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Malignant Ascites (malignant + ascites)
Selected AbstractsCompact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotypeINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Katharine L. Sodek Abstract Ovarian cancer cells are present in malignant ascites both as individual cells and as multicellular spheroid aggregates. Although spheroid formation affords protection of cancer cells against some chemotherapeutic agents, it has not been established whether a relationship exists between invasive behavior and predisposition to spheroid formation. Aspects of spheroid formation, including cell-matrix adhesion, remodeling and contractility are characteristic myofibroblast-like behaviors associated with fibrosis that contribute to tumor growth and dissemination. We explored the possibility that cell behaviors that promote spheroid formation also facilitate invasion. Our analysis of 6 human ovarian cancer cell lines indicated that ovarian cancer cells possessing myofibroblast-like properties formed compact spheroids and invaded 3D matrices. These cells readily contracted collagen I gels, possessed a spindle-like morphology, and had elevated expression of genes associated with the TGF,-mediated fibrotic response and/or ,1 integrin function, including fibronectin (FN), connective tissue growth factor (CTGF/CCN2), lysyl oxidase (LOX1), tissue transglutaminase 2 (TGM2) and urinary plasminogen activator receptor (uPAR). Whereas cell aggregation was induced by TGF,, and by ,1-integrin overexpression and activation, these treatments did not stimulate the contractile activity required for spheroid compaction. The positive relationship found between compact spheroid formation and invasive behavior implies a preferential survival of an invasive subpopulation of ovarian cancer cells, as cells in spheroids are more resistant to several chemotherapeutics. Preventing the formation of ovarian cancer spheroids may represent a novel strategy to improve the efficacy of existing therapeutics. © 2008 Wiley-Liss, Inc. [source] Intracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2002YUKIO KAGEYAMA Abstract The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma. [source] Lysophosphatidic acid in malignant ascites stimulates migration of human mesenchymal stem cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Mi Jeong Lee Abstract Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and is involved in growth and invasion of ovarian cancer cells. Accumulating evidence suggests a pivotal role of mesenchymal stem cells (MSCs) or stromal cells in tumorigenesis. In the present study, we demonstrated that ascites from ovarian cancer patients and LPA increased migration of human MSCs. The migration of MSCs induced by LPA and malignant ascites was completely abrogated by pretreatment with Ki16425, an antagonist of LPA receptors, and by silencing of endogenous LPA1, but not LPA2, with small interference RNA, suggesting a key role of LPA played in the malignant ascites-induced migration. LPA induced activation of ERK through pertussis toxin-sensitive manner, and pretreatment of MSCs with U0126, a MEK inhibitor, or pertussis toxin attenuated the LPA-induced migration. Moreover, LPA induced activation of RhoA in MSCs, and pretreatment of the cells with Y27632, a Rho kinase inhibitor, markedly inhibited the LPA-induced migration. In addition, LPA and malignant ascites increased intracellular concentration of calcium in MSCs, and Ki16425 completely inhibited the elevation of intracellular calcium. These results suggest that LPA is a crucial component of the malignant ascites which induce the migration of MSCs and elevation of intracellular calcium. J. Cell. Biochem. 104: 499,510, 2008. © 2007 Wiley-Liss, Inc. [source] Gallbladder contractility in patients with cirrhotic versus malignant ascitesJOURNAL OF CLINICAL ULTRASOUND, Issue 8 2002Ramazan Sari MD Abstract Purpose The aim of this study was to evaluate differences in gallbladder contractility by measuring gallbladder wall thickness, fasting and residual gallbladder volume, and gallbladder ejection fraction in patients with cirrhotic and malignant ascites. Methods Twenty-four patients (16 women and 8 men) with malignant ascites (2 cervical, 2 colon, 2 stomach, 6 pancreatic, and 12 ovarian carcinomas), aged 59 ± 12 years, and 26 patients (14 women and 12 men) with cirrhotic ascites, aged 57 ± 16 years, were included in the study. After patients fasted overnight for 8 hours, gallbladder wall thickness, fasting gallbladder volume, and gallbladder volume and ejection fraction were measured sonographically at 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after ingestion of a standard liquid test meal. Results The mean gallbladder wall thickness was higher in patients with cirrhotic ascites than in those with malignant ascites (5.5 ± 1.5 mm [standard deviation] versus 3.1 ± 0.6 mm, respectively; p < 0.001). The mean fasting gallbladder volume was also higher in patients with cirrhotic ascites than in those with malignant ascites (27.3 ± 11.5 cm3 versus 17.6 ± 8.9 cm3; p < 0.05). Patients with cirrhotic ascites had significantly higher mean postprandial gallbladder volumes and ejection fractions than did those with malignant ascites at all times except 10 minutes after the meal (p < 0.05). Conclusions Our findings suggest that gallbladder contractility is greater in patients with cirrhotic ascites than in patients with malignant ascites. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:477,480, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10108 [source] Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat gastric cancer with ascites and/or peritoneal carcinomatosis: Results from a Chinese centerJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2010Xiao-Jun Yang MD Abstract Background This work was to evaluate cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). Methods CRS and HIPEC were performed on 28 GC patients with peritoneal carcinomatosis (PC) and/or malignant ascites, with survival and perioperative safety as study endpoints. Results A total of 30 CRS and HIPEC procedures were performed. Cytoreduction scores ratings (CCR) were CCR-0 in 11 (39.2%), CCR-1 in 6 (21.4%), CCR-2 in 8 (28.8%), and CCR-3 in 3 (10.6%) cases. The 6-, 12-, 18-, and 24-month survival rates were 75%, 50%, 43%, and 43%, respectively. The median survivals of patients with PCI ,20 and high PCI >20 were 27.7 months (95% CI 15.2,40.3 months) and 6.4 months (95% CI 3.8,8.9 months) (P,=,0.000). The estimated median survival for patients with CCR-0, CCR-1, and CCR-2 and 3 were 43.4 months (95% CI, 26.9,59.9 months), 9.5 months (95% CI 6.4,12.6 months), and 7.5 months (95% CI 3.0,13.6 months) (P,=,0.001, CCR0 vs. CCR1-3). No perioperative death but 1 (3.6%) serious adverse event occurred. Conclusions CRS plus HIPEC could offer survival advantage for selected GC patients with PC and/or ascites, with acceptable safety profile. J. Surg. Oncol. 2010; 101:457,464. © 2010 Wiley-Liss, Inc. [source] Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinomaLIVER TRANSPLANTATION, Issue 3 2000Ilja De Vreede Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma. [source] Proteomic profiling of exosomes: Current perspectivesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2008Richard J. Simpson Professor Abstract Exosomes are 40,100,nm membrane vesicles of endocytic origin secreted by most cell types in vitro. Recent studies have shown that exosomes are also found in vivo in body fluids such as blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, and breast milk. While the biological function of exosomes is still unclear, they can mediate communication between cells, facilitating processes such as antigen presentation and in trans signaling to neighboring cells. Exosome-like vesicles identified in Drosophila (referred to as argosomes) may be potential vehicles for the spread of morphogens in epithelia. The advent of current MS-based proteomic technologies has contributed significantly to our understanding of the molecular composition of exosomes. In addition to a common set of membrane and cytosolic proteins, it is becoming increasingly apparent that exosomes harbor distinct subsets of proteins that may be linked to cell-type associated functions. The secretion of exosomes by tumor cells and their implication in the transport and propagation of infectious cargo such as prions and retroviruses such as HIV suggest their participation in pathological situations. Interestingly, the recent observation that exosomes contain both mRNA and microRNA, which can be transferred to another cell, and be functional in that new environment, is an exciting new development in the unraveling exosome saga. The present review aims to summarize the physical properties that define exosomes as specific cell-type secreted membrane vesicles. [source] Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2010Peter Ruf WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The trifunctional antibody catumaxomab is a highly effective anti-cancer therapeutic that is administered to patients suffering from malignant ascites intraperitoneally (i.p.) in microgram (µg) doses. So far, no clinical pharmacokinetic data are available. WHAT THIS STUDY ADDS , Catumaxomab attains effective local concentrations in the ascites fluid and shows low systemic exposure with an acceptable safety profile confirming the appropriateness of the i.p. application scheme. AIMS Catumaxomab is the first EMEA approved trifunctional anti-EpCAM×anti-CD3 antibody for the treatment of cancer patients with malignant ascites. A phase II pharmacokinetic study was conducted to determine local and systemic antibody concentrations and anti-drug antibody (ADA) development. METHODS Thirteen cancer patients with symptomatic malignant ascites were treated with four ascending doses of 10, 20, 50, and 150 µg catumaxomab intraperitoneally (i.p.) infused on days 0, 3, 6 or 7 and 10. The pharmacokinetics of catumaxomab were studied by implementation of supportive data from a non clinical mouse tumour model. Additionally, ADA development was monitored. RESULTS Ten out of 13 patients were evaluable for pharmacokinetic analysis. Catumaxomab became increasingly concentrated in ascites during the course of treatment, attaining effective concentrations in the ng ml,1 range. Catumaxomab remained immunologically active even after several days in the circulation. The observed systemic catumaxomab exposure was low (<1%), with a maximal median plasma concentration (Cmax) of 403 pg ml,1. The mean elimination half-life in the plasma was 2.13 days. All patients developed ADA, but not before the last infusion. High observed inter-individual variability and low systemic exposure may be explained by the inverse correlation between tumour burden, effector cell numbers and systemic antibody bioavailability as demonstrated in a defined mouse tumour model. CONCLUSIONS Based on the high and effective local concentrations, low systemic exposure and acceptable safety profile, we confirmed that the i.p. application scheme of catumaxomab for the treatment of malignant ascites is appropriate. [source] Identification of oligopeptides binding to peritoneal tumors of gastric cancerCANCER SCIENCE, Issue 10 2006Noriyuki Akita This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor-associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor-selective binding peptides. Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for ,3,1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer. (Cancer Sci 2006; 97: 1075,1081) [source] | ||||||||||