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Intraperitoneal recombinant interferon-alpha 2b for recurrent malignant ascites due to ovarian cancer.

Thirteen patients with malignant ascites due to recurrent ovarian cancer were treated with intraperitoneal interferon 2b (5 mu/m2 escalating to 15 mu/m2, administered twice weekly by indwelling intraperitoneal catheter). The study population included eight patients with ascites only and five patients with ascites plus tumor masses greater than 2 cm in diameter. Five of 13 responded to treatment. All the responses were seen in patients with ascites only. Although tumor mass was an important determinant of response there was also a correlation between clinical response and suppression of colony growth on soft agar after in vitro exposure of tumor cells to interferon-alpha (IFN alpha). The intraperitoneal use of IFN alpha should be explored further in tumors with a predominant intraperitoneal location and microimplantation growth pattern.

Ascites↗

Ascites levels of haptoglobin in patients with ovarian cancer.

BACKGROUND: Haptoglobin is an acute-phase reactant protein involved in immune regulation. It has been isolated from malignant ovarian ascites and has been shown to be capable of mediating nonspecific immune suppression in vitro in humans and in vivo in experimental animals. The range of concentrations under which such a nonspecific suppression is observed lies well within concentrations of haptoglobin observed in vivo. This immune suppression could adversely affect patient outcome. METHODS: Based on this information, ascites haptoglobin levels of 21 consecutive patients with ovarian cancer who underwent initial surgical debulking were determined. After the patients received chemotherapy, they were divided into those having a positive and those have a negative second-look operation. RESULTS: Seventeen patients with positive pathology at second look had an initial mean ascites haptoglobin level of 99 +/- 49 mg/dl. The mean haptoglobin level in the four patients with negative findings was 67 +/- 42 mg/dl. The difference in these mean haptoglobin levels is not statistically significant (P > 0.05). CONCLUSION: Although the number of patients in this study is small, the wide range of values documented in both groups make it doubtful that an initial absolute ascites haptoglobin level will prove clinically prognostic of eventual disease status at the time of second look laparotomy.

Adenocarcinoma↗

Peritoneovenous shunting for nongynecologic malignant ascites.

BACKGROUND: The development of malignant ascites has been associated with a poor prognosis. Previous reports have documented high morbidity rates associated with placement of palliative peritoneovenous shunts (PVS). Most study series have included gynecologic malignancies in their analysis, and wide variations in survival time have been reported. Reported data from nongynecologic malignancies and identification of preoperative factors associated with improved outcome were the concerns of the current study, which attempted to identify patients with malignant ascites who might have benefitted from PVS. METHODS: A retrospective chart review was performed and data including age, gender, weight, preoperative laboratory values, cytology on peritoneal fluid aspirates, and complications within 30 days of the operative procedure were obtained and recorded. Discharge date and follow-up status were obtained for all patients. Statistical analysis was done for categorical values by comparing survival times from date of procedure with follow-up times using the log rank test. Significance for numeric values was determined with Cox regression analysis. Multivariate analysis using Cox regression was performed for those values found to be significant on univariate analysis. RESULTS: Fifty- five patients who had undergone PVS from 1980-1996 for ascites on the Gastric and Mixed Tumor service at the Memorial Sloan-Kettering Cancer Center were identified. Two patients with benign disease and two patients with ovarian malignancies were excluded. The remaining 51 patients underwent placement of 53 PVSs for palliation. Median survival time for the entire group was 52 days. Univariate analysis identified preoperative blood urea nitrogen (BUN), creatinine (Cr), BUN to Cr ratio, and diagnosis as significant factors. Preoperative BUN emerged as an independent predictor of survival by multivariate analysis, and those patients who had a BUN value of < = 17 demonstrated a survival advantage over those with a BUN of > 17. The assessable palliation factors were hospital discharge (80% of patients) and weight loss after shunting (68% of patients lost > 1 kg). Ninety-six percent of patients (24 of 25) with a preoperative BUN of < or = 17 were discharged. CONCLUSIONS: The development of nongynecologic malignant ascites is an end stage event for most patients. The placement of PVS for those patients with nongastrointestinal tumor etiologies, a BUN of < 17, a Cr of < or = 1.1, and a BUN to Cr ratio of < 19 yielded the best results. In the current study, palliation was difficult to assess accurately, although most patients were discharged or lost > 1kg of weight after shunting.

