Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

<p>Abstract</p> <p>Aim</p> <p>The aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.</p> <p>Methods</p> <p>23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.</p> <p>Results</p> <p>Histopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (> 2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.</p> <p>Conclusions</p> <p>Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.</p

Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons

The kinesin motor protein Kif1b has previously been implicated in the axonal transport of mitochondria and synaptic vesicles1,2. More recently kif1b has been linked with susceptibility to Multiple Sclerosis (MS) 3. Here we show that Kif1b is required for the localization of myelin basic protein mRNA to processes of myelinating oligodendrocytes in zebrafish. We observe the ectopic appearance of myelin-like membrane in kif1b mutants, coincident with the ectopic localization of myelin proteins in kif1b mutant oligodendrocyte cell bodies. These observations suggest the hypothesis that oligodendrocytes localize certain mRNA molecules, namely those encoding small basic proteins such as mbp, to prevent aberrant effects of these proteins elsewhere in the cell. We also find that Kif1b is required for outgrowth of some of the longest axons in the peripheral and central nervous systems. Our data demonstrate new functions of kif1b in vivo and provide insights into its possible roles in Multiple Sclerosis

The status of human papillomavirus and tumor suppressor genes p53 and p16 in carcinomas of uterine cervix from India

Objectives: Infection with the high-risk strain of human papillomaviruses (HPVs) and the inactivation of the tumor suppressor genep53through mutation are important factors in cervical carcinogenesis. To know whether such events would occur in cervical carcinomas of Indians, 43 tumors (consisting of 36 of stage III B and 6 of stage II B) were screened for p53 and p16gene mutations. Methods: PCR followed by single-strand conformation polymorphism (SSCP) analysis were used to detect mutations in p53andp16genes and PCR for the presence of human papillomavirus genome. HPV status was ascertained by PCR amplification of parts of E6 and E7 genes using primers pU-1M and pU-2R and typing was carried out by restriction analysis. Results: Of the 43 samples analyzed, 4 samples (9%) showed mobility shifts for p53 mutations; PCR products of thep16gene did not show band shifts in SSCP analysis. HPV DNA was detected in 70% of the 43 samples analyzed: HPV 16 in 23 cases (53%), HPV 18 in 4 cases (13.3%), and HPV 33 in 1 case (3.3%). Two amplified HPV DNAs that were difficult to type with various restriction enzymes were cloned and the amplified regions were sequenced. One of these was 93% close to HPV 35 and the other was 80% close to HPV 58. Three samples had both p53 mutations and HPV genome. Conclusions: Our results indicate that HPV 16 infection was more common than HPV 18, the p53 mutations and HPV infection were not mutually exclusive events in the genesis of carcinoma of uterine cervix among Indian women, andp16gene may not play a role in Indian cervical carcinomas

FHIT Gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas

Genetic alterations at the FHIT (fragile histidine triad) tumor suppressor gene have been found in various human cancers. We have made an attempt to find point mutations of this gene in two different cancers from India, with entirely different etiologic factors: oral cancer (55 samples) caused by chewing tobacco and cervical cancer (43 samples) caused mainly by HPV (human papilloma virus) infection. Analysis of tumor DNA by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method was performed on each of FHIT exons 5-9 individually, using exon-flanking primers. Two different mutations were identified in both oral and cervical tumors: one at the second nucleotide 3' to the termination codon (TGA) in exon 9 and the other at the ninth nucleotide upstream to the beginning of exon 9. These results indicate that mutations in the FHIT gene are rare events in these tumors in India (approximately 4%). In addition, we found a single nucleotide FHIT gene polymorphism which is due to T/A replacement at 17 nucleotides upstream to exon 9 where the A allele is 0.6 of the population

Online) An Open Access

ABSTRACT The present study was undertaken to detect the two genes, namely, Salmonella enterotoxin (stn) and plasmid encoded fimbrial (pef) genes, among clinical isolates of three Salmonella species from humans. A total of 176 isolate belonging to Salmonella enterica serovar Typhi (133), Salmonella enterica serovar paratyphi A (41) and Salmonella enterica serovar Typhimurium (2) serovars were analyzed by Polymerase Chain Reaction (PCR) using their specific primers for the detection of stn, and pef genes. Varying pattern of stn, and pef genes were observed amongst the isolates. While, stn was found in 140/176 (79.5%) Salmonella strains, the pef gene was not found in any of the tested strains. PCR findings indicated that the stn gene is widely distributed among Salmonella irrespective of the serovars and source of isolation