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S Culine

Publications and source records attributed to S Culine.

125 records · Page 7Linked to original sources

A possible role for the Ras-related Rab2 protein in the immunological events associated with hematological malignancies.

The Rab branch of the Ras-related guanine nucleotide (GTP/GDP)-binding proteins currently includes at least thirty related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. We have demonstrated the overexpression of the Rab2 protein in peripheral blood mononuclear cells from patients exhibiting Sézary syndromes and other lymphoid and myeloid malignancies. Several lines of evidence suggest that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provide strong evidences for the implication of a small GDP/GTP binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

GTP-Binding Proteins↗

Specific expression of the ras-related rab3A gene in human normal and malignant neuroendocrine cells.

BACKGROUND: The authors originally demonstrated the tissue-specific expression of the rab3A gene in the mouse brain. In the current study, they analyze the activity of this gene in fresh human tumors associated with neuronal phenotype compared with normal and malignant cells from other origins. METHODS: The authors studied the transcription levels of the rab3A gene by Northern blot in 81 fresh tumors. RESULTS: A high rab3A gene expression was observed in tumor samples derived from the neural tube (i.e., neuroblastomas, ganglioneuroblastomas, and adult nervous system neoplasms). In addition, this tissue-specific expression extended to neuroendocrine tumors of the gut, small cell lung cancers, and pheochromocytomas. CONCLUSIONS: These results suggest a specific restriction pattern to human cells derived from the neural tube and neural crests. The GTP/GDP-binding rab3A protein may be a useful differentiation marker of neuro-endocrine cells in the characterization of undifferentiated neoplasms.

Biomarkers, Tumor↗

Overexpression of the ras-related rab2 gene product in peripheral blood mononuclear cells from patients with hematological and solid neoplasms.

The rab2 gene product belongs to the rab branch of the ras-related GTP-binding protein family. The rab2 gene mRNA analysis in 70 tumor samples from various origins showed no obvious difference between malignant tissues and their normal counterparts. However, an over-expression has been observed at the RNA or protein levels in peripheral blood mononuclear cells from the nine patients with Sézary syndromes studied. Subsequent investigations in mycosis fungoides and solid tumor patients allowed us to link these high protein levels to immune reactive rather than to malignant cells. Circulating monocyte and lymphocyte populations from cancer patients are under analysis to correlate the Rab2 protein overexpression to a peculiar subset of cells.

Adult↗

[Value of the combination of piperacillin and pefloxacin possibly followed by vancomycin in the treatment of febrile neutropenia in nephrotoxic chemotherapy].

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

Adolescent↗

The human homologue of the putative proto-oncogene Spi-1: characterization and expression in tumors.

Spi-1 is a putative proto-oncogene involved in murine virus-induced acute erythroleukemias. We report here the identification of the human homologue of Spi-1 and its expression in normal and tumorigenic human tissues. Characterization of cDNA clones revealed that the human Spi-1 gene encodes a 216 amino acids protein showing 85% identity with the murine counterpart. By sequencing genomic clones, five exons were identified. To investigate the possible role of Spi-1 gene in human cancers, we studied its expression in a panel of human tumors by Northern blot analysis. Spi-1 expression was detected in all the tumors examined. There was no noticeable evidence of messenger RNA alteration as compared to normal tissues.

Adenocarcinoma↗

[Cancer of the bladder after treatment with cyclophosphamide. Apropos of a case and a review of the literature].

A case of cancer of the bladder is reported in a patient treated 5 years previously with cyclophosphamide for membranoproliferative glomerulonephritis. The responsibility of cyclophosphamide for this type of tumour is well documented in the literature and should lead to a limitation of its use in disease with a favourable prognosis and to close surveillance via regular cystoscopy and blind biopsy in patients who receive more than 50 g of the drug.

Adult↗

Expression of the ras-related rap genes in human tumors.

The expression of the recently described rap genes, closely related in the effector region to the ras proto-oncogenes, was examined by Northern blot analysis in 41 primary human tumors. The structural and in vitro biological properties of the rap gene products suggest their possible antagonistic action in the same effector pathway as the ras proteins. In order to determine whether a deregulation in the rap transcription levels could be involved per se in the multistep carcinogenic process, we chose to analyze tumors for which the ras mutation rate was previously reported to be extremely rare or unknown, i.e., non-Hodgkin's lymphomas, certain types of carcinoma, sarcomas, germinal neoplasms of the testes and various tumors of the nervous system. A severe decrease in the expression of the rap1A gene was shown in the fibrosarcomas and the adenocarcinoma of the salivary gland studied, as compared to their normal counterparts, whereas no rap2 expression was found in the polyadenylated RNA of sarcoma samples.

Blotting, Northern↗

Relationship of histological subtypes to prognosis in early stage Hodgkin's disease: a review of 312 cases in a controlled clinical trial. The Groupe Pierre et Marie Curie.

To assess the prognostic significance of a newer histologic classification of Hodgkin's disease (HD), microscope slides from the time of diagnosis of 312 clinical stage IA or B, IIA or B and IIIA patients were reviewed in 1987, 6-10 years after their participation in a radiochemotherapeutic trial (1976-1982). Overall, the diagnostic reproducibility of the Rye classification by the same pathologist was confirmed. However, a new analysis showed an improvement in the differential diagnosis between HD and non-Hodgkin's lymphomas (NHL) by the identification of 24 NHL (8%) amongst the patients originally diagnosed as HD. Most of the NHL identified on review had been classified originally as mixed cellularity. On review, none of the new histological subtypes of HD was significant for prognosis of relapse-free survival or overall survival. Only identification of NHL was shown to have an independent prognostic value on relapse rate (P = 0.012) and on overall survival (P = 0.10). It is concluded that diagnosis of HD by itself remains, in 1988, the sole histologic factor influencing the prognosis of these patients.

