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Biomedical subjects

G Zalcman

Publications and source records attributed to G Zalcman.

At least 19 recordsLinked to original sources
PubMed2004

Randomised, multicentre phase II study assessing two doses of docetaxel (75 or 100 mg/m2) as second-line monotherapy for non-small-cell lung cancer.

BACKGROUND: The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy. Docetaxel (Taxotere) has proven efficacy in both settings. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy. PATIENTS AND METHODS: In total, 182 patients from 24 French centres were randomised and treated with either docetaxel 75 mg/m(2) (arm A) or 100 mg/m(2) (arm B) every 3 weeks. Baseline characteristics were well balanced, except more patients in arm A had metastatic disease (91.4% versus 78.7%) and therefore the median number of sites involved for arm A was three compared with two for arm B. RESULTS: Median time to treatment failure was 1.34 months [95% confidence interval (CI) 1.28-1.64] for arm A and 1.64 months (95% CI 1.34-2.62) for arm B. Median overall survival was 4.7 months (95% CI 3.8-5.9) for arm A versus 6.7 months (95% CI 4.8-7.1) for arm B. According to a blinded expert panel, disease control was achieved in 35 (43.8%) patients in arm A and 39 (49.4%) patients in arm B. More patients in arm B experienced grade 3-4 neutropenia (B: 72.7% versus A: 44.0%), asthenia (B: 20.2% versus A: 10.8%) and infection (B: 6.7% versus A: 2.2%). Three treatment-related deaths were reported in each arm. CONCLUSIONS: The optimal docetaxel dosage in this second-line setting is 75 mg/m(2), as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m(2) dose.

Adult↗
PubMed2003

Splice mutations in the p53 gene: case report and review of the literature.

Splice mutations in the p53 gene (TP53) are described as rare events that occur at a frequency of less than 1%. Using a functional assay based on the transcriptional activity of p53 and using RNA as starting material, we describe here a p53 splice mutation that could not be detected by genomic sequencing. This lack of detection is due to a deletion of the region complementary to primers commonly used for amplification. Reviewing the literature, we show that p53 splice mutations have been certainly underestimated and that careful strategy should be used for a complete mutational analysis of the p53 gene. Furthermore, some p53 gene mutations described as "neutral" due to the absence of any amino-acid change are truly deleterious, as they affect gene splicing.

Alternative Splicing↗
PubMed2001

Detection of p73 antibodies in patients with various types of cancer: immunological characterization.

p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino- and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells.

Antibodies, Neoplasm↗
PubMed2000

Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family.

Grb7 is a member of a family of molecular adapters which are able to contribute positively but also negatively to signal transduction and whose precise roles remain obscure. Rnd1 is a member of the Rho family, but, as opposed to usual GTPases, it is constitutively bound to GTP. We show here that Rnd1 and Grb7 interact, in two-hybrid assays, in vitro, and in pull-down experiments performed with SK-BR3, a breast cancer cell line that overexpresses Grb7. This interaction involves switch II loop of Rnd1, a region crucial for guanine nucleotide exchange in all GTPases, and a Grb7 SH2 domain, a region crucial for Grb7 interaction with several activated receptors. The contribution of the interaction between Rnd1 and Grb7 to their respective functions and properties is discussed.

Antibodies↗
PubMed2000

Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer.

p53 tumour suppressor gene alterations are one of the most frequent genetic events in lung cancer. A subset of patients with p53 mutation and cancer exhibited circulating serum anti-p53 self-antibodies (p53-Ab). The prevalence of these antibodies in lung cancer is currently being analysed in a multicentric study. In a group of homogeneous SCLC patients, p53-Ab were detected in 20/97 (20.6%) individuals. In this group of patients, Cox's multivariate analysis identified disease extent (p = 0.022), WHO initial performance status greater than 0 (p = 0.005), and the absence of a complete response after 6 months of treatment (p < 0.0001) as independent prognostic variables, with p53-Ab being of borderline significance (p = 0.051). In the subset of limited-stage SCLC patients, Cox's multivariate analysis found p53-Ab (p = 0.033), WHO initial performance status greater than 0 (p = 0.028), and absence of a complete response (p < 0.001) to be independent prognostic variables. Thus, actuarial analysis showed that patients with limited-stage SCLC and p53-Ab had a median survival time of 10 months, whereas limited-stage SCLC patients without p53-Ab had a 17-month median survival time (p = 0.014).Therefore, serum assay of p53-Ab could help to identify a population of SCLC patients with an especially poor prognosis. This population could represent patients with tumours harboring aggressive p53 mutations.

Biomarkers↗
PubMed1999

Quantitative fluorescence in situ hybridization in lung cancer as a diagnostic marker.