Adult↗

Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma.

Urinary trypsin inhibitor (UTI; Mr 40 kDa) is a Kunitz-type protease inhibitor that efficiently inhibits cell-associated trypsin and plasmin activities. The aim of this study is to examine the expression pattern of UTI in the human ovarian carcinoma ascites fluid by Western blotting, zymography, immunoprecipitation, immunohistochemistry, biochemical and gene analyses and animal experiments. We have identified and characterized the 40 kDa immunoreactive UTI (UTI(40)) and 8 kDa degradation fragment (UTI(8)) in ascites fluid. The levels of UTI(40) and UTI(8) are elevated in ascites fluid taken from patients with ovarian carcinoma relative to paired plasma samples. The UTI(40) and UTI(8) were identified immunologically by the reactivity with 2 different anti-UTI antibodies recognizing different epitopes of the UTI molecule, functionally by its ability to bind trypsin and structurally by its apparent molecular mass with and without deglycosylation treatment. The purified polypeptides have been sequenced and were identical with sequences obtained from UTI and the carboxyl-terminal domain of UTI, respectively. However, UTI mRNA was not detected in the ovarian carcinoma tissue and ovarian carcinoma cell lines examined. Based on extravasation experiments using intravenously injected biotinylated inter-alpha-trypsin inhibitor (IalphaI; a precursor of UTI), we conclude that UTI(40) and UTI(8) found in the ascites fluid may result from (i) the extravasation of plasma proteins such as IalphaI into the peritoneal cavity via hyperpermeable vessels and (ii) the subsequent degradation of IalphaI and UTI(40) by tumor cell-associated trypsin-like enzymes.

Adenocarcinoma, Clear Cell↗

Aetiology and treatment of chylous ascites.

A series of 45 patients with chylous ascites has been reviewed. The age at presentation ranged from 1 to 80 (median 12) years; 23 patients were aged < or = 15 years. Thirty-five patients had an abnormality of the lymphatics (primary chylous ascites); in the remaining ten, the ascites was secondary to other conditions, principally non-Hodgkin's lymphoma (six patients). Two principal mechanisms of ascites formation were identified using lymphangiography and inspection at laparotomy: leakage from retroperitoneal megalymphatics, usually through a visible lymphoperitoneal fistula (14 patients); and leakage from dilated subserosal lymphatics of the small intestine, invariably associated with leaking lacteals causing protein-losing enteropathy (24 patients). Both sites of leakage were present in a further five patients. In the remaining two patients, chyle was leaking from normal mesenteric lymphatics, in one via a ruptured mesenteric lymph cyst and in the other from the site of a previous lymph node biopsy. Other associated lymphatic abnormalities were present in 36 patients, lymphoedema of the leg being the commonest (26 patients). All patients were initially treated conservatively with dietary manipulation; this was the most satisfactory treatment for those with leaking small bowel lymphatics. Surgery (fistula closure, bowel resection or insertion of a peritoneovenous shunt) was performed in 30 patients. Closure of a retroperitoneal fistula, when present, was the most successful operation, curing seven of the 12 patients so treated.

Adolescent↗

Immunocytochemical detection using CDX2: An aid for discerning tumor involvement in ascites cytology.