Adolescent↗

[A phase III trial comparing the antiemetic activity of tetracosactide with dexamethasone in combination with metoclopramide, diphenhydramine and clorazepate during chemotherapy including cisplatin].

In order to compare the safety and the antiemetic effectiveness of tetracosactide (TCS) or beta 1,24 ACTH with those of dexamethasone (DXM) as an adjunct to high-dose metoclopramide, diphenhydramine and clorazepate, 33 patients receiving cisplatin based cancer chemotherapy were enrolled in a double-blind cross-over clinical trial. TCS and DXM were given intravenously, respectively at a dose of 2 mg and 20 mg, and concurrently to the cisplatin infusion. No statistically significant difference was noted between the two drugs with regard to efficacy or side effects. We conclude that TCS can serve as a substitute for DXM in combination antiemetic regimens for management of cisplatin-induced nausea and vomiting.

Adult↗

Lymph node interdigitating cell granuloma associated with non-Hodgkin's malignant lymphoma. A case report and review of the literature.

We report a new case of histiocytic proliferation, which histologically resembles histiocytosis X, in a lymph node affected by non-Hodgkin's malignant lymphoma. This brings the total number of such reported cases to 12. Histiocytosis X cells, with folded nuclei, expressed S100 protein and an antigen recognized by anti-CD1 monoclonal antibodies. Ultrastructural study did not show any Birbeck granules and demonstrated a morphology similar to that of interdigitating cells. In the absence of Birbeck granules, the term 'Langerhans' cell granulomatosis' is not correct and should be replaced by either 'interdigitating cell granuloma' according to immunohistochemistry and ultrastructure or 'histiocytosis X-like granuloma' according to optical morphology. The fact that some cells with folded nuclei were positive for lysozyme argues in favor of the existence of transitional cells between histiocytes hnd interdigitating cells. The 11 other reported cases were reviewed. In 6 cases, this type of granuloma was associated with B cell lymphoma. In 3 cases the lymphoma was also probably of B cell type. In 2 cases, no information could be found. We could speculate that these histiocytosis X-like lesions are reactive, resulting from immune disturbances due to the lymphoma and/or the treatment.

Aged↗

[Chemotherapy for urothelial infiltrating tumors].

Since 1985, the gold standard regimen for metastatic tumours of the urothelial tract is a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC protocol). Randomised studies have shown the superiority of the M-VAC regimen over cisplatin alone or in combination with cyclophosphamide and doxorubicin. The limited gain in survival shows that, although chemosensitive, metastatic tumours cannot be cured by the available drug combinations. Amongst new cytotoxic drugs in development, paclitaxel and gemcitabine are likely to be involved in the standard regimen of the future. The studies published to date do not support the routine use of chemotherapy in the neo-adjuvant or adjuvant setting for the management of early stage urothelial tumours.

Antineoplastic Combined Chemotherapy Protocols↗

5-fluorouracil and leucovorin as second-line chemotherapy in carcinomas of unknown primary site.

Carcinomas of unknown primary (CUP) are highly malignant diseases which have poor prognosis. We report in the present study the impact on survival and toxicity of a salvage chemotherapy with 5-Fluorouracil (5-FU) and leucovorin (LV) in 25 patients with CUP who failed first-line treatment with cisplatin-based regimens. Chemotherapy was a bimonthly regimen of intravenous LV 200 mg/m2 as a 2-hour infusion followed by a 1-hour bolus 5-FU 400 mg/m2 and a 22-hour continuous infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. The median number of cycles per patient was 4. Overall toxicity was mild. No objective response was observed. From the start of second-line chemotherapy, the median overall survival was 3 months. The median overall survival from diagnosis was 9 months. Second-line chemotherapy with 5-FU/LV has no impact on survival in patients with CUP.

Adult↗

Pharmacokinetics of high-dose intravenous melphalan in patients undergoing peripheral blood hematopoietic progenitor-cell transplantation.

The pharmacokinetics of melphalan following high-dose (140 mg/m2) i.v. administration were determined in 20 patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation. Melphalan was assayed in plasma by a specific HPLC method with UV detection. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life of 83 minutes (range 52-168 minutes). Estimated peak plasma concentrations ranged from 1.65 to 14.5 micrograms/ml. Plasma levels were lower than the limit of quantitation of the method used (20 ng/ml) 24 hours after drug administration. The average volume of distribution and total clearance were 317 ml/min/m2 (range 127-797 ml/min/m2) and 37.9 l/m2 (range 15.4-108 l/m2), respectively. These parameters are similar to those reported in the literature. A weak correlation was found between total clearance of melphalan and creatinine clearance (p < 0.05). No relationship between the pharmacokinetics of melphalan and myelosuppression and non-hematologic toxicities was recovered. This pharmacokinetic study indicates that on the assumption that there is no more circulating melphalan after seven elimination half-lives, it may be possible to reinfuse autologous PBPC 10-20 hours after melphalan administration.

Adult↗