BACKGROUND: The chronomodulated infusion of 5-FU, FA and oxaliplatin allows a significant increase in dose intensity and antitumor efficacy in patients with metastatic colorectal cancer. Here we investigated if substitution of oxaliplatin with cisplatin produced a similar antitumor activity in previously untreated patients with advanced colorectal cancer. METHODS: We enrolled 21 consecutively evaluated ambulatory patients with metastatic colorectal cancer. Each treatment cycle consisted of a 5-day course of continuous chronomodulated venous infusion of drugs. Daily doses were 600 mg/m2 5-FU, 150 mg/m2 FA (L-form), and 12 mg/m2 cisplatin. The cycles were repeated every 21 days. RESULTS: All patients completed at least 3 cycles. Overall a total number of 105 cycles were administered. One partial response (lasting 3 months) and 13 stable disease (lasting from 3 to 12 months) were observed. The remaining 7 patients had progression of the disease. Hematologic and gastrointestinal toxicity was always < or = G2 in all cycles. CONCLUSIONS: The results of this study discourage the substitution of cisplatin for the more active compound, oxaliplatin, in a chronomodulated schedule of infusion with 5-FU and FA in patients with metastatic colorectal cancer.

Adult↗

PubMedDate not supplied

Peritoneal mesothelial cells as a significant source of ascitic immunostimulatory protein 90K.

The tumor associated antigen 90K is known to possess cytokine-like modulatory properties on the cellular immune system, whereby accessory cells are the primary target of this molecule. In 67 ovarian cancer patients presenting with significant amounts of ascites, immunostimulatory protein 90K was detected in all ascitic fluid samples examined. Furthermore, 90K levels correlated to ascitic s-IL-2R content. To elucidate the source of protein 90K in ascitic fluid; its in vitro release was investigated in primary cultured normal human peritoneal mesothelial cells (HPMC). Peritoneal mesothelium was found to produce five-fold more 90K than ovarian cancer cells. Release of protein 90K was significantly increased by treatment with IFN-gamma in both mesothelial and ovarian cancer cells. In contrast neither IL-1 beta nor TNF-alpha treatment consistently influenced the secretion of 90K in either cell type.

Adult↗

PubMedDate not supplied

Longitudinal analysis of the 90K glycoprotein in the Italian HIV-seroconversion study: temporal trend and predictability of the maturity of HIV infection.

OBJECTIVES: To evaluate the level of 90K as a predictor of AIDS; to describe 90K levels over time after HIV serconversion; and to evaluate the 90K level as a marker of the maturity of infection. DESIGN: Prospective incident cohort of HIV-infected individuals with documented dates of seroconversion. METHODS: Cox models were applied to estimate the crude and adjusted relative hazards (RH) of AIDS by level of 90K. Regression models were applied to describe the temporal trend and the correlates of the level of 90K over time after HIV-seroconversion. Logistic models were applied to evaluate the probability of a sample of 90K having been taken within a certain time period after HIV-seroconversion. RESULTS: The study population consisted of 150 participants of the Italian Seroconversion Study. A total of 429 measurements of 90K were taken. Both early and later measurements of 90K were highly predictive of AIDS, also when adjusting for CD4 lymphocyte count and HIV load. The 90K level (U/ml) increased by 10% annually (95% CI: 7%-13%); the increase over time was linear. IDUs had higher 90K levels than heterosexuals and homosexuals over the course of HIV disease. High 90K levels were highly predictive of distant seroconversions (age-adjusted probability, 74%), whereas were poorly predictive of recent seroconversions (age-adjusted probability, 5%); the results were similar for the predictability of CD4 lymphocyte count. CONCLUSIONS: The level of 90K is a useful prognostic tool for clinical purposes. As a marker of the maturity of infection, 90K is similar to the CD4 lymphocyte count, with the advantage of being able to use serum instead of fresh whole blood. It has a good capacity to identify distant infections.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Hairy cell leukemia: prognosis and treatment].

AIMS: To analyze clinical and laboratory features at presentation in correlation to treatment response and overall survival; evaluation of different treatment approaches. METHODS: The data of 151 consecutive HCL patients observed between 1982 and 2005 were retrospectively analyzed. RESULTS: The following data at presentation were analyzed and compared to response, DFS, PFS and OS: Hb < 10 g/dl (observed in 27% of patients); Plt < 100,000/microl (72%); WBC > 10,000/microl (15%); Splenomegaly (75%); Bone marrow involvement > 70% (27%). At univariate analysis only WBC > 10,000/microl resulted significantly correlated to reduced PFS. 88 Pts received as first line treatment alpha2-interferon (IFN) alone, 49 purine analogues (PA) alone or in combination with IFN, 5 were treated with splenectomy. Among IFN treated patients CR, PR and SD were obtained in 21.6%, 73.8%, 4.5% respectively of the patients; while among PA treated patients in: 26.5%, 71.4%, 2.0% respectively. DFS was significantly prolonged in patients treated with PA with respect to IFN. No significant difference in OS was observed. Median PFS was 27.6 months, median OS is projected at 238 months after a median follow up of 131 months. CONCLUSIONS: Among the routine clinical and hematochemical baseline features only the presence of WBC > 10,000/microl was correlated to a lower PFS. First line treatment with purine analogues is correlated to prolonged PFS and DFS with respect to IFN; nevertheless no difference is observed in OS.