BACKGROUND: Although ascites cytology is important for therapeutic strategies, it is difficult to distinguish cancer infiltration from reactive mesothelial proliferation in some patients. In this study, the authors applied CDX2 immunocytochemistry to improve diagnostic accuracy. METHODS: The authors examined the distribution of CDX2 expression in carcinoma specimens using paraffin-embedded tissues from various organs from 549 cancer patients. CDX2 immunostaining was applied to the 116 ascites specimens. RESULTS: CDX2 expression was detected in a restricted range of cancers, with the vast majority of them originating from the gastrointestinal tract and pancreas. When applied to ascites specimens, no positive reactions were detected in any of the 81 cytology-negative and molecular genetic analysis-negative specimens. By contrast, 28 of 35 specimens diagnosed as suspicious for malignancy or malignancy showed a positive reaction. Furthermore, the authors found that a nuclear-positive reaction was easily evaluated, even with a high level of background staining, and single cancer cells in 10(6) normal cells could be detected. CONCLUSION: Results suggest that CDX2 is a specific and sensitive marker to detect gastrointestinal and pancreatic malignancies in ascites cytology.

Adenocarcinoma↗

Ciliated ovarian adenocarcinoma cells in ascitic fluid cytology: report of a case with immunocytochemical features.

A case of ovarian serous adenocarcinoma presenting with ascitic fluid is reported. Cytology of the ascitic fluid showed the presence of cilia on most of malignant tumor cells. These tumor cells occurred singly; cilia usually appeared in unipolar locations. Immunocytochemical studies were performed on the ascitic fluid samples as well as tissue sections. CA19-9, CA125, CA50, and epithelial antigens were positive, while carcinoembryonic antigen was negative. The positive reactions were characteristic for cilia of the tumor cells. The findings also emphasize that positive reaction of these markers will usually exclude a noncommon epithelial tumor, but will not distinguish between benign and malignant ovarian tumors. Report of cilia-bearing tumor cells in ascitic fluid are few; no one, to the best of our knowledge, has previously documented the immunocytochemistry of these tumor cells.

Adenocarcinoma↗

Culture-negative neutrocytic ascites: a variant of spontaneous bacterial peritonitis.

A review of the medical records of patients diagnosed as having "spontaneous bacterial peritonitis" (SBP) revealed 18 episodes of culture-negative neutrocytic ascites (CNNA) in 17 patients. The following criteria were all required in order to qualify for this diagnosis: (i) an ascitic fluid neutrophil count greater than 500 cells per mm3; (ii) negative ascitic fluid culture (5); (iii) absence of an intraabdominal source of infection; (iv) no antibiotic treatment within 30 days, and (v) no evidence of pancreatitis. Five patients had positive blood cultures. Two patients with CNNA had SBP in the past, and two other patients, who survived the episode of CNNA, subsequently developed SBP. Clinical signs and symptoms of patients with CNNA were not different from those of 32 patients with 33 episodes of culture-positive SBP. The mortality of CNNA (50%) was not different from that of SBP (70%). Because of the high mortality and because of the similarity of CNNA to SBP, it is presumed that many patients with CNNA have bacterial infection of their ascitic fluid, and it is recommended that they be treated with antibiotics.

Ascites↗

Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations.

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.

Acute Disease↗

Endotoxin-induced ascites formation in the rat: partial mediation by platelet-activating factor.

Systemic endotoxemia has been observed in patients with acute and chronic liver failure, and bacterial endotoxin is known to increase vascular permeability. We investigated in the normal rat the effects of intraportal endotoxin administration and the possible mediation of these effects by platelet-activating factor. Injection of endotoxin lipopolysaccharide (10 and 25 mg per kg) in the rat resulted in rapid ascites formation, as well as systemic hypotension, hemoconcentration and acute erosions of the gastrointestinal mucosa. These effects were significantly attenuated by pretreatment with L652,731 and CF-3988, specific platelet-activating factor antagonists. Administration of 25 mg per kg endotoxin also resulted in significant elevations of platelet-activating factor biosynthesis in vitro by samples of duodenum, liver and lung. The effects of endotoxin were mimicked by intraportal infusion of platelet-activating factor (50 ng per kg per min), which induced ascites and gastrointestinal lesions. Platelet-activating factor reduced circulating plasma volume and increased peritoneal permeability to albumin as assessed by the ascites to plasma ratio of labeled albumin. These results, therefore, support a role for platelet-activating factor in mediating endotoxin-induced ascites and gastrointestinal erosions.

