1061. [Roles of the pathologist in neoadjuvant chemotherapy: evaluation of response, prognostic and predictive factors].
Induction chemotherapy is a therapeutic option for women presenting with invasive tumors over 3cm. This management is aimed to reduced tumor size in order to avoid mammectomy and to test the in vivo chemo sensitivity of the tumor cells. The pathologist plays a key role in optimal management of patients enrolled in induction chemotherapy trials. Evaluation of pretreatment biopsies contributes to establishment of key management parameters such as tumor type, SBR grade immunohistochemical parameters. This evaluation gives predictive parameters of drug response such as hormonal status, proliferation rate, HER2. The evaluation of the post treatment tumor residue helps in determinating tumor response to treatment, establishing prognosis and adjusting adjuvant regimens. Standard histopathological procedures are mandatory.
1062. [Effect of Macrovipera lebetina and Cerastes cerastes venoms on adherence to integrins of cancerous cells (IGR39, HT29-D4 and IGROV1)].
作者: N Marrakchi.;S Sarray.;J Marvaldi.;M El Ayeb.;J Luis.
来源: Arch Inst Pasteur Tunis. 2002年79卷1-4期3-9页
In this work, we provide experimental arguments in favor of the fact that components from Macrovipera lebetina and Cerastes cerastes venoms bind to IGR39 melanoma cells but not to HT29D4 cells that derive from carcinoma adenome. Furthermore, Macrovipera lebetina and Cerastes cerastes venoms inhibit the adherence of IGR39 and HT 29-D4 to various extracellular matrix proteins. Macrovipera lebetina and Cerastes cerastes venoms did not inhibit the non specific adherence of IGR 39 cells to polylysine. In addition, binding of components from Cerastes cerastes venom to IGR39 cells is inhibited by GRGDS peptide and by monoclonal antibidy anti-av, while these two components have no effect on the adherence of IGR39 to Macrovipera lebetina venom.
1063. [Involvement of matrix metalloproteinases (MMPs) in cutaneous melanoma progression].
Among skin cancers, melanoma is probably the most highly invasive and metastasizing, with a poor outcome. During melanoma progression, tumor cells must across the dermal-epidermal junction, and invade the dermis, its principal site of propagation. Therefore, degradation of matrix proteins constituting dermal-epidermal junction and dermis by proteolytic enzymes is an essential step of melanoma invasion. Serines proteinases and Matrix Metalloproteinases (MMPs) families are the main degrading substances involved in this process. Among MMPs, the expression of MMP-1, -2, -3, -9, -14, 15, -16 by melanoma cells was shown in vitro and in vivo, and correlated with the invasive phenotype. In addition to disrupt matrix proteins, MMPs can also cleave non matrix components such as cytokines, and growth factors. The modifications generated by the remodeling of matrix and non-matrix components can influence melanoma cells proliferation, adhesion, vascularization, survival, proteases expression, and migration. Thus, using inhibitors in order to control expression, activation and activity of MMPs could regulate cellular process which led to melanoma progression.
1065. [Saccharomyces cerevisiae: an efficient tool and model system for anticancer research].
作者: Jean-Emmanuel Kurtz.;Patrick Dufour.;Brigitte Duclos.;Jean-Pierre Bergerat.;Françoise Exinger.
来源: Bull Cancer. 2004年91卷2期133-9页
The major mechanisms of cell function, such as metabolic pathways, DNA repair and cell cycle control have been conserved throughout DNA evolution from yeast to human, despite the former lacks cancer-related features. The S. cerevisiae genome has been entirely sequenced and not only reveals sequence similarity to the human, but a number of proteins also have a conserved function. Owing to its genetic features, yeast has been used as a remarkable model and tool to study important enzymes that are also targets for anticancer drugs, particularly in the field of the pyrimidine salvage pathway. In this review, we describe the recent developments in using yeast for anticancer research, focusing on metabolic pathway analysis, systematic drugs screening with yeast mutants or prospects in gene therapy with yeast enzymes.
