Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to elucidate possible mechanisms responsible for the synergistic interaction between hyperthermia and melphalan observed in melanoma cells, we investigated the effect of heat on the formation and removal of melphalan-induced DNA interstrand cross-links (DNA ISC). Cells obtained from melanoma nodal metastases of 15 patients were grown as monolayer primary cultures and their malignant nature was confirmed by specific monoclonal antibodies. Cultures were treated with melphalan for 1 h at 37 or 42 degrees C and DNA ISC were determined by alkaline elution after proteinase K digestion. Results showed an enhanced induction of DNA ISC at hyperthermic conditions. Median number of DNA lesions 6 h after treatment was significantly higher for samples treated at 42 degrees C than for those treated at 37 degrees C (185 compared with 95 rad equivalents, p = 0.01). Moreover, the concomitant hyperthermic treatment prevented the long-term removal of DNA ISC produced by melphalan in most of the tumours considered.
 ...
PMID:Effect of hyperthermia on the formation and removal of DNA interstrand cross-links induced by melphalan in primary cultures of human malignant melanoma. 160 39

The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.
 ...
PMID:Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors. 1158 64

Vitronectin has been identified mainly as an adhesion protein that signals through uPAR and selected integrin receptors. In addition to its pro-adhesive properties, we identified recently vitronectin as a main chemoattractant present in diluted plasma/serum that directly stimulates migration of cancer cells. We also found that this pro-migratory activity of vitronectin can be quenched by fibrinogen. Based on this we hypothesized that this may explain preference of cancer cell to metastasize to fibrinogen-low microenvironments such as lymphatics or peritoneal cavity. Based on this, we decided to investigate a role of vitronectin in metastasis of ovarian cancer cells to peritoneal cavity. We tested migratory responsiveness of three human ovarian cancer cell lines to ascites isolated from ovarian cancer patients and characterize possible molecules involved in migration of ovarian cancer cells. The ascites samples were exposed to heat inactivation, proteinase K digested, dialyzed and charcoal stripped. We also performed cut-off filtration analysis and by employing ELISA assays to measure concentration of vitronectin in ascites fluid samples. Finally, we employed shRNA against uPAR and small molecular inhibitors of integrin receptors to assess their involvement in biological effects of vitronectin. From our studies, we found that the similarly to diluted plasma, vitronectin in absence of fibrinogen is a main chemotactic/chemokinetic protein present in ascites fluid. We also found that these pro-migratory properties of vitronectin can be quenched by addition of fibrinogen. Our studies also indicate that both uPAR and integrin receptors on ovarian cancer cells regulate migration of these cells to vitronectin gradient. In summary, we identified free soluble vitronectin as a potent direct chemoattractant for ovarian cancer cells and that its activity is suppressed after binding to fibrinogen. Since in ascites fluids vitronectin is present in free form because of a lack or low level of fibrinogen, this could explain preferences of ovarian cancer stem cells to metastasize within peritoneum. We propose that inhibitors which could sequester soluble vitronectin in similar fashion as fibrinogen, could be employed as a novel anti-metastatic drugs.
 ...
PMID:Vitronectin in the ascites of human ovarian carcinoma acts as a potent chemoattractant for ovarian carcinoma: Implication for metastasis by cancer stem cells. 2860 47