Analysis of p53 mutations in histologically normal lung tissues and lung tumors from non-small cell lung cancer patients.

Our previous study showed a characteristic p53 mutational spectrum in lung tumors from lung cancer patients in the Western Pennsylvania region. To further understand the involvement of p53 mutations in lung tumor development, in this study we compared p53 mutational spectra and distribution between tumor cells taken from lung tumor tissue and histologically normal cells taken from tumor-surrounding tissue obtained from 122 lung cancer patients [67 adenocarcinomas (ACs) and 55 squamous cell carcinomas (SCCs)]. Overall, mutations were detected in exons 5-8 of the p53 gene in cell samples from 39.

Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant.

We sought to determine the clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with post-transplant lymphoproliferative disorders (PTLDs). Eighty-four patients diagnosed with PTLDs between 1980 and 2004 at the University of Pittsburgh Medical Center were identified. Immunohistochemical staining was performed on tumor tissue at the time of diagnosis for the following proteins: Bcl-2, Bcl-6, c-myc and p53.

Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol.

Indices of renal injury and oxidative stress were examined in mice with deficiency of cytosolic Cu(2+)/Zn(2+) superoxide dismutase (SOD1-/-, KO) and their wild-type (WT) littermates with streptozotocin-induced diabetes. After 5 weeks of diabetes, KO diabetic (D) but not WT-D mice developed marked albuminuria, increases in glomerular content of transforming growth factor beta, collagen alpha1(IV), and nitrotyrosine, and higher glomerular superoxide compared with corresponding values in nondiabetics. After 5 months of diabetes, increases in these parameters, mesangial matrix expansion, renal cortical malondialdehyde content, and severity of tubulointerstitial injury were all significantly greater, whereas cortical glutathione was lower, in KO-D than in WT-D.

Parvovirus B19 infection in the immunocompromised host.

Human parvovirus B19 is a single-stranded DNA virus with a predilection for infecting rapidly dividing cell lines, such as bone marrow erythroid progenitor cells. People with defective cell-mediated immunity (eg, severe combined immunodeficiency syndrome; acquired immunodeficiency syndrome; and patients receiving immunosuppressive therapy, ie, post organ transplant) can develop pure red cell aplasia, in which suppression of erythroid precursors is permanent. Identification of parvovirus inclusions in marrow biopsies and subsequent confirmation of infection by in situ hybridization is important in the assessment of anemia in immunodeficient patients.

PPAR alpha agonists improve renal preservation in kidneys subjected to chronic in vitro perfusion: interaction with mannitol.

We developed methods for prolonged (12 h), sterile, normothermic perfusion of rat kidneys and screened compounds for renal preservation including: mitochondrial transition pore inhibitor (decylubiquinone); caspase inhibitor (Z-VAD); peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists (gemfibrozil, WY-14643); antioxidants (trolox, luteolin, quercetin); growth factors (HGF, PDGF, EGF, IGF-1, VEGF, transferrin); calpain inhibitor (Z-Val-Phe-CHO); calmodulin inhibitor (W7); K(ATP) opener (minoxidil, minoxidil sulfate); PARP inhibitor (3-aminobenzamide); calcium channel blocker (verapamil); V(2) agonist (DDAVP); diuretics (acetazolamide, hydrochlorothiazide, furosemide, mannitol); peroxisome proliferator-activated receptor-beta agonist (L-165041); dopamine agonist (dopamine); essential fatty acid (linolenic acid); beta-NAD; urea; uric acid; and aldosterone. In pilot studies, only PPARalpha agonists and mannitol provided promising results. Accordingly, these agents were investigated further.

Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion.

Background: Monocyte chemotactic protein-1 (MCP-1) plays a key role in the recruitment and activation of monocytes during inflammation. Increased MCP-1 serum levels in patients with various cancers were correlated with advanced stage. Here, we evaluated the role of MCP-1 on prostate cancer (CaP) cell proliferation and invasion.

Estradiol metabolites attenuate monocrotaline-induced pulmonary hypertension in rats.

Pulmonary arterial hypertension (PH) is a deadly disease characterized by pulmonary arterial vasoconstriction and hypertension, pulmonary vasculature remodeling, and right ventricular hypertrophy. Our previous in vivo studies, performed in several models of cardiac, vascular, and/or renal injury, suggest that the metabolites of 17beta-estradiol may inhibit vascular and cardiac remodeling. The goal of this study was to determine whether 2-methoxyestradiol (2ME), major non-estrogenic estradiol metabolite, prevents the development and/or retards the progression of monocrotaline (MCT)-induced PH.

Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic nitric oxide synthase inhibition.

Our previous studies in rodent models of nephropathy demonstrate that 2-hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity, exerts renoprotective effects. In vivo, 2HE is readily converted to 2-methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity. The goal of this study was to determine whether 2ME has renal and cardiovascular protective effects in vivo.

Proteomic analysis of mantle-cell lymphoma by protein microarray.

