Expression of the classical and nonclassical HLA molecules in breast cancer

Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC) of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated) and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6%) out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9%) showed high expression of HLA-E. A large number (41, 78.8%) of the biopsies showed low expression of HLA-Ia, while 45 (86.5%) showed high expression of HLA-DQ and 36 (69.2%) underexpressed HLA-DR. Moreover, 24 (41.2%) of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2%) had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness.

Evaluation of clinical, ultrasonographic and hysteroscopic parameters in the differentiation of endometrial polyps and cancer of endometrium

Study Objective: To evaluate the diagnostic accuracy of transvaginal ultrasound and office hysteroscopy in the differentiation between endometrial polyps and endometrial adenocarcinoma. Design: This is a prospective 100 women longitudinal study, 24 to 80 years, submitted to hysteroscopic polypectomy (n = 80) or surgery due to endometrial adenocarcinoma (n = 20), from january 2010 to December 2011. Clinical, ultrasonographic and hysteroscopic parameters were analyzed and compared with histopathologic find. Statistical analysis were performed utilizing the Tukey, Kruskal-Wallis, Dunn and Mann-Whitney test, with a confidence interval of 95% and p\0, 05 statiscally significant. Setting: Botucatu Medical School. Intervention: Prospective analysis of clinical, ultrasonographic and hysteroscopic parameters in patients with diagnosis suspected of endometrial polyps and adenocarcinoma of endometrium were performed. According to the diagnosis, hysteroscopic polypectomy or pan hysterectomy with lymph node sampling was realized. After the surgery and histopathological study, statistical analysis of parameters was performed and the results were compared between groups. It was Research Ethics Committee approved. Measurements and Main Results: There were no differences between age, BMI, menopause, TH use and associated diseases among groups. The main symptom of endometrial cancer was the postmenopausal bleeding, affecting 84,2% of women against 34,8% of polypectomy group. The majority of women with endometrial polyps were asymptomatic. Transvaginal ultrasonography showed no ability to differentiate cases of endometrial cancer compared with the cases of endometrial polyps, considering the presence of endometrial thickness and blood flow on color Doppler. Office hysteroscopy showed significant changes in 75% of the adenocarcinoma cases, especially the presence of diffuse hypervascularity with atypical vessels. Conclusion: Still remains an inability to establish clinical parameters and reliable ultrasound imaging to differentiate endometrial polyps and cancer of endometrium. Attention should be given to hysteroscopic exams presenting diffuse endometrial hypervascularization with architectural distortion of the vessels. The recommendation of our service remains the systematic removal of all endometrial polyps.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antimicrobial, Cytotoxic and Antioxidant Activities and Determination of the Total Tannin Content of Bark Extracts Endopleura uchi

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of the genotoxic and antigenotoxic potential of Brassica oleracea L. var. acephala D.C. in different cells of mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Histological and immunohistochemical study of the expression of p53 and ki-67 proteins in the mucosa of the tongue, pharynx and larynx of rats exposed to cigarette smoke

Introduction: Head and neck cancers are linked to smoking. The most affected sites are the oral cavity, pharynx and larynx. Experimental studies show epithelial lesions caused by cigarette smoke. Objectives: To investigate in rats the effects of acute cigarette smoke exposure on the mucosa of the tongue, pharynx and larynx.Material and method: Wistar rats were allocated into two groups of 20 animals: CG (control) receiving food and water ad libitum and TG (Tobacco) exposed to the smoke of 40 cigarettes/day for 60 days. Biopsy of their tongues, pharynxes and larynxes were subjected to histopathological, histomorphometric and immunohistochemical studies of protein p53 and ki-67.Result: The histological analysis of tongue from the Tobacco group revealed epithelial hyperplasia (90%), basal cell hyperplasia (95%) and mild to moderate dysplasia (85%). In pharynx showed basal cell hyperplasia (85%), dysplasia (25%) and vascular congestion (95%). In larynx showed basal cell hyperplasia (70%), epithelial hyperplasia (55%), congestion (100%) and inflammatory infiltrate (25%). Morphometric analysis revealed that keratin layer thickness was greater in the tobacco group. P53 immunoexpression was negative in both groups. Ki-67 immunoexpression was positive in basal cell nuclei but in parabasal cell nuclei it was positive only in the Tobacco group.Conclusions: The exposure of animals to cigarette smoke for 60 days resulted in benign lesions. The duration of exposure was not enough to cause the development cancer, as confirmed by the negative expression of p53 protein in all slides examined. Analysis of ki-67 expression showed intense epithelial proliferation in response to damage.

