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Biomedical subjects

S D Costa

Publications and source records attributed to S D Costa.

At least 19 recordsLinked to original sources
PubMed2006

[PTHrP and bone sialoprotein as prognostic markers for developing bone metastases in breast cancer patients].

BACKGROUND: Bone metastases belong to the most frequent metastases in breast cancer. Currently there exist no serum markers which allow early detection of bone metastases. PATIENTS AND METHODS: 89 patients with primary breast cancer have been investigated for parathyroid-hormone-related peptide (PTHrP) in the tumour and bone sialoprotein (BSP) in the serum. Both markers have been correlated with classical prognostic factors and survival. RESULTS: The median age of the patients was 56 years. 17 of the 89 patients developed bone metastases and 25 died during the observation period of 5 years. PTHrP correlated significantly with bone metastases free survival (p = 0.0004) and overall survival (p = 0.0005), whereas BSP correlated only with the bone metastases free survival (p = 0.03). Both markers were shown to be independent prognostic factors for the bone metastases free survival in the multivariate analysis. PTHrP was also found to be an independent prognostic factor for the overall survival. CONCLUSION: The investigation of PTHrP could be a prognostic marker for the presence of bone metastases while BSP could be a marker for the early detection of bone metastases.

Biomarkers, Tumor↗
PubMed2005

[Treatment of breast cancer patients with brain metastases].

Treatment of patients with brain metastases is based on an interdisciplinary approach. It is essential to perform a differenciated indication for procedures with consideration of all therapeutical options like modalities of radiotherapy, surgery and oncology. In the case of multiple brain metastases the whole brain radiotherapy is the standard of treatment, while in case of a single or solitary brain metastasis surgical procedures followed by radiotherapy should be preferred.

Brain Neoplasms↗
PubMed2005

[Suspicion for intraabdominal adhesions -- is open laparoscopy the gold standard?].

Laparoscopy is used for most surgical procedures in gynaecology. In general complications are rare. However, one of the most critical steps is the initial laparoscopic entry into the peritoneal cavity. According to the literature serious complications occur in approximately 1-2/1 000 cases. Whereas major vascular injuries are mainly recognised immediately, delayed recognition of bowel injuries is frequent. Complication rates of different entry procedures used in gynaecological laparoscopy are similar even in high risk patients (intraperitoneal adhesions, obesity). Utilising an open - instead a closed - entry (either by Veress needle or first trocar) technique or alternativ entry positions are suggested by some authors. This review presents data available in the literature and highlights that open laparoscopy is no gold standard.

Abdomen↗
PubMed2005

In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study.

BACKGROUND: Response to the first two cycles of preoperative chemotherapy might differentiate subgroups of breast cancer patients with high or minimal chances for a pathologic complete response (pCR) and may be used as an in vivo chemosensitivity test. METHODS: Breast cancer patients were treated with two cycles of TAC (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2) every 21 days). Patients whose tumors showed a response received four more cycles. Patients whose tumors did not respond were randomized to four additional cycles TAC or NX (vinorelbine 25 mg/m(2) days 1 and 8, capecitabine 2000 mg/m(2) days 1-14, every 21 days). The primary end point was pCR at surgery. RESULTS: Two hundred and eighty-five patients showed a clinical response, in 73.0% after two cycles, in 88.4% at surgery, and a pCR was seen in 17.9%. Breast conservation was possible in 72.2%. Responding patients obtained a pCR in 22.6% whereas non-responding patients reached a pCR in 7.3% and 3.1% with TAC or NX, respectively. Grade III/IV neutropenia and febrile neutropenia were observed during TAC in 70.2% and 13.5%, respectively. Significantly less toxicity were observed with NX. CONCLUSION: Early response to TAC can reliably identify patients with a high chance of achieving a pCR. New effective treatments need to be explored for patients without an early response.

Adult↗
PubMed2004

[Ipsilateral breast tumor recurrence after conservative breast cancer surgery -- diagnosis and therapy].

In spite of the fact that breast cancer is a systemic disease, local control plays an important role in its management. While surgical, radiotherapeutic and systemic therapy of primary breast cancer are performed according to widely accepted guidelines, the management of ipsilateral breast tumor relapse (IBTR) is still a matter of individualised concepts because of the lack of randomised studies. IBTR represents a significant medical problem, since the recurrence rate is 5-15 % after 5 years and 20-25 % after 10 years. Incidence is higher in younger patients, in tumors with an extensive intraductal component, positive tumor margins, axillary lymph node metastases, negative steroid hormone receptors and high proliferative activity. Distant metastases after IBTR occur more often if the interval between primary diagnosis and IBTR is short (e. g. less than 4 years). Diagnosis of IBTR include breast palpation, mammography and breast ultrasound. In addition breast MRI can be used to further differentiate between benign and malignant lesions after breast conservation. Standard therapy in this setting remains mastectomy. Breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Breast irradiation after secondary breast-conservation can be carried out in some cases. Some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. The heterogeneous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients.

Breast Neoplasms↗
PubMed2004

Mitomycin C, 5-fluorouracil and folinic acid (Mi-Fu-Fo) as salvage chemotherapy in breast cancer patients with liver metastases and impaired hepatic function: a phase II study.

