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Biomedical subjects

S D Costa

Publications and source records attributed to S D Costa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Reduction in new metastases in breast cancer with adjuvant clodronate treatment.

BACKGROUND: Bisphosphonates are effective against the increased bone resorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications. Experiments in animals and preliminary clinical observations indicate that early clodronate therapy reduces the incidence of new bony metastases in breast cancer. We investigated the effects of clodronate on the incidence and extent of new metastases in patients with breast cancer. METHODS: Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 months. All patients in both groups received standard surgical treatment and customary hormonal therapy or chemotherapy. RESULTS: Distant metastases were detected in 21 patients in the clodronate group and in 42 patients in the control group (P<0.001). The incidence of both osseous and visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metastases). Six patients in the clodronate group died, as did 22 in the control group (P=0.001). The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3). CONCLUSIONS: Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who are at high risk for distant metastases.

Adult↗
PubMed1998

[Preoperative chemotherapy of breast carcinoma].

Preoperative chemotherapy represents the standard procedure in inflammatory breast cancer. However, only recently it could be demonstrated that preoperative chemotherapy is beneficial even for patients with operable primary breast cancer. The number of breast conserving surgeries could be increased significantly. Furthermore this in vivo chemosensitivity assay can provide important prognostic as well as predictivy informations. Preoperative chemotherapy is not associated with an increased risk for the patients as outcome is similar to patients with conventional adjuvant treatment. We investigated new regimens to improve this type of chemotherapy and reached a remission rate of 93% with a combination of adriamycin and docetaxel (ADoc). A randomized study (GEPARDO-study) comparing ADoc with ADoc + tamoxifen has recently been started in Germany by the German Adjuvant Breast Cancer Study Group (GABG).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Docetaxel (taxotere) for therapy of breast carcinoma. Highest effectiveness with moderate side effects].

CLINICAL RESULTS: Docetaxel is a taxan which has proven high efficacy in the treatment of breast cancer. The results are consistent throughout all phases of clinical evaluation. High response rates have been observed especially for women after failure of anthracyclins or with liver metastases. Response rates are superior to doxorubicin, while the extent of the side effects is comparable. CONCLUSION: Due to the different toxicity profile a combination of docetaxel and anthracyclins is feasible and has already been demonstrated in early clinical trials. The role of the combinatory treatments in first line or adjuvant setting is currently under investigation.

Antibiotics, Antineoplastic↗
PubMed1996

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.

Adult↗
PubMed1996

[Prognostic significance of p53 autoantibodies in serum of patients with breast carcinoma].

Mutations in the p53 tumor suppressor gene are the most common genetic alterations associated with malignant tumors including breast and gynecologic carcinomas. Overexpression of p53 protein is a result of increased protein stability caused through conformationally alteration. Accumulation of mutant p53 in tumor cells may lead to a humoral immune response with development of p53 autoantibodies. In the present study we investigated the sera of 72 patients undergoing surgery for primary breast cancer and the relation between p53 antibody production, prognostic parameters and clinical outcome. Circulating p53 antibodies were detected in 15 of the 72 examined patients (21%). A correlation to conventional prognostic factors was not observed. Yet the overall survival was worse in patients with p53 antibodies (p < 0.04), suggesting a more aggressive tumor type.

Adult↗
PubMed1995

Identification of neuron-specific ivermectin binding sites in Drosophila melanogaster and Schistocerca americana.

High affinity avermectin binding sites have been identified and partially characterized in membranes from two insect species, Drosophila melanogaster and the locus Schistocerca americana. There is a 10-fold increase in the density of ivermectin binding sites associated with membranes isolated from Drosophila heads (a neuronally enriched tissue source) compared to the bodies (Bmax values were 3.5 and 0.22 pmol/mg, respectively) with only a small difference in the apparent dissociation constant (Kd values of 0.20 and 0.34 nM for heads and bodies, respectively). Membranes prepared from metathoracic ganglia of the locust, Schistocerca americana, were highly enriched in high affinity avermectin binding sites (Kd = 0.2 nM and Bmax = 42 pmol/mg). Using an [125I]arylazido-avermectin analog as a photoaffinity probe, a 45 kDa protein was identified in both the Drosophila head and body tissue preparations. A 45 kDa protein was also specifically labeled with [125I]azido-avermectin in the locust neuronal membranes.

