2/erbB-2/neu are significant in all of the tumors except hepatocellular carcinoma. The systematic establishment of a comprehensive data base relating gene expression activity to the initiation and development of cancer will provide molecular markers for detection and targets for treatment. This overview presents the current status of information associating gene expression activity with cancers typically encountered by general surgeons.

Breast Neoplasms↗

PubMed2002

Increased expression of alpha-1-antitrypsin, glutathione S-transferase pi and vascular endothelial growth factor in human pancreatic adenocarcinoma.

BACKGROUND: This study was designed to investigate abnormalities in gene expression in ductal adenocarcinoma of the pancreas using cDNA arrays. METHODS: Gene expression in pancreatic ductal adenocarcinoma was compared with normal pancreatic tissue controls. Specimens from 5 patients with pancreatic adenocarcinoma were taken fresh at operation and analyzed using commercially prepared cDNA arrays evaluating approximately 2,000 genes. Immunohistochemical staining was used to confirm protein expression of selected genes. RESULTS: Alpha-1-antitrypsin (A1AT) and glutathione S-transferase pi (GSTP) were significantly up-regulated in all 5 tumors. Vascular endothelial growth factor (VEGF) was up-regulated in 4 of the 5 patients. Immunohistochemical staining verified the overexpression of each of these genes. CONCLUSIONS: A1AT, GSTP, and VEGF are overexpressed in human pancreatic adenocarcinoma specimens taken fresh at operation. To our knowledge, this is the first study of human pancreatic ductal adenocarcinoma demonstrating the up-regulation of these genes using gene expression arrays.

Adenocarcinoma↗

PubMed2002

Watershed events in the improvement of surgical outcomes in the elderly transplant (QLT) recipients.

The enactment of the Medicare legislation and the establishment of a National Institute for Aging in the 1960s and 1970s has spurred a number of developments which have proven to represent watershed advances in the surgical care of the elderly. The development of a multidisciplinary approach to both geriatric surgical care and research ultimately may prove to be the greatest advance yet seen.

Aged↗