Mantle-cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma (NHL) that behaves aggressively and remains incurable. In order to understand the pathogenesis of MCL and design new therapies, it is important to accurately analyze molecular changes in pathways dysregulated in MCL. We used antibody microarrays to compare patterns of protein expression between CD19(+) purified B lymphocytes from normal tonsil and 7 cases of histologically confirmed MCL.

Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China.

Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations.

Analysis of p53 mutations in cells taken from paraffin-embedded tissue sections of ductal carcinoma in situ and atypical ductal hyperplasia of the breast.

Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood. In this study, we applied laser capture microdissection (LCM) microscope to histologically review and sample cells from paraffin-embedded breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS) and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected, using single stranded conformational polymorphism (SSCP) and sequencing, in cell samples of three cases with DCIS and five cases with ADH.

Attenuation of renal injury in db/db mice overexpressing superoxide dismutase: evidence for reduced superoxide-nitric oxide interaction.

The effects of overexpression of Cu(2+)/Zn(2+) superoxide dismutase-1 (SOD-1) on indexes of renal injury were compared in 5-month-old nontransgenic (NTg) db/db mice and db/db mice hemizygous for the human SOD-1 transgene (SOD-Tg). Both diabetic groups exhibited similar hyperglycemia and weight gain. However, in NTg-db/db mice, albuminuria, glomerular accumulation of immunoreactive transforming growth factor-beta, collagen alpha1(IV), nitrotyrosine, and mesangial matrix were all significantly increased compared with either nondiabetic mice or SOD-Tg-db/db.

Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice.

Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown.

Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco-related non-small cell lung cancer.

Lung cancer, a disease related mostly to tobacco smoke exposure and a leading cause of cancer-related death in industrialized countries, is frequently associated with mutations in the p53 tumor suppressor gene. Genetic differences resulting in inter-individual variation in DNA repair capacity may in part account for susceptibility of a cell to genotoxic agents leading to somatic mutations, including p53 mutations, and eventual transformation of a normal cell into a malignant phenotype. The objective of this study is to investigate the relationship between the polymorphisms of two DNA repair genes, the nucleotide excision repair xeroderma pigmentosum group D (XPD) gene (codons 312 and 751) and the base excision repair X-ray repair cross-complementing group 1 (XRCC1) gene (codon 399), and p53 mutations among lung cancer patients.

Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types.

The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size.

Expression of E2F-4 gene in colorectal adenocarcinoma and corresponding covering mucosa: an immunohistochemistry, image analysis, and immunoblot study.

E2F-4 is a transcription factor involved in the transition of the cell from the resting state (G0/G1) to the proliferative stage (S). It has been associated with the p107 and p130 members of the Rb-family and it is responsible for many important growth suppressive functions. E2F-1, one member of the E2F family, has a similar structure to E2F-4; however, both have different mechanisms of action in regulating cell-cycle progression.

FHIT protein expression and its relation to apoptosis, tumor histologic grade and prognosis in colorectal adenocarcinoma: an immunohistochemical and image analysis study.

The FHIT gene, a member of the histidine triad family has been identified as a tumor suppressor gene. Molecular genetic approaches to determine alterations in the FHIT gene in colorectal cancers have produced varying results with reported abnormalities of the FHIT gene transcripts in 13% to 50% of cases studied. FHIT has been reported to be involved in the regulation of apoptosis and cell cycle in cell culture systems.

Epidermoid cyst of the cecum of an elderly man with no previous history of surgery: a case report and review of literature.

Background: Pure, benign epidermoid cysts of the abdominal viscera are rare. There have been only four reports of epidermoid cysts of the cecum in the literature, two following appendectomies and attributed to the surgical procedure, and two in female patients, raising the possibility of dermoid cysts related to the ovaries.

Patients And Methods: We report the first case of epidermoid cyst of the cecum in an elderly man with no previous history of trauma or surgery, detected by computed tomography as an incidental finding of extraluminal cystic cecal mass.

Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes.

Previous studies demonstrated that 2 mo of dietary supplementation with alpha-lipoic acid (LA) prevented early glomerular injury in non-insulin-treated streptozotocin diabetic rats (D). The present study examined the effects of chronic LA supplementation (30 mg/kg body wt per d) on nephropathy in D after 7 mo of diabetes. Compared with control rats, D developed increased urinary excretion of albumin and transforming growth factor beta, renal insufficiency, glomerular mesangial matrix expansion, and glomerulosclerosis in association with depletion of glutathione and accumulation of malondialdehyde in renal cortex.

Effects of dietary supplementation of alpha-lipoic acid on early glomerular injury in diabetes mellitus.

Antioxidants, in particular vitamin E (VE), have been reported to protect against diabetic renal injury. alpha-Lipoic acid (LA) has been found to attenuate diabetic peripheral neuropathy, but its effects on nephropathy have not been examined. In the present study, parameters of glomerular injury were examined in streptozotocin diabetic rats after 2 mo on unsupplemented diets and in diabetic rats that received the lowest daily dose of dietary LA (30 mg/kg body wt), VE (100 IU/kg body wt), or vitamin C (VC; 1 g/kg body wt), which detectably increased the renal cortical content of each antioxidant.