The diagnosis of lung cancer is quite often hampered by the existence of various cell types within samples such as biopsies or pleural effusions. We have established a new marker for image cytometry of interphase tumor cells of the lung by using the most recurrent and early cytogenetic event in lung cancer, the loss of the short arm of chromosome 3. The method is based on the detection of the imbalance between the long and the short arms of chromosome 3 by performing two-color fluorescence in situ hybridization on both arms. Fourteen tumors were analyzed after short-term culture and compared with the corresponding cytogenetic data obtained from metaphase analysis. Results on interphase nuclei and control experiments on metaphases were the same, with imbalance ratios ranging from 1.0 to 2.0 (mean value 1.6, median 1.5). To assess the clinical significance of this approach, three pleural effusions were analyzed. Data showed that normal cells within the sample could have been distinguished from the tumor cells based on different imbalance values between the long and the short arms. Thus, our method allows refined detection of lung tumor cells within samples containing heterogeneous cell populations.

Biomarkers, Tumor↗
PubMed1999

[Peritoneal fistulization in pleural aspergillosis associated with skin lesions].

This report describes the development of a pleuroperitoneal fistula complicating pleural aspergillosis in a 63-year old non-immunocompromised man treated with itraconazole. The patient presented a confluent granuloma of the abdomen while an abscess of the abdominal wall was disclosed. Skin involvement, usually described in disseminated aspergillosis, has not been reported in pleuropulmonary aspergillosis.

Abdominal Muscles↗
PubMed1998

Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.

Antibody Formation↗
PubMed1997

[Concomitant radiochemotherapy in inoperable non-small cell lung cancer].

PURPOSE: As locally advanced and inoperable non-small cell lung cancers still have a poor prognosis, the present phase II study focused on the administration of concomitant chemotherapy and radiotherapy and was aimed at increasing both local and metastatic controls. MATERIALS AND METHODS: Thirty-nine patients (36 male and three female patients, mean age, 56 years) were included into the study. Ninety five percent of them had a good performance status (OMS status 0 or 1). The histopathological analysis showed the existence of squamous cell in 64% of the cases. There was one stage I tumor, nine stage IIIA tumors and 24 stage IIIB tumors. In two cases, the tumor stage was unknown. The duration of each cycle of the protocol was 3 weeks and included the administration of cisplatin (50 mg/m2 at d1 and d2) and fluorouracil (5-FU) (1 gr/m2 in continuous infusion at d1, d2, and d3), and external beam irradiation (20 Gy subdivided into 2 Gy-fractions that were administered from d1 to d12); the 3rd week was a resting period. RESULTS: The tolerance to the treatment was good. Fifteen per cent grade 3-4 leucopenia, 3% grade 3-4 thrombopenia and 15% grade 3-4 nausea with vomiting were observed. No serious esophagitis was recorded. Chemotherapy was completed in more than 90% of the cycles. An objective response was described in 56% of the cases, with only 3% of complete responses. However, evaluation was done on average 6 weeks after radiotherapy, at a time where post-irradiation fibrosis could hamper radiological assessment. Median survival and 2- and 3-year survivals were 11.4 months, 27% and 14%, respectively. The only significant prognostic factor was the OMS performance status index, while the radiological response was particularly non-predictive of survival. Failure patterns were analyzed in 20 patients and consisted of the following: local relapse only, six cases; metastatic relapse only, 13 cases; both local and metastatic relapse, one case. CONCLUSION: The concomitant administration of 5-FU, cisplatin and external irradiation seems feasible in current clinical practice. Survival but not radiological response should be the only criteria to evaluate this type of association. Improvement in local control is not unlikely with this type of association.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Endobronchial brachytherapy: the Saint-Louis Hospital experience].

PURPOSE: During the evolution of lung cancer, bronchial obstruction is often noticed and is sometimes responsible for serious symptoms. Several methods of desobstruction can be proposed, including brachytherapy. MATERIALS AND METHODS: One hundred forty-nine patients presenting with endobronchial brachytherapy were included into the study. Seventy-three were treated with curative intent, 47 with palliative intent and 29 with a combination of external irradiation and brachytherapy. We usually delivered a series of two 7-Gy fractions (1 cm from the catheter), the treatment being repeated one, two or three times. RESULTS: When all symptoms were taken into account, respiratory function improvement was present in 79% of the patients. Among the 132 tumors that could be evaluated via a new endoscopy 2 months after treatment, 64 (48.5%) were in complete histological remission. The median survival was 14.4 months for the patients treated with curative intent. Eleven massive hemoptysies and 13 radiation bronchitis were observed. CONCLUSION: These results confirm the feasibility and good results related to endobronchial brachytherapy, though controlled studies are needed to better define its place in the therapeutic strategy of bronchial carcinomas.

Aged↗