Animals↗

Single, total paracentesis for tense ascites: sequential hemodynamic changes and right atrial size.

Hemodynamic changes induced by a single, total paracentesis were evaluated in 21 patients with tense ascites from whom 4 to 16 L of ascites were drained over 2 to 8 hr with no serious complications. At 60 min, compared to baseline, there was an increase in cardiac output (7.7 +/- 0.5 to 8.5 +/- 0.6 L/min, p less than 0.02) and a tendency for right atrial pressure to decrease (9.3 +/- 0.8 to 7.50 +/- 0.8 mm Hg, NS), with no change in pulmonary capillary wedge pressure (10.9 +/- 0.9 to 10.7 +/- 0.9 mm Hg). Between 3 and 12 hr later, there was a drop in right atrial pressure, pulmonary capillary wedge pressure and cardiac output to 5.6 +/- 0.6 (p less than 0.02), 7.2 +/- 0.8 mm Hg (p less than 0.002) and 7.2 +/- 0.6 L/min (NS) respectively, indicative of the development of relative hypovolemia and suggesting that therapeutic plasma expansion is appropriate at this time. Two-dimensional echocardiography before paracentesis (n = 8) showed a reduction in the right to left atrium area ratio as compared with values in patients with minimal ascites (0.54 +/- 0.04 vs 0.82 +/- 0.02, p less than 0.0001). This technique may help in identifying patients with right atrial compression caused by tense ascites.

Adult↗

Treatment of patients with cirrhosis and refractory ascites using LeVeen shunt with titanium tip: comparison with therapeutic paracentesis.

It has recently been suggested that insertion of a titanium tip at the venous end of the LeVeen shunt drastically reduces the rate of shunt obstruction. To assess whether the LeVeen shunt with titanium tip improves the results obtained with therapeutic paracentesis, 81 patients with cirrhosis and refractory ascites were randomly assigned to therapy with paracentesis plus intravenous albumin (42 patients) or LeVeen shunt with titanium tip (39 patients). If patients were readmitted for ascites during follow-up, those in the first group were treated with paracentesis, and those in the LeVeen shunt group by the insertion of a new valve or a new shunt if obstruction was demonstrated. During first hospitalization, both treatments were equally effective in removing ascites. Complications were similar in both groups except for a higher rate of severe bacterial infection in the LeVeen shunt group. The mean duration of hospitalization was shorter in the paracentesis group than in the shunt group. During follow-up, the total number of readmissions and the number of readmissions for ascites were higher in the paracentesis group than in the shunt group (252 vs. 99, P < .001; and 193 vs. 43, P < .001, respectively). The total time in hospital, however, was similar (38 +/- 38 vs. 39 +/- 43 days, P = NS). Three patients had obstruction of the shunt during first hospitalization and 14 patients had a total of 22 obstructions during follow-up. Long-term survival was similar in both groups. The insertion of a titanium tip at the venous end of the LeVeen shunt does not prevent obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.

The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group 1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications.

Angiotensins↗

Management of adult patients with ascites caused by cirrhosis.

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in approximately 90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting.

Ascites↗

Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites.

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.

Administration, Oral↗

Bikunin plus paclitaxel markedly reduces tumor burden and ascites in mouse model of ovarian cancer.

