Search

Primary carcinomas of the vagina are rare tumors, accounting for 2%–3% of all gynecologic malignancies. Only a few karyotypes based on chromosome banding techniques have been reported. We have, therefore, used comparative genomic hybridization to establish a pattern of genomic imbalances in vaginal squamous cell carcinomas. Analysis of 16 formalin-fixed and paraffin-embedded tumors revealed that 70% of vaginal carcinomas carry relative copy number increases that map to chromosome arm 3q. Other recurring gains were observed on chromosome arms 5p and 19p. Chromosomal losses were infrequent. Most tumors were aneuploid, as measured by image cytometry on Feulgen-stained tissue sections. The cytogenetic data were related to the presence of human papillomavirus genomes, expression of laminin-5 as a marker for invasiveness, and expression levels of markers for proliferative activity and mutated TP53. All relevant clinical data were recorded. The results suggest that vaginal carcinomas are defined by a specific distribution of chromosomal aneuploidies and that the pattern of genomic imbalances is strikingly similar to that observed in squamous cell carcinomas of the uterine cervix. Age at diagnosis (P = 0.031), tumor size (P = 0.025), and increased laminin-5 expression (P = 0.006) have a significant influence on the survival time. [Copyright &y& Elsevier]

Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis–associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis–associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P = 0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis–associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before. [Copyright &y& Elsevier]

Abstract Chromosomal aneuploidy is a defining feature of carcinomas and results in tumor-entity specific genomic imbalances. For instance, most sporadic colorectal carcinomas carry extra copies of chromosome 7, an aneuploidy that emerges already in premalignant adenomas, and is maintained throughout tumor progression and in derived cell lines. A comprehensive understanding on how chromosomal aneuploidy affects nuclear organization and gene expression, i.e., the nucleome, remains elusive. We now analyzed a cell line established from healthy colon mucosa with a normal karyotype (46,XY) and its isogenic derived cell line that acquired an extra copy of chromosome 7 as its sole anomaly (47,XY,+7). We studied structure/function relationships consequent to aneuploidization using genome-wide chromosome conformation capture (Hi-C), RNA sequencing and protein profiling. The gain of chromosome 7 resulted in an increase of transcript levels of resident genes as well as genome-wide gene and protein expression changes. The Hi-C analysis showed that the extra copy of chromosome 7 is reflected in more interchromosomal contacts between the triploid chromosomes. Chromatin organization changes are observed genome-wide, as determined by changes in A/B compartmentalization and topologically associating domain (TAD) boundaries. Most notably, chromosome 4 shows a profound loss of chromatin organization, and chromosome 14 contains a large A/B compartment switch region, concurrent with resident gene expression changes. No changes to the nuclear position of the additional chromosome 7 territory were observed when measuring distances of chromosome painting probes by interphase FISH. Genome and protein data showed enrichment in signaling pathways crucial for malignant transformation, such as the HGF/MET-axis. We conclude that a specific chromosomal aneuploidy has profound impact on nuclear structure and function, both locally and genome-wide. Our study provides a benchmark for the analysis of cancer nucleomes with complex karyotypes. [ABSTRACT FROM AUTHOR]

Abstract: Stem cells derived from pancreatic tissue are well characterized and exhibit a broad plasticity as they can differentiate beyond lineage boundaries into many cell types. The aim of this study was the comparative characterization of pancreatic stem cells with one other derivate of the embryonic foregut, namely salivary glands, for the existence of similar stem cell populations. The expression of stem cell markers as well as lineage-specific markers was detected by reverse transcription polymerase chain reaction, flow cytometry and immuncytochemical staining. The isolated cells from salivary glands and pancreas grew adherently in vitro and could be maintained for up to 55 and 46 population doublings, respectively. Cells from both tissues showed a comparable phenotype. They expressed different embryonic and adult stem cell markers and had the ability to differentiate spontaneously into cells representing the three embryonic germ layers. Additionally, the directed differentiation of glandular stem cells into the mesodermal lineage was achieved, yielding adipogenic, osteogenic and chondrogenic cells from salivary gland stem cells as well as osteogenic and chondrogenic cells from pancreatic stem cells. Here, we compared two stem cell populations from different glandular tissues which showed similar phenotypes and analogous properties. During embryonic development the two exocrine glands originate from the foregut, which might be the explanation for these intriguing resemblances. [Copyright &y& Elsevier]

Background and Purpose: To this day, the diagnostic and therapeutic strategy for acute lower gastrointestinal hemorrhage requiring transfusion varies among different hospitals. The purpose of this paper was to evaluate our own data on the group of patients presented and to outline our diagnostic and therapeutic regime taking into account the literature of the past 30 years.Methods: Following prospective data collection on 63 patients of a university hospital (40 male, 23 female patients) who received surgical intervention for acute lower intestinal hemorrhage requiring transfusion, we retrospectively analyzed the data. After a medical history had been taken, all patients underwent clinical examination, including digital palpation; 62 patients underwent procto-rectoscopy, 38 gastroscopy and colonoscopy, 52 patients colonoscopy only, and 45 patients gastroscopy only. Angiography was applied in 14 cases and scintigraphy in 20 cases.Results: Diagnostic procedures to localize hemorrhage were successful in 61 cases, 41 of which through endoscopy, 12 through angiography, and eight through scintigraphy. Of our group of patients, 32 suffered from a bleeding colonic diverticulum, eight from angiodysplasia, and five from bleeding small bowel diverticula. Five patients had inflammatory bowel disease and three neoplasia. Among the surgical interventions, segmental resections were performed most frequently (15 sigmoidectomies, 11 small bowel segmental resections, 11 left hemicolectomies, seven right hemicolectomies, one proctectomy). Subtotal colectomies were carried out in ten cases. The complication rate for this group of critically ill, negatively selected patients was 60.3% and the mortality rate was 15.9%.Conclusions: Examination and stabilization of the patient is directly followed by diagnostic localization. Today, we primarily rely on nonsurgical control of hemorrhage by endoscopy or angiography; the indication for surgery is mainly limited to peracute, uncontrollable, and recurrent forms. In the case of surgery, intestinal segmental resection is recommended after identification of the lesion; if the localization of colonic hemorrhage is uncertain, subtotal resection is the method of choice. For stable patients with unverifiable small-bowel hemorrhage we recommend regular re-evaluation. [ABSTRACT FROM AUTHOR]