Genotyping of AR and PSA polymorphisms in a patient with Klinefelter syndrome, non-Hodgkin lymphoma, and adenocarcinoma of the prostate

It has been hypothesized that the AR (androgen receptor) gene binds the two PSA (prostate-specific antigen) alleles with differing affinities and may differentially influence prostate cancer risk. In this article, we report a case of adenocarcinoma of the prostate in a 56-year-old man with Klinefelter syndrome (47,XXY) and non-Hodgkin lymphoma, as well as the AR and PSA genotype. AR and PSA gene polymorphisms were analyzed by polymerase chain reaction-based methods using DNA from peripheral white blood cells and the prostate cancer. We determined the methylation status of the AR gene on the X chromosome. The patient presents with the AG genotype for the ARE-I (androgen response element) region of the PSA gene. We detect the presence of two short AR alleles with 19 and 11CAG repeats each. Unmethylated alleles were demonstrated for both. The shorter allele was inactive in more than 60% of total DNA in both control blood and prostate cancer cells. The presence of short AR alleles and the G allele of the PSA gene may contribute to the development of prostate cancer in a 47,XXY patient. (C) 2004 Elsevier B.V. All rights reserved.

Perineural Invasion in Aggressive Skin Carcinomas of the Head and Neck

Introduction: Perineural invasion is a well-recognized form of cancer dissemination. However, it has been reported only in few papers concerning cutaneous carcinomas ( basal cell, BCC, and squamous cell, SCC). Moreover, the incidence is considered to be very low. Niazi and Lambert [Br J Plast Surg 1993; 46: 156-157] reported only 0.18% of perineural invasion among 3,355 BCCs. It is associated with high-risk subtypes, as morphea-like, as well as with an increased risk of local recurrence. No paper was found in the literature looking for perineural invasion in very aggressive skin cancers with skull base extension, with immunohistochemical analysis. Methods: This is a retrospective review, including 35 very advanced skin carcinomas with skull base invasion (24 BCCs and 11 SCCs, operated on at a single institution from 1982 to 2000). Representative slides were immunohistochemically evaluated with antiprotein S-100, in order to enhance nerve fibers and to detect perineural invasion. The results were compared to 34 controls with tumors with a good outcome, treated in the same time frame at the same Institution. Results: Twelve (50.0%) of the BCCs with skull base invasion had proven perineural invasion, as opposed to only 1 (4.6%) of the controls, and this difference was statistically significant (p < 0.001). Regarding SCCs, 7 aggressive tumors (63.6%) showed perineural invasion compared to only 1 (10.0%) of the controls, but this difference did not reach significance (p=0.08), due to the small number of cases. Conclusions: In this series, it was demonstrated that immunohistochemically detected perineural invasion was very prevalent in advanced skin carcinomas. In addition, it was statistically associated with extremely aggressive BCCs with skull base invasion. Copyright (c) 2008 S. Karger AG, Basel

Screening for In Vitro and In Vivo Antitumor Activities of the Mushroom Agaricus Blazei

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of uterine cervix constriction on Wistar rats

Purpose: To verify if uterine cerclage can induce craniosynostosis or any cranial deformity in new born Wistar rats. Methods: One pregnant female Wistar rat underwent laparotomy on day 18 of gestation and the uterus cervix was closed with a 3-0 nylon suture to avoid delivery, that occurs normally on the 21 day. The suture was released after 48 hours beyond the normal gestation period. The female rat delivered 11 pups. Six surviving rats from the delivery (group A - constrained group). Two rats were born from another mother and in the same age were used as control group (group B - 2 nonconstrained controls) were allowed to grow. They were sacrificed 1.2 years after their birth all the eight animals. Linear measurement, routine histology and computed tomography of the skull were performed at the time of their death to evaluate the cranial asymmetries by mesurements of the anatomical landmarks of the craniofacial skeleton of the rats on the two groups and compared then. Results: We did not observe statistically significant differences in any of the compared measurements (p>0.05) obtained through the morphologic and radiologic methods. Histologic examinations did not reveal any sign of premature fusion or suture imbrications. Critical decrease in longitudinal body size was noticed as the limbs too in all the animals of group A. Conclusion: Constriction of uterine cervix leads to fetus suffering, even death for a few animals, associated to small body size, but not to craniosynostosis.