Affinity Labels↗
PubMed1994

Comparison of thumb-counting and comb-counting methods to determine Ctenocephalides felis infestation levels on dogs.

Comb-counting and thumb-counting were compared in a cross-over study to determine which was more accurate for quantifying flea infestation levels on dogs. Twenty beagle dogs were used in the study and infested with either 50 or 100 adult fleas (Ctenocephalides felis). Two groups of five dogs each were infested with either 50 or 100 fleas per dog, and then comb-counted with a fine-toothed flea comb for 8 min periods. An additional two groups of five dogs each were also given 50 or 100 fleas, and then thumb-counted. The counting time for this technique is both lower and more variable because the fleas are only observed and not captured; thus, the speed at which the dog is covered must be increased in order to prevent counting the same fleas more than once. The mean time of thumb-counting per dog was 3.2 min. Fleas removed during comb-counting were placed back on the dog they were taken from after the count was concluded. At the cross-over point, the ten dogs that had been comb-counted were then thumb-counted and the ten dogs that had been thumb-counted were comb-counted. The results showed that comb-counting recovered significantly (P < or = 0.05) more fleas than did thumb-counting. On dogs given 50 and 100 fleas, comb-counting gave mean percentage recoveries of 67.6% and 75.4%, respectively, whereas thumb-counting found means of 8.8% and 7.7%, respectively. The order in which the counting methods were employed produced no significant effect (P > 0.05) on the number of fleas counted.

Animals↗
PubMed1994

[Postoperative management after cesarean section--infusion therapy and role of intestinal stimulation with parasympathomimetic drugs and dexpanthenon].

In the last decade the incidence of cesarean section has raised worldwide to 15-30% of all deliveries. A standardized postoperative protocol can be applied to most cases and it should be easy to handle and at low costs. In the present randomized, prospective study 76 consecutive patients who hat a cesarean section were investigated. Two different infusion therapy protocols were compared and the role of prophylactic stimulation of peristalsis by parasympathometic drugs and by the pantothenic acid derivative dexpanthenon was evaluated. In group A patient (n = 36) were treated postoperatively with intravenous glucose 5% plus electrolytes and received routinely neostigmine and dexpanthenon, while patients in group B (n = 40) were treated with standardized commercially available solutions without intravenous stimulation of the bowel. Both groups were similar in terms of age, parity, gestational age, past medical history and previous abdominal surgery. The volume of urine and the serum electrolyte levels were similar in both groups postoperatively. The first evacuation of the bowel occurred in most cases on day 3 (A = 69.5%, B = 82.5% of the patients). 50% of the patients in group A complained of abdominal discomfort and pain postoperatively and needed some therapy, while in group B only 22.5% of the cases hat similar complaints. This difference was statistically significant (chi 2 Test: p < 0.02). The present data suggest that prophylactic postoperative stimulation of the peristalsis after cesarean section increases the incidence of abdominal discomfort significantly without influencing the bowel function. Standardized solutions can be used mostly for immediate intravenous fluid replacement and oral intake can be started after 2-6 hours.

Adult↗
PubMed1992

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

PURPOSE: At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS: A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

Adult↗
PubMed1991

[Lymphangiosis carcinomatosa of the skin in ovarian cancer simulating scleroderma].

Skin metastases, as the first site of manifestation of ovarian carcinoma, are very uncommon. A report on a case of dermal lymphatic carcinomatosis of the lower part of the body and the breast with the clinical appearance of scleroderma is made. Skin biopsies were performed several times and an invasion of cutaneous lymphatic vessels by carcinoma cells and psammoma bodies due to ovarian cancer was observed, which led to the correct diagnosis of ovarian carcinoma.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

[The prognostic significance of tumor cell detection in bone marrow of patients with breast cancer].

In 95% of patients with primary breast cancer, the extent of metastases cannot be proven by conventional methods. Nevertheless, more than 50% of these patients have a relapse within five years. To improve the predictive value for recurrency, we examined bone marrow aspirates of 128 patients with primary breast cancer. Bone marrow aspirates from 2-6 sites of the skeleton (iliac crest and sternum) were taken as well as biopsies for histological examination. The immunohistochemical studies were carried out on interphase smears and stained with cytoceratin antibodies (PKK 1) and antibodies against tumor-specific antigen TAG 12 (12 H 12). All patients were screened for distant metastases (X-ray, ultrasound, bone scan). Tumor cells and micrometastases in bone marrow were detected in 41 patients (32%). Their presence was correlated to other prognostic factors (tumor size, lymph node status, oestrogen/progesterone receptors). The median duration of follow-up was 39.5 months. 14 patients (45%) in the tumor cell positive group relapsed, compared to only 4 out of 36 patients in the tumor cell negative group. In 29% we found bone metastases. The relapse free interval was shorter for patients with micrometastases (8 vs. 15.8 months). The presence of tumor cells in bone marrow aspirates detected at the time of primary surgery, is a useful prognostic factor and a good predictor of metastases and may help in selecting patients for systemic adjuvant treatment.

