losartan-potassium and Precancerous-Conditions

To assess the effect of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) treatment on survival and leukemic transformation in myelodysplastic syndrome (MDS).. We compared the long-term outcome of patients with MDS treated with EPO plus G-CSF (n = 121) with untreated patients (n = 237) with MDS using multivariate Cox regression with delayed entry, for the first time adjusting for all major prognostic variables (WHO classification, karyotype, cytopenias, level of transfusion-need, age, and sex).. The erythroid response rate to EPO plus G-CSF was 39%, and the median response duration 23 months (range, 3 to 116+). In the multivariate analysis, treatment was associated with improved overall survival (hazard ratio, 0.61; 95% CI, 0.44 to 0.83; P = .002). Interestingly, this positive association was primarily observed in patients requiring fewer than 2 units of RBCs per month. Treatment was not linked to the rate of acute myeloid leukemia in any defined subgroup, including patients with an increase of marrow blasts or an unfavorable karyotype.. The inherent risk of leukemic evolution in MDS makes the current investigation highly relevant, in light of the recent reports of potential negative effects of EPO treatment on outcome in patients with cancer. We conclude that treatment of anemia in MDS with EPO plus G-CSF may have a positive impact on outcome in patients with no or low transfusion need, while not affecting the risk of leukemic transformation.

Topics: Aged; Anemia; Blood Transfusion; Cell Transformation, Neoplastic; Clinical Trials, Phase II as Topic; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Precancerous Conditions

Activation of the Wnt signaling pathway initiates the transformation of colorectal epithelial cells, although the transition to metastatic cancer requires angiogenesis. We have investigated the expression of the von Hippel-Lindau (VHL) tumor suppressor in the intestines from humans and mice. Here, we show that VHL expression is regulated by TCF4 and is restricted to the proliferative compartment at the bottom of intestinal crypts. Accordingly, VHL is completely absent from the proliferative intestinal pockets of Tcf4(-/-) perinatal mice. We observed complementary staining of the hypoxia-inducible factor (HIF) 1alpha to VHL in normal intestinal epithelium as well as in all stages of colorectal cancer (CRC). To the best of our knowledge, this is the first report demonstrating the presence of nuclear HIF1alpha in normoxic healthy adult tissue. Although we observed upregulated levels of VHL in very early CRC lesions from sporadic and familial adenomatous polyposis patients - presumably due to activated Wnt signaling - a clear reduction of VHL expression is observed in later stages of CRC progression, coinciding with stabilization of HIF1alpha. As loss of VHL in later stages of CRC progression results in stabilization of HIF, these data provide evidence that selection for VHL downregulation provides a proangiogenic impulse for CRC progression.

Topics: Adenocarcinoma; Adenoma; Adenomatous Polyposis Coli; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; beta Catenin; Cell Line; Cell Transformation, Neoplastic; Colon; Colonic Polyps; Colorectal Neoplasms; Disease Progression; Epithelial Cells; Erythropoietin; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intestinal Mucosa; Kidney; L Cells; Mice; Mice, Knockout; Neovascularization, Pathologic; Nerve Tissue Proteins; Precancerous Conditions; Promoter Regions, Genetic; Recombinant Fusion Proteins; Signal Transduction; TCF Transcription Factors; Transcription Factor 4; Transcription Factor 7-Like 2 Protein; Von Hippel-Lindau Tumor Suppressor Protein; Wnt Proteins; Wnt3 Protein

At birth, undescended testes contain germ cells, but after 1 year of life, a reduced number of germ cells is generally found. Microlithiasis and carcinoma-in-situ-testis occur in cryptorchid boys. Multinucleated germ cells, including at least 3 nuclei in the cell, exist in impaired spermatogenesis and in the senescent testis.. We investigated whether multinucleated spermatogonia were present in undescended testes of cryptorchid boys, and if such a pattern is associated with special clinical features.. Multinucleated spermatogonia occurred in 13/168 (8%) of 163 consecutive cryptorchid boys, who underwent surgery for cryptorchidism with simultaneous testicular biopsy showing seminiferous tubules. The patients with multinucleated spermatogonia more often exhibited a normal germ cell number (Fisher's exact test, p<0.0005), and were younger at surgery (Mann Whitney, p<0.005) than the rest of the patients. Before surgery, 3 patients underwent treatment with Erythropoietin because of renal failure. An intra-abdominal testis underwent clipping and division of the spermatic vessels, and a biopsy at final surgery 7 months later, exhibited multinucleated spermatogonia. In 1 case the undescended testicular position, a fixed retraction, was acquired after surgery for an inguinal hernia. Multinucleated spermatogonia were found in cases of carcinoma-in situ-testis in 2 cryptorchid boys. No case of multinucleated germ cells appeared in our normal material.. Multinucleated spermatogonia are a further abnormality present in cryptorchidism. The cryptorchid boys with multinucleated spermatogonia in general exhibited rather many germ cells. This feature may be associated with an increased risk of testicular malignancy later in life, and we propose a careful follow up regime in these cases including ultrasound examination and a testicular biopsy in cases of symptoms or clinical findings.

Topics: Biopsy; Carcinoma in Situ; Cell Nucleus; Child; Child, Preschool; Cryptorchidism; Erythropoietin; Humans; Infant; Male; Precancerous Conditions; Renal Insufficiency; Risk Factors; Spermatogonia; Testicular Neoplasms

Topics: Adrenal Gland Neoplasms; Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Erythropoietin; Heart Neoplasms; Hemochromatosis; Humans; Hypoglycemia; Iron; Liver; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Metastasis; Polycythemia; Precancerous Conditions