1067. [Sarcoidosis granuloma on a tattoo induced by interferon alpha].
The side effects attributed to interferon alpha are numerous, including autoimmune events such as lupus, arthritis or thyroiditis. Emergence of sarcoidosis in patients with interferon alpha therapy is much more rare. We describe a case occurring in a patient treated for melanoma.
1068. [Palpebral edema secondary to treatment by a specific inhibitor of tyrosine kinase: Glivec. A case report].
作者: T Maalouf.;K Angioï.;J Champigneulle.;A Guerci.;J-L George.
来源: J Fr Ophtalmol. 2004年27卷1期107-9页
Iatrogenic causes for palpebral edema are rarely suspected and must be specifically sought. The authors report a case of palpebral edema in a patient treated with a specific inhibitor of the BCR-ABL tyrosine kinase (Glivec) for chronic myeloid leukemia. Histopathological analysis of specimens of the excised upper eyelid tissue revealed the absence of leukemic infiltration, suggesting the toxic effect of the treatment. This side effect should be noted so that patients are informed and biopsy is proposed to eliminate tumoral infiltration.
1069. [Cancer and pregnancy: risks of exposure to cancer chemotherapy during pregnancy].
Animal studies reveal that almost all antineoplastic agents are teratogenic. But extrapolation to human beings is not simple because of species differences. Few human data are available, most are sporadic case reports. Other toxic effects for the fetus and neonate (intrauterine exposure during second and third trimester) must be taken in consideration when prescribing chemotherapy for pregnant women. Adverse effects observed in adult and children are helpful if data during fetal life are lacking. Long-term studies are needed to evaluate the transplacental effects of chemotherapy during pregnancy; these studies should assess the child's mental and physical development, infertility and the occurrence of second malignancies.
1070. [Cancer and pregnancy: the medical oncologist's point of view].
Having to start chemotherapy during pregnancy remains a rare event. The decision to proceed with this treatment depends on the drugs used, the time of exposure for the fetus and the gestational age at the time of exposure. The mutagenic potential of the chosen drug has to be known. The risk for the child can then be established without compromising the mother's chances of survival or well-being. This type of situation generally arises in women with breast cancer, leukemia or lymphoma. The first trimester of pregnancy, which corresponds to organogenesis is the most critical period for the fetus. The greatest risk of malformation occurs with anti-metabolite drugs. Chemotherapy can also expose the child to direct in utero toxicity. Myelosuppression is the most common toxic effect, sometimes giving rise to infections and/or fetal hemorrhage. The long-term risks of cancer on the mother's subsequent fertility or the child's intellectual development are not well-known. Such factors must be examined in prospective studies and registered in a specific database.
1071. [Fatal fulminating hepatitis induced by nilutamide].
作者: André Edouard.;Roselyne Robinel.;Christel Rat.;Frédéric Lombard.;Catherine Lorinet.;Patrick Escarmant.
来源: Gastroenterol Clin Biol. 2003年27卷12期1170-1页 1072. [Liposomal doxorubicin and palmoplantar erythrodysesthesia].1073. [Focus on cellular pharmacology of docetaxel].
Docetaxel, a member of the taxoid class of antineoplasic agents, is derived from an inactive precursor obtained from the needles of the European yew. Docetaxel is characterised by a wide spectrum of in vitro cytotoxicity an murine and human tumour cell lines and in vivo antitumour activity against human tumour xenografted in athymic mice. The principal mechanism by which docetaxel exerts its cytotoxic activity is through enhancement and stabilisation of microtubule assembly leading to an arrest of the cell cycle at the G2/M phase. It has also been shown to induce tumour cell death by apoptosis and to have antiangiogenic and immunostimulating properties. Docetaxel demonstrated in vitro and/or in vivo additive and synergistic effects when combined with a large spectrum of anticancer therapies such as new cytotoxic agents (gemcitabine, capecitabine, edatrexate), specific signal transduction drugs, Herceptin, antiangiogenic drugs, gene therapy, or antisense olignonucleotides, opening to new treatment strategies. Despite close chemical structures, preclinical data suggested a difference in the cellular pharmacology of docetaxel and paclitaxel leading to different profiles in clinical studies.