Our previous studies of intraperitoneal ovarian carcinoma in a mouse model demonstrated that bikunin gene transfection could prevent ascites formation and intraperitoneal disseminated metastasis. Although ascites was almost completely inhibited, tumor burden was variably reduced. Several reports have indicated that bikunin may be involved in tumor survival. In the present study, the effectiveness of exogenous bikunin and the biodistribution characteristics of (125)I-bikunin were initially examined in a mouse model of human ovarian cancer HRA cells. The once-daily i.p. administration of bikunin significantly decreased progressive growth of HRA tumors and ascites formation in a dose-dependent manner. Maximal radioisotope tumor uptake peaked at 7.4% injected dose/g at 3 hr. Bikunin binding specificity was demonstrated by reduced tumor uptake after coinjection of excess nonradioactive bikunin. Bikunin was rapidly excreted renally. The bikunin therapy produced the significant inhibition in expression of the proteolysis (uPA and uPAR) and angiogenesis-related molecules (VEGF and bFGF). The second purpose of our study was to optimize the antimetastatic activity of bikunin in combination with paclitaxel against HRA cells growing orthotopically in mice. The once-daily i.p. administration of bikunin (25 microg/g body weight/day) in combination with paclitaxel (i.p., 100 microg/20 g at days 2 and 5) significantly decreased progressive growth of HRA cells in a synergistic fashion. In conclusion, combination therapy with bikunin plus paclitaxel may be an effective way to markedly reduce i.p. tumor growth and ascites in ovarian carcinoma possibly through suppression of uPA, uPAR, VEGF and bFGF expression.

Animals↗

Tumoricidal activity of macrophages isolated from human ascitic and solid ovarian carcinomas: augmentation by interferon, lymphokines and endotoxin.

Peripheral blood monocytes and macrophages from ascitic or solid tumors were obtained from 50 patients with advanced (Stage III or IV) ovarian carcinoma. Blood monocytes and peritoneal macrophages from 76 patients undergoing surgery for benign gynecological diseases were used as controls. Macrophages were 30% (range 0.2-6.2) and 2% (range 0.2-4) of mononuclear cell suspensions from ascitic and solid tumors, respectively. Cytolytic activity was measured as release of [3H]-thymidine from prelabelled mKSARU5 (TU5) target cells at an effector to target cell ratio of 20:1. Peripheral blood monocytes and tumor-associated macrophages had baseline cytotoxicity lower than or similar to that of control peripheral blood and peritoneal macrophages respectively. In vitro exposure to partially purified human fibroblast interferon, lymphokine supernatants or endotoxin augmented the cytotoxicity of mononuclear phagocytes, and no significant difference was observed between control and ovarian cancer effector cells from peritoneal effusions. In four patients, macrophages were isolated from the solid tumor or from the malignant effusion and tested in parallel: in two out of four subjects, macrophages from the solid neoplasm showed defective cytotoxicity compared to ascites effector cells from the same subject. When primary ovarian carcinoma cultures were used as targets, tumor cells from two out of five patients tested were relatively resistant to activated macrophage cytotoxicity. Thus, tumor-associated macrophages from ascitic or solid ovarian neoplasms showed no evidence of activation, in terms of spontaneous cytotoxicity or responsiveness to stimuli: it appears unlikely that small numbers of non-activated macrophages present within primary ovarian carcinomas act as a significant mechanism of restraint of neoplastic growth, at least at this anatomical site.

Ascitic Fluid↗

Altered expression of basement-membrane components and collagenases in ascitic xenografts of OVCAR-3 ovarian cancer cells.

Ascitic ovarian cancer cells, which derive from solid tumors, complicate the treatment of ovarian cancer by spreading throughout the peritoneal cavity. Because basement-membrane components may influence tumor-cell proliferation and dissemination, the present studies examined the production of (a) basement-membrane attachment and migration factors (laminin, fibronectin and type IV collagen); (b) a laminin receptor, the 32/67-kDa laminin-binding protein, the presence of which correlates with malignancy; and (c) metalloproteinases (types I and IV collagenase and stromelysin), by ascitic and cultured OVCAR-3 cells and solid OVCAR-3 tumors. The cultured cells and solid tumors produced high levels of mRNA encoding attachment factors and metalloproteinases, and low levels of mRNA for the 32/67-kDa laminin receptor. In contrast, the ascitic ovarian cells had low or undetectable levels of mRNA encoding laminin, type IV collagen and metalloproteinases, but higher levels of transcripts for the laminin receptor. Our results suggest that the apparent inability of ascitic OVCAR-3 cells to attach to host-tissue surfaces may be a consequence, in part, of low levels of expression of laminin, type IV collagen and/or type IV collagenase.

Animals↗