Adult↗

PubMedDate not supplied

Advanced breast cancer: response to somatostatin.

It has previously been reported that a somatostatin analogue has a direct antiproliferative effect on human breast cancer cells in vitro. Here we report preliminary data on the effects of the in vivo administration of SMS in patients with advanced breast cancer. The regimen consisted of iv infusion of 750 micrograms SMS t.i.d. for 10 days followed by 5 days at 500 micrograms im b.i.d. A partial response was observed in 3 out of 10 patients treated. Moreover, a marked reduction of oedema, cyanosis and bleeding from ulcerated tumor lesions was noted in most of the treated patients. Administration of SMS was devoid of toxic side effects. It is suggested that SMS may be of potential value in the therapeutic approach to advanced breast cancer.

Breast Neoplasms↗

PubMedDate not supplied

Bone marrow micrometastases detected by a monoclonal antibody in patients with breast cancer.

One major problem in primary breast cancer is the identification of new parameters able to select patients at high risk of recurrence. Our study was aimed at detecting mammary tumor cells in the bone marrow of breast cancer patients using a single bone marrow sampling and the monoclonal antibody AB/3. This antibody recognizes a membrane carbohydrate epitope present in human breast cancer cells but not in normal tissues. Only 2 out of 45 breast cancer patients were found to have a bone marrow positive AB/3 staining reaction. Our data confirm and extend previous reports that single bone marrow sampling coupled with immunocytochemistry is not sensitive enough to be used as a routine procedure to acquire prognostic information in breast cancer.

Antibodies, Monoclonal↗

PubMedDate not supplied

An antiestrogenic action of interferons in human breast cancer cells.

The antiproliferative and antiestrogenic effects of human interferon on estrogen-dependent CG-5 human breast cancer cells in vitro are reported. Fibroblast beta - interferon as well as recombinant alpha - and gamma -interferon inhibited proliferation of CG-5 cells in a dose and time - dependent fashion. In addition, they completely suppressed the two-fold increase in cell number induced by estradiol and showed an additive antiproliferative effect when used in combination with the antiestrogen tamoxifen. These antiestrogenic effects of interferons were accompanied by a reduced receptor binding of estradiol to the cells.

Breast Neoplasms↗

PubMedDate not supplied

Growth inhibitory effect of LH-RH analogs on human breast cancer cells.

The antiproliferative effect of two LH-RH agonists (Pro 9-LH-RH ethylamide and D Ser(t BU)6 Aza Gly 10-LH-RH, ICI 118630) on the human breast cancer cell line CG5 is reported. Although ineffective when used alone, both analogs inhibited in a dose-dependent fashion the growth stimulatory effect of estradiol. LH-RH analogs did not influence the growth inhibitory effect of tamoxifen and medroxyprogesterone acetate. Likewise, these compounds neither modified basal estrogen and progesterone receptor levels nor prevented estrogen-induced increase of progesterone receptor. A marked antiproliferative effect of the analogs was also seen in cells stimulated with other mitogens, such as insulin and epidermal growth factor.

Breast Neoplasms↗

PubMedDate not supplied

Measurement of a monoclonal-antibody-defined antigen (90K) in the sera of patients with ovarian cancer.

Serum levels of CA125 and 90K, a new tumor-associated antigen, were measured in 73 ovarian cancer patients and 70 patients with benign gynecological conditions. Abnormally high serum CA 125 and 90K levels were found in 49% and 78% of these patients, respectively. When a combination of the two markers was used, the sensitivity increased to 86%. The percentage of 90K positivity did not significantly correlate with stage of disease or with histological type. A statistically significant correlation was found between 90K positivity rate and grade of tumor differentiation. Elevated serum CA 125 and 90K levels were present in 32% and 29% of patients with benign ovarian tumors, respectively. Only 1 case out of 26 with endometriosis had high 90K levels, compared to 7 patients with abnormal CA 125 levels. Serial measurements of 90K concentrations were found to be correlated with the clinical behaviour of the disease during chemotherapy. Moreover, rising levels of 90K preceded the clinical detection of recurrence with a median lead-time of 3 months. In 2 of these cases the serial changes in 90K values were better correlated with the course of disease than changes in CA 125 levels. Our data suggest that 90K combined with CA 125 may be applied for the detection and monitoring of ovarian cancer.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Attempts to characterize dexamethasone receptors present in rat kidney cytosol].

Density gradient centrifugation analysis has been used to study rat kidney receptors for dexamethasone. Density gradients performed with cytosol incubated with 3H-dexamethasone in a Tris 10 mM, EDTA 1.5 mM, glycerol 5%, monothioglycerol 12 mM (pH 7.5) buffer never gave any good evidence of a 85 radioactivity peak probably due to instability of the complex. The stability of the complex for at least 30 h was achieved by homogenizing the tissue and incubating cytosol in a distilled water, glycerol 5% monothioglycerol 12 mM solution. Density gradient centrifugation analysis in this way showed radioactivity peak at the bottom of the tube probably due to the aggregation of the complex. Since this drawback is inherent in the technique it must be concluded that density gradient centrifugation analysis cannot be used to study the dexamethasone-receptor complex of the kidney.

Animals↗

PubMedDate not supplied

[Cervix mucus. I. Physico-chemical characteristics].

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Amino Acids↗

PubMedDate not supplied

[Cervix mucus. II. Quantitative changes--spontaneous or induced by hormonal treatment].

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Cervix Mucus↗