c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma.
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Hepatocyte growth factor (HGF) plays important roles in tumor development and progression. It is currently thought that the main action of HGF is of a paracrine nature: HGF produced by mesenchymal cells acts on epithelial cells that express its receptor c-MET. In this investigation, we explored the significance of c-MET expression in myofibroblasts, both in culture and in patients with lung adenocarcinoma. We first showed that human myofibroblasts derived from primary lung cancer expressed c-MET mRNA and protein by reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of myofibroblasts was stimulated in a dose-dependent manner by exogenously added recombinant human HGF whereas it was inhibited in a dose-dependent manner by neutralizing antibody to HGF. The addition of HGF in the culture medium stimulated tyrosine phosphorylation of c-MET. The c-MET protein was immunohistochemically detected in myofibroblasts in the invasive area of lung adenocarcinoma. Finally, the prognostic significance of c-MET expression in stromal myofibroblasts was explored in patients with small-sized lung adenocarcinomas. c-MET-positive myofibroblasts were observed in 69 of 131 cases (53%). A significant relationship between myofibroblast c-MET expression and shortened patient survival was observed in a whole cohort of patients including all pathological stages (two-sided P: = 0.0089 by log-rank test) and in patients with stage IA disease (two-sided P: = 0.0019 by log-rank test). These data suggest that the HGF/c-MET system constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This autocrine system may play a role in invasion and metastasis of lung adenocarcinoma. (+info)
Extradural approach to the lateral sellar compartment.
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This paper describes an extradural approach to the lateral sellar compartment (LSC, cavernous sinus), which represents a refinement of the original work performed on this topic by Parkinson, Dolenc, and Hakuba, and other enthusiastic neurosurgeons. This detailed description of the extradural approach is based on the dissection of 30 cadaver specimens and surgical experience of 110 LSC lesions. The extradural approach is based on the developmental anatomy of the LSC, and provides: (1) complete exposure of the entire LSC; (2) excellent control of the intracavernous carotid artery; (3) easier identification and less injury of the cranial nerves; (4) reduced brain damage with limited extradural retraction; (5) preserving the Sylvian vein and the sphenoparietal sinus; (6) minimal intradural blood spillage; (7) shorter operative time; (8) physiological reconstruction of the lateral wall to prevent CSF leakage; and (9) access to the contralateral LSC. As the LSC is an extradural space, the extradural approach may be safely employed to access lesions involving the LSC. (+info)
Laparoscopic intracorporeal bowel resection with ultrasound versus electrosurgical dissection.
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BACKGROUND AND OBJECTIVES: We assessed resection time and collateral thermal tissue damage of ultrasonically activated surgery (UAS) and high-frequency blade-enhanced bipolar electrosurgery (BE) in laparoscopic bowel surgery. METHODS: We compared UAS laparoscopic intracorporeal small bowel mesentery re-section with an equivalent procedure performed with BE in a porcine model. Resection was defined as 12 end-arcade arteries supplying the intended bowel segment. Vessels were divided one cm off the bowel wall. Aside from shaft diameter, jaws gaping pattern, and cutting blade length, UAS and BE devices were well matched for handle ergonomics, jaws gaping extent, power setting, type of use, working shaft axial rotation, and length. A pathologist blind to the method used assessed the collateral thermal damage. Resections were allocated to either method by computer-generated block randomization. The study design was sequential triangular with a 5% significance level and 90% power. RESULTS: No significant differences occurred in intraoperative blood pressure and heart rate variations in pigs undergoing UAS or BE. Median operating time (measured after 10, 20, and 30 resections in each study arm) was significantly shorter in UAS than in BS (0.57 vs. 2.01 min P < 0.001). Histology of small bowel wall specimens revealed no collateral thermal damage. CONCLUSIONS: UAS laparoscopic bowel surgery offers reduced resection time as com-pared with its BE counterpart in a porcine model. (+info)
Cadaveric dissection for the rectal surgeon.
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The benefits of total mesorectal excision are due to the complete excision of the mesorectum with preservation of the pelvic autonomic nerve plexuses, the hypogastric nerves and nervi erigentes. Several important structures are incompletely seen at operation, and cadaveric dissection of an intact lower trunk and a sagittally hemisected pelvis is a valuable exercise in demonstrating them. A method for dissection is described which illustrates the key anatomical points. (+info)
Alterations of gene expression during colorectal carcinogenesis revealed by cDNA microarrays after laser-capture microdissection of tumor tissues and normal epithelia.