1074. ["Spontaneous" resolution of two severe methotrexate-induced pneumonias].
作者: K Berkani.;J-Y Bayle.;M Perol.;F Bejui-Thivolet.;D Perrot.;J-C Guerin.
来源: Rev Pneumol Clin. 2003年59卷5 Pt 1期301-5页
The beneficial role of corticosteroid therapy for the treatment of methotrexate-induced pneumonia remains controversial. We report two cases of acute severe interstitial pneumonia induced by methotrexate in patients with non-Hodgkin lymphoma given a polychemotherapy protocol (M'BACOD). The first signs appeared on the eleventh day of the first cycle in patient one and on the tenth day of the third cycle in patient two. The causal implication of methotrexate was based on the history, the clinical and radiological presentation, and the negative tests in both patients: lymphocyte alveolitis with granulomatous lesions on the transbronchial biopsy in patient one and positive leukocyte migration test in the presence of methotrexate in patient two. Early acute respiratory failure required high flow rate oxygen therapy with positive expiratory pressure ventilatory assistance. The course was rapidly favorable both for blood gases and radiographic presentation without corticosteroids. These two cases illustrate that pulmonary disease can be cured without corticosteroids despite severe respiratory failure at onset. This provides a further argument on reservations about using corticosteroids for suspected methotrexate-induced pneumonia.
1075. [Economic assessment of Caelyx versus topotecan in advanced ovarian cancer].
作者: Véronique Girre.;Eric Pujade-Lauraine.;Isabelle Durand-Zaleski.
来源: Bull Cancer. 2003年90卷11期983-8页
Ovarian cancer is the most frequent cause of death due to gynecologic malignancy in both the United States and in Europe. A phase III investigation compared second line treatment Caelyx with topotecan in patients with advanced epithelial ovarian carcinoma who failed a first-line platinum-containing regimen. A total of 474 patients were enrolled Although no significant advantage of Caelyx over topotecan with regards to overall survival and progression was found, there were fewer adverse events in the Caelyx arm and Caelyx had significantly better quality of life profile. We conducted a cost minimization analysis of both treatment arms. Costs were estimated from the viewpoint of the hospital, over the duration of the study period (12 weeks). The frequency of adverse events was derived from the trial's CRF, the treatment patterns of adverse events was estimated for each type of adverse event and each grade for a given type of adverse event. Costs included that of the drug and management of adverse events. Because of uncertainty on actual time spent in French hospitals, administration costs were not valued. Adverse events valued in the analysis were: stomatitis/ pharyngitis, PPE, nausea/vomiting diarrhea, anemia, thrombocytopenia, neutropenia, sepsis, fever. Drug costs and costs of blood products were valued using the purchase price by the hospital, costs of tests and hospital days were estimated from the hospital's accounting system. The drug cost per patient was 8,735 euros for Caelyx and 6,196 euros for topotecan, the cost of adverse events were 528 and 3,632 euros for Caelyx and topotecan respectively, due to the high rate of adverse events in patient treated with topotecan. The total costs were 9,279 and 9,938 for Caefyx and topotecan respectively.
1076. [Hsp90: how a chaperone becomes a pharmacological target].1080. [Tamoxifen, endometrial cancer and levonorgestrel intra-uterine device].
Although the adjuvant tamoxifen benefit/risk rate is unquestionable in breast cancer treatment, the increase of endometrial cancer in chemoprevention is about to be a real problem. In the studies currently published metrorragia in the main signal. Levonogestrel intra-uterine device has not proved its efficacy for the decrease of this risk.
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