Antibodies, Monoclonal↗
PubMed1990

The relationship between size and parity status of field collected Culiseta melanura.

The relationship between body size and parity status of adult female Culiseta melanura collected from 3 locations in northeastern United States was studied by measuring wing lengths and examining ovaries of individual mosquitoes. Virus isolation was attempted from Cs. melanura collected in Maryland and in New Jersey. At all 3 locations, the size of Cs. melanura collected varied from large in the spring, to small in the summer. In New Jersey and Maryland mosquitoes collected in the fall were again large. The size of Massachusetts mosquitoes collected in the summer versus the fall was not different. In general, parous mosquitoes were larger than nulliparous mosquitoes in the spring but smaller than nulliparous ones in the fall. Eastern equine encephalomyelitis (EEE) and Highlands J (HJ) viruses were recovered from Cs. melanura only during the late summer when mosquitoes were small or during the fall months when larger mosquitoes were collected. We conclude that there is no detectable association between Cs. melanura size and parity status and that there is no obvious effect of mosquito size on EEE or HJ virus transmission.

Animals↗
PubMed1989

[Epithelial growth factor receptors (EGF-R) and DNA flow cytometry in addition to lymph node and hormone receptor status as prognostic factors in primary breast cancer].

The presence of receptors for epidermal growth factor (EGF-R), the percentage of cells in S-phase and DNA-ploidy measured by flow-cytometry are new prognostic factors in breast cancer. In order to investigate the relationship between EGF-R, S-Phase/DNA-ploidy and clinical data, we measured these parameters in 68 tumors from patients with operable breast cancer. 11 Patients had positive EGF-R's (specific binding greater than 10 fmol/mg membrane-protein) and 37 patients had a positive S-Phase (more than 5% of cells in S-Phase). 10 of 44 carcinomas of ductal type were EGF-R positive, while only 1 of 18 lobular-type tumor displayed positive EGF-R's. We found significant inverse correlations between EGF-R's and estrogen receptors (p less than 0.00001) and between EGF-R's and age (p less than 0.0001): EGF-R positive tumors were found more often in young patients and in patients with estrogen-receptor-negative tumors. The EGF-R's and flow-cytometric data did not correlate with tumor size and/or nodal status. There was no correlation between EGF-R and S-Phase/DNA-ploidy in the breast cancer specimens suggesting that these two prognostic parameters are independent from each other.

Biopsy↗
PubMed1986

Effects of tumor promoters on growth and on cellular redistribution of phospholipid/Ca2+-dependent protein kinase in human breast cancer cells.

Active, structurally unrelated tumor promoters (12-0-tetradecanoyl-phorbol-13-acetate (TPA), teleocidin and aplysiatoxin) inhibit growth of mammary carcinoma cells (MCF7- greater than BT-20 greater than MDA-MB-231 greater than = ZR-75-1 greater than HBL-100). This efficiency in inhibiting cell growth correlates with the tumor-promoting activity of a series of phorbol ester derivatives. The phospholipid/calcium-dependent protein kinase (PKC), a target for phorbol ester action, was measured by polyacrylamide gel electrophoresis. The levels of PKC were higher (p less than 0.001) in estrogen-receptor-negative than in estrogen-receptor-positive cells. Treatment of cells with active tumor promoters results in time- and dose-dependent translocation of cytosolic PKC to membrane fractions. Less potent phorbol esters induce only partial translocation of PKC (i.e., decrease of cytosolic without increase in membrane-bound PKC), whereas inactive esters have no effect. No correlation was found between PKC concentration or the amount of PKC translocated to membranes and the sensitivity of the respective cells to TPA. It is concluded that tumor-promoter-mediated growth inhibition of breast cancer cell lines is due to mechanism(s) occurring after the translocation of PKC.

Breast Neoplasms↗