Patients with measurable liver metastases due to breast cancer and elevated liver enzymes were enrolled into the study. The planned schedule was mitomycin C 8 mg/m2 on day 1, 5-fluorouracil 750 mg/m2 and folinic acid 300 mg/m2 on day 1 and 2 every 4 weeks (Mi-Fu-Fo). Between May 1998 and December 2002, 30 patients with a median age of 51 years (range 33-74) were enrolled. All of them suffered from extensive metastases of the liver resulting in liver dysfunction. Myelosuppression was the most frequent toxicity. Six patients had a partial remission, 12 patients had stable disease and 12 patients progressed during treatment. The median time to progression was 4.5 months in all patients and 7.0 months in patients who responded to the therapy. The median overall survival for the total population was 6.0 months and in the group of responding patients 12.0 months. Mi-Fu-Fo, therefore, provides a valid option for breast cancer patients with liver dysfunction due to liver metastases.

Adult↗
PubMed2002

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001].

The standard primary therapy of advanced ovarian cancer consists of platinum derivatives in combination with paclitaxel. In a first report presented at this year's meeting of the American Society of Clinical Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in combination with carboplatin, while the toxicity profile present some advantages. The addition of a third drug to platinum-taxane-combination does not appear to improve the therapeutic index. According to the data of the ICON1- and ACTION-trial, carboplatin containing chemotherapies are associated with a significant benefit also in early ovarian cancer. Platinum-resistant disease remains a therapeutic challenge, since the available drugs display only limited activity of short duration. Some experimental data suggest evidence for a possible therapeutic role of small molecules that inhibit the epidermal growth factor receptor (OSI-774) or antisense oligonucleotides interfering with EGF-receptor signalling (ISIS 5132). Novel classes of chemotherapeutic agents, including the acylfulvenes and the epothilone-analogues warrant further study in this disease. Multimodal therapies combining cytotoxic agents with antibodies against CA 12-5 or metalloproteinase inhibitors have failed to demonstrate any survival benefit in patients with ovarian cancer. Despite significant progress in the last decade ovarian cancer remains the most lethal gynaecologic malignancy in women in most western countries. Further multicenter clinical studies are needed to better define new therapeutic options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study.

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size > or = 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m(2), either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.

Adult↗
PubMed2001

Mortality of Colorado potato beetle (Leptinotarsa decemlineata) after sublethal stress with the CryIIIA delta-endotoxin of Bacillus thuringiensis and subsequent exposure to Beauveria bassiana.

Acute or chronic sublethal exposure of Colorado potato beetle larvae to the CryIIIA delta-endotoxin of Bacillus thuringiensis Berliner did not significantly (P > 0.05) alter their subsequent susceptibility to Beauveria bassiana (Balsamo) Vuillemin. During the period of exposure to B. bassiana there was continued mortality from previous exposure to delta-endotoxin, and B. bassiana also caused significant mortality. Acute and chronic exposure to delta-endotoxin significantly prolonged larval development. The weights of prepupae and adults were significantly reduced by exposure to delta-endotoxin, with the greatest effect being from chronic exposure. Separation of the manifestations of stress in time (feeding vs soil stages) and space (toxin damage to the insect gut vs fungal penetration of the cuticle and activity in the hemocoel) may have precluded alteration of insect susceptibility to infection by B. bassiana. Endemic populations of B. bassiana are not expected to influence the development of resistance in the Colorado potato beetle to the delta-endotoxin of B. thuringiensis.

Animals↗
PubMed2001

[Preoperative chemotherapy in primary operable breast cancer with a dose-dense combination of doxorubicin and docetaxel (ADoc) - Experience of the GEPARDO-GABG study group].

OBJECTIVE: The German Adjuvant Breast Cancer Study Group (GABG) conducts trials of preoperative chemotherapy in patients with primary breast cancer using a combination of doxorubicin and docetaxel (ADoc). - PATIENTS AND METHODS: We conducted a parallel-grouped phase IIa-study with 42 patients with a conventionally dosed and a dose-dense ADoc-schedule (4 cycles of Doxorubicin 50 mg/m(2), Docetaxel 75 mg/m(2) i. v. day 1, q day 15 or 22; G-CSF day 3-15 only for the dose-dense schedule) and a randomized phase IIb-study (GEPARDO-Study) with 250 patients with ADoc +/- Tamoxifen. Biological factors were determined immunohistochemically on 197 core biopsies before treatment. A comparison to a sequential AC-Doc regimen including 913 patients has been completed recently. - RESULTS: ADoc can be applicated on schedule in 93 % of all patients. The dose-dense regimen shows a tendency to more toxicity but also to more efficacy. The rate of complete pathological remissions (pCR) was 9.7 %. No difference was found between chemo- and chemoendocrine treatment. Clinically negative lymphnodes and a negative estrogen receptor status is predictive for a higher pCR-rate. To date no differences in toxicity could be found between ADoc and AC-Doc. - CONCLUSIONS: The dose-dense ADoc regimen is well tolerated and highly effective as preoperative therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Interaction of psychosocial and physical risk factors in the causation of mammary cancer, and its prevention through psychological methods of treatment.