Abnormal cell-cycle expression of the proteins p27, mdm2 and cathepsin B in oral squamous-cell carcinoma infected with human papillomavirus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Late morfofunctional alterations of the Sertoli cell caused by doxorubicin administered to prepubertal rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Repercussions of castration and vasectomy on the ductal system of the rat ventral prostate

Diseases. such as cancer and benign prostatic hyperplasia, are related to disruption of the mechanism regulating the balance between cell proliferation and apoptosis in prostatic cells. Since castration and vasectomy might alter that balance, this study evaluates the cell proliferation, apoptosis and height of the secretory epithelium of the ventral-prostate ductal system post-castration and vasectomy. Immunohistochemical (PCNA and Ki67), cytochemical (Fuelgen reaction) and morphometric investigation have been carried out. Cell proliferation indices decreased significantly in both regions of the ventral-prostate ductal system after castration compared to the sham-operated group. The apoptotic index increased significantly after 48 h, declining 7 days post-castration. The cell proliferation indices did not differ after 48 h significantly; however, they increased 7 days post-vasectomy in both regions. The apoptotic index did not differ significantly in either time post-vasectomy. Castration caused an imbalance in favor of apoptosis, whereas vasectomy caused an imbalance in favor of cell proliferation. (c) 2005 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae)

Ethnopharmacological relevance: Virola surinamensis (Myristicaceae), popularly known as mucuiba, ucuuba or ucuuba do igapo is a large tree that grows abundantly in Varzea forest and on river banks in the Brazilian states of Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed folk remedy in its natural form for the treatment of ulcer, gastritis inflammation and cancer.Aim of the study: The present work evaluated the pharmacological activity of the resin obtained from bark of V surinamensis as antiulcerogenic in experimental in vivo model in order to observe whether its traditional use is justified.Materials and methods: The preventive action of ethanolic extract of V surinamensis was evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa.Results: Oral administration of acidified ethanol solution produced severe hemorrhagic lesions in glandular mucosa with ulcerative lesion of 50 +/- 11.5 mm. In animals pretreated with V surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury of 2.40 +/- 0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same dose, also reduced significantly (p < 0.05) the formation of gastric lesions induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%) when compared to animals treated with vehicle. The extract from V surinamensis exerts gastroprotective action only when this extract contacts gastric mucosa (oral route) with. increased pH values and reduced H(+) concentration of gastric contents. The ethanolic extract of V surinamensis resin was analyzed by TLC and spectrometric methods (NMR and ES-MS) and the main constituent of this extract was epicatechin.Conclusions: We suggest that the epicatechin present in V surinamensis resin may be among active principles responsible for the antiulcer activity shown by the tested resin but their used suggest carefulness because toxicological symptoms mentioned by population. (C) Published by Elsevier B.V.

Cyclin D1 gene polymorphism as a risk factor for squamous cell carcinoma of the upper aerodigestive system in non-alcoholics

Squamous cell carcinoma of the upper aerodigestive tract (UADT) is associated with environmental factors, especially tobacco and alcohol consumption. Genetic factors, including cyclin D1 (CCND1) polymorphism have been suggested to play an important rote in tumorigenesis and progression of UADT cancer. To investigate the relationship between CCND1 polymorphism on susceptibility for UADT cancers, 147 cancer and 135 non-cancer subjects were included in this study. CCND1 genotype at codon 242(G870A) in exon 4 was undertaken using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Significant odds ratio (OR) of the AA + GA genotypes [OR = 7.5 (95% Cl: 1.4-39.7)] was observed in non-drinkers but for non-smokers a non-significant [OR = 5.4 (95% Cl: 0.9-31.4)] was found in the adjusted model. These results suggest that allele A may be a risk factor for UADT cancer, especially in non-alcoholics. However, further epidemiological studies are needed to establish the exact role of CCND1 polymorphism and the development of UADT cancers. (C) 2004 Elsevier Ltd. All rights reserved.