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To identify a set of genes involved in the development of colorectal carcinogenesis, we compared expression profiles of colorectal cancer cells from eight tumors with corresponding noncancerous colonic epithelia using a DNA microarray consisting of 9216 human genes. These cell populations had been rendered homogeneous by laser-capture microdissection. Expression change in more than half of the tumors was observed for 235 genes, i.e., 44 up-regulated and 191 down-regulated genes. The differentially expressed genes include those associated with signal transduction, metabolizing enzymes, production of reactive oxygen species, cell cycle, transcription, mitosis, and apoptosis. Subsequent examination of 10 genes (five up-regulated and five down-regulated) by semiquantitative reverse transcription-PCR using the eight tumors together with an additional 12 samples substantiated the reliability of our analysis. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of colorectal carcinogenesis and represents a source of novel targets for cancer therapy. (+info)
cAMP-dependent fluid secretion in rat inner medullary collecting ducts.
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We used an unambiguous in vitro method to determine if inner medullary collecting ducts (IMCD) have intrinsic capacities to absorb and secrete solutes and fluid in an isotonic medium. IMCD(1), IMCD(2), and IMCD(3) were dissected from kidneys of young Sprague-Dawley rats. 8-Bromo-3',5'-cyclic monophosphate (8-BrcAMP) stimulated lumen formation and progressive dilation in all IMCD subsegments; lumen formation was greatest in IMCD(1.) Benzamil potentiated the rate of lumen expansion in response to 8-BrcAMP. Fluid entered tubule lumens by transcellular secretion rather than simple translocation of intracellular fluid. Secreted lumen solutes were osmometrically active. Inhibition of protein kinase A with H-89 and Rp diastereomer of adenosine 3',5'-cyclic monophosphorothioate blocked fluid secretion. The rate of lumen expansion was reduced by the selective addition of ouabain, barium, diphenyl-2-carboxylate, bumetanide, glybenclamide, or DIDS, or reduction of extracellular Cl(-). We conclude that IMCD absorb and secrete electrolytes and fluid in vitro and that secretion is accelerated by cAMP. We suggest that salt and fluid secretion by the terminal portions of the renal collecting system may have a role in modulating the composition and volume of the final urine. (+info)
Mutational analysis of the 5' noncoding region of the bcl-6 gene in primary gastric lymphomas.
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Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements. Most of the primary gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marginal zone cells. However, bcl-6 protein expression was identified in high-grade gastric lymphomas, suggesting its role in high-grade transformation. In this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascertain the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas. A total 31 cases of gastric lymphoma were classified into low-grade gastric lymphomas of MALT type (n = 13), high-grade gastric lymphomas of MALT type (n = 6) and gastric diffuse large B-cell lymphomas (n = 12). Bcl-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymphomas. In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low- and high-grade components demonstrated the same frequency (3/6, 50%) of mutations. The tissue obtained from the marginal zone of Peyer's patch by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 mutations by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas. (+info)
Whole genome amplification and high-throughput allelotyping identified five distinct deletion regions on chromosomes 5 and 6 in microdissected early-stage ovarian tumors.
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Investigation of genetic changes in tumors by loss of heterozygosity is a powerful technique for identifying chromosomal regions that may contain tumor suppressor genes. In this study, we determined allelic loss on chromosomes 5 and 6 in 29 primary early-stage epithelial ovarian carcinomas including 3 microscopically identified adenocarcinomas using a high-throughput PCR-based method combined with laser capture microdissection and whole genome amplification techniques. Twenty microsatellite markers spanning chromosomes 5 and 6 at an average distance of 20 cM were examined. High frequencies of loss on chromosome 5 were identified at loci D5S428 (48%), D5S424 (32%), and D5S630 (32%). Our study also showed that chromosome 6 exhibited high frequencies of loss of heterozygosity at loci D6S1574 (46%), D6S287 (42%), D6S441 (45%), D6S264 (60%), and D6S281 (35%). These results suggest that multiple tumor suppressor genes are located on five distinct regions on chromosomes 5 and 6, i.e., 5p15.2, 5q13-21, 6p24-25, 6q21-23, and 6q25.1-27, and may be involved in the early development of ovarian carcinomas. (+info)