Some 8059 healthy women (mean age 58 years) were studied in 1973 with the aim of establishing the presence or absence of a variety of physical and psychological risk factors for mammary cancer. Mortality was established in 1988. factor predictors were highly significant. Physical risk factors were more predictive than psychological ones, but both interacted synergistically to predict mortality. Alone, psychological (stress) factors had little effect, while-physical factors did. However, psychological factors seemed to potentiate the effect of physical factors, particularly in the middle range. The causal relevance of psychological factors was established in a special intervention study using autonomy training as a method of prophylactic therapy and comparing outcome with the effects of no therapy (control).

Adult↗
PubMed2000

Colorado potato beetle (Coleoptera: Chrysomelidae) feeding, development, and survival to adulthood after continuous exposure to Bacillus thuringiensis subsp. tenebrionis-treated potato foliage from the field.

Colorado potato beetle, Leptinotarsa decemlineata (Say), feeding, development, and survival to adulthood were examined after continuously exposing large larvae to Bacillus thuringiensis subsp. tenebrionis-treated potato foliage from the field. In laboratory assays, the overall consumption and the length of period to become prepupae were determined for larvae, which began as 3rd and 4th instars, that were offered potato leaf disks with naturally declining levels of B. thuringiensis residue. In small-cage field experiments, survival to adulthood and the period to adult emergence for beetles confined to potato plants treated with B. thuringiensis beginning as 3rd and 4th instars also were examined. Third instars remaining on plants after a B. thuringiensis application were unlikely to feed and 4th instars consumed only approximately 50% as much foliage as those fed untreated foliage. Many late instars subjected to B. thuringiensis-treated foliage failed to survive to adulthood; 58-83% of these beetles died during the larval stage. Reduced feeding and poor survival of late instars suggest that counts of large larvae after application do not provide a complete picture of the efficacy of the B. thuringiensis treatment. Late instar Colorado potato beetles that were exposed continually to naturally declining levels of B. thuringiensis-treated potato foliage took an average of 1.8-4.5 d longer to become prepupae and 4-8 d longer to emerge as adults compared with those provided with untreated foliage. Delayed emergence of adults that fed on B. thuringiensis-treated potatoes as late instars indicated that development was prolonged in these insects because of ingestion of a sublethal dose of B. thuringiensis.

Animals↗
PubMed2000

Sublethal acute and chronic exposure of Colorado potato beetle (Coleoptera: Chrysomelidae) to the delta-endotoxin of Bacillus thuringiensis.

Sublethal exposure of Colorado potato beetle, Leptinotarsa decemlineata (Say), larvae to the delta-endotoxin of Bacillus thuringiensis variety tenebrionis (Berliner) caused a dose-dependent reduction in feeding and weight gain when tested in a leaf disk bioassay. The highest doses of chronic (continuous-lower concentration) exposure resulted in peak foliage consumption on day 1 as compared with peak consumption on days 3 and 4 when exposure was acute (24-h higher concentration). Dose and exposure regimen interacted significantly in their effects on the extension of development. When development time was analyzed separately for each exposure regimen, only acute exposure caused significant delays in development that extended through to adult eclosion. The efficiency of conversion of ingested material to biomass (ECI) declined significantly with both exposure regimens. The lethal and most sublethal effects of exposure to delta-endotoxin were not cumulative, in that similar total doses, whether delivered acutely or chronically, produced different effects. Female adults that survived acute and chronic exposure to delta-endotoxin as larvae had significantly reduced weight and longevity, and tended to produce fewer eggs (45 and 44% reductions in acute and chronic exposures, respectively) when compared with control adults. The intrinsic rate of increase (r) and net reproductive rate (R0) also appeared to be reduced.

Animals↗
PubMed1999

Maximized reduction of primary breast tumor size using preoperative chemotherapy with doxorubicin and docetaxel.

PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m(2) intravenously [IV] over 15 minutes) and docetaxel (75 mg/m(2) IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1. 8 cm (range, 0 to 4 cm) on sonography (P <.001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.

Adult↗
PubMed1999

The role of docetaxel (Taxotere) in neoadjuvant chemotherapy of breast cancer.

Neoadjuvant chemotherapy has become standard therapy in the management of breast cancer patients with locally advanced disease with inoperable tumors and inflammatory breast cancer. Patients with earlier stage breast cancer and operable tumors may also benefit from treatment with neoadjuvant chemotherapy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is thought to be one of the most potent agents in the treatment of metastatic breast cancer and is therefore being investigated for its likely benefit in preoperative, neoadjuvant regimens. Several large phase II and randomized phase III trials are evaluating docetaxel as a single agent, in combination, and/or sequentially in the preoperative setting. Preliminary findings demonstrate high complete and partial response rates and a tolerable toxicity profile. These results are consistent with the view that incorporation of docetaxel in neoadjuvant chemotherapy regimens will contribute to improved patient outcome. Ongoing studies will provide important information regarding the most appropriate regimens and schedules of docetaxel to use in the preoperative, neoadjuvant setting.

Anthracyclines↗