Quimioterapia neoadjuvante em câncer localmente avançado do colo do útero Neoadjuvant chemotherapy in locally advanced cancer of the cervix

OBJETIVOS: avaliar a quimioterapia neoadjuvante no câncer localmente avançado do colo uterino, por meio da sua aceitabilidade, tolerabilidade, toxicidade, taxa de complicações cirúrgicas, taxa de resposta, taxa de operabilidade e sobrevida em 5 anos. MÉTODOS: foram incluídas 60 mulheres com câncer do colo uterino localmente avançado (IIB e IIIB), submetidas à quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina. Aquelas que se tornaram operáveis após a quimioterapia foram submetidas à cirurgia de Wertheim-Meigs, seguida de radioterapia pélvica complementar. Nas pacientes em que a cirurgia não foi possível após a quimioterapia, realizou-se radioterapia. RESULTADOS: o seguimento médio foi de 108 meses. A taxa de resposta global à quimioterapia foi de 80%, sendo 100% para o estádio IIB e 60% para o estádio IIIB. A porcentagem de pacientes operadas, após a quimioterapia foi de 65%. A sobrevida global em 5 anos para todo o grupo foi 62%. No grupo operado (n=34), a sobrevida global foi de 82,14%, independentemente do estádio inicial. No grupo não operado (n=18), a sobrevida em 5 anos foi 16,67%. CONCLUSÕES: A quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina no câncer do colo uterino localmente avançado é segura, com baixo índice de complicações e permitiu uma alta taxa de operabilidade.<br>PURPOSE: to evaluate neoadjuvant chemotherapy in locally advanced cervical cancer as to its acceptability, tolerability, toxicity, surgical complications, operability, response rate, and overall survival in 5 years. METHODS: sixty women with locally advanced cervical cancer (stages IIB and IIIB), who were submitted to neoadjuvant chemotherapy, were included. All patients were treated with doxorubicin-bleomycin-cisplatin. Those who had a good response, allowing a surgical approach, underwent the Wertheim-Meigs procedure. After surgery, they were submitted to pelvic radiotherapy. Those that could not be submitted to surgery after chemotherapy underwent total radiotherapy. RESULTS: the average follow-up was 108 months, and 80% of the patients had an overall response to neoadjuvant chemotherapy. In the IIB group, the response rate was 100%, and in the IIIB group it was 60%. The operability rate after neoadjuvant chemotherapy was 65%. The overall survival in 5 years was 62%. Comparing the operated group (n=34) with the nonoperated group (n=18), the overall survival in 5 years was 82.14 and 16.67%, respectively. CONCLUSIONS: neoadjuvant chemotherapy with doxorubicin-bleomycin-cisplatin for locally advanced cervical cancer is safe, with a low rate of side effects, and allowed a high operability rate

DNA histogram typing and DNA index measurements in 508 invasive breast carcinomas from fine-needle aspirates and imprint smears as opposed to formalin-fixed paraffin-embedded tissues

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Characterization of chemotherapy-induced morphonuclear modifications in the P388 leukaemia and the MXT mammary tumour models of the mouse.

Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cell cycle and by several modifications in the chromatin texture in accordance with the model or the drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nevertheless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Introduction of the cytological grading, the nuclear area, the DNA index and the DNA histogram type in the setting up of a score for ductal breast carcinoma

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prevention of ovarian damage induced by cyclophosphamide in adult female mice by hormonal manipulations.

Doses of 10 or 20 mg cyclophosphamide/kg body weight were administered daily to mice for up to 20 days. This caused significant reductions in the incidence of prenatal (developing) follicles and significant increases in atretic (degenerating) follicles within the ovaries. Attempts to prevent cyclophosphamide-induced damage by simultaneous treatment with oestrogen alone, oestrogen plus progesterone, or danazol (a synthetic androgen) demonstrated that danazol effectively prevented the ovarian damage. The efficacy of danazol was considered to be due to its ability to inhibit LH/FSH secretion and, indirectly, the development of new ovarian follicles.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Digital cell image analysis of feulgen-stained nuclei from human papillary, medullary, colloid, lobular and comedocarcinonlas of the breast

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

DNA histogram typing in retinoblastomas and neuroblastomas.

The nuclear DNA content characterization was carried out by means of both DNA index and DNA histogram type assessments in a series of 21 retinoblastomas, 11 neuroblastomas, 1 ganglioneuroblastoma, and 4 medulloblastomas. These measurements were performed by means of the cytophotometric digital cell image analyses of Feulgen-stained nuclei. The results indicate that as far as nuclear DNA content is concerned, retinoblastomas seem to be very different from neuroblastomas. In fact, in terms of DNA index, retinoblastomas are significantly more aneuploid than neuroblastomas. The DNA histogram type shows that the high level of aneuploidy found in retinoblastomas corresponds to genotypically polymorphic tumors, and this could reflect a serious degeneration of the genomic material in retinoblastomas. This type of degeneration seems to be much less frequent in neuroblastomas, which basically seem to be either diploid or hypertriploid.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Ploidy level determination and quantitative chromatin pattern description in pregnancy-associated breast cancers.

The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Galectin fingerprinting in tumor diagnosis. Differential expression of galectin-3 and galectin-3 binding sites, but not galectin-1, in benign vs malignant uterine smooth muscle tumors.

Cell-matrix interactions are governed by a distinct set of proteins, with 2 nonintegrin laminin-binding proteins, galectin-1 and galectin-3, providing 1 aspect. The expression patterns of laminin and the 2 galectins and galectin binding sites were quantitatively determined by means of computer-assisted microscopy with the aim of differentiating between 16 leiomyomas and 10 leiomyosarcomas of the uterus. Three quantitative variables were computed for each of the 5 histochemical markers: labeling index, which describes the percentage of tissue area specifically stained by a given marker; mean optical density which reflects the concentration of the marker; and concentrational heterogeneity, which characterizes the degree of heterogeneity of the marker distribution in the tumor tissue areas. The results reveal evident differences in the galectin-3-related parameters in the 2 tumors groups. Whereas the concentration of galectin-3 binding sites was significantly (P = .01) weaker in the leiomyosarcomas than in the leiomyomas, the percentages of tumor tissue expressing galectin-3 (P = .02) and its binding sites (P = .002) were significantly higher in the leiomyosarcomas than in the leiomyomas. Although significantly (P = .02) higher, the concentration of laminin was more heterogeneously distributed (P = .01) in the leiomyosarcomas than in the leiomyomas. In contrast, the levels of expression of galectin-1 and its accessible binding sites remained similar for both the leiomyomas and the leiomyosarcomas. Finally we document how the levels of expression of galectin-3 and its binding sites can be of assistance in reliably differentiating leiomyomas from leiomyosarcomas.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe