Penectomia em equino com carcinoma de células escamosas

The presence of increased volume in penis and prepuce of horses can be of neoplastic or non-neoplastic origin. Squamous cell carcinoma (SCC), papilloma, fibropapiloma, melanoma and sarcoidorigin. Squamous cell carcinoma (SCC), papilloma, fibropapilloma, melanoma and sarcoid are detached as neoplastic causes. The non-neoplastic causes can be parasitic as habronemiasis and pythiosis, or inflammation, resulting in the formation of exuberant granulation tissue. The penile disorders can be easily confused with each other because they have similar clinical signs. Among epithelial neoplasms affecting penis and prepuce, squamous cell carcinoma is the most common in horses. Thus, it was aimed to report a case of squamous cell carcinoma in a horse and describe the main differential diagnosis for this disease. The additional tests to obtain an accurate diagnosis and the institution of appropriate treatment are essential for the satisfactory repair of penile neoplasms in this species.

Modulação da imunidade adaptativa por produtos solúveis de células de carcinoma espinoceular de cabeça e pescoço (HNSCC): um papel da galanina derivada do tumor?

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

Estudo comparativo da expressão da survivina na citologia esfoliativa da mucosa bucal de pacientes com carcinoma de células escamosas intra-bucal e fumantes crônicos

Survivin protein is an inhibitor of apoptosis that plays a role in cell cycle control and the mechanism of carcinogenesis. The aim of this study was to verify the clinic pathological correlation of survivin expression in exfoliative cytology of chronic smokers, mucosa of patients with intra-oral squamous cell carcinoma (OSCC) and also from mucosa after surgical removal of OSCC. Patients were divided in 03 groups: Group 1: 26 patients who smoked more than 20 cigarettes/day/10years with no history of oral malignant neoplasm, or any clinical sign visible at examination. Group 2: 26 patients who had OSCC and Group 3: 22 patients surgically treated of OSCC for at least 01 month. Immunohistochemistry of the smears from each group was analyzed by light microscopy to extent and intensity of survivin positive cells. Survivin expression was observed in 100% of cases in group 1, 88.5% in group 2 and 100% in group 3. Groups 1 and 3 showed cytoplasmic expression in 100% of the cases, while group 2 showed it in 87.5%. Cytoplasmic and nuclear expression was 7.69% observed only in group 2. The results were association with clinicopathological data by Fisher's exact test and it was significant to smoke cessation in group 2 on intensity (p=0.015) of survivin expression. The intensity of survivin expression was related to smoking cessation in group 2. Smoking history (pack/years) showed no influence survivin expression

Modulação da imunidade adaptativa por produtos solúveis de células de carcinoma espinoceular de cabeça e pescoço (HNSCC): um papel da galanina derivada do tumor?

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

Estudo comparativo da expressão da survivina na citologia esfoliativa da mucosa bucal de pacientes com carcinoma de células escamosas intra-bucal e fumantes crônicos

Survivin protein is an inhibitor of apoptosis that plays a role in cell cycle control and the mechanism of carcinogenesis. The aim of this study was to verify the clinic pathological correlation of survivin expression in exfoliative cytology of chronic smokers, mucosa of patients with intra-oral squamous cell carcinoma (OSCC) and also from mucosa after surgical removal of OSCC. Patients were divided in 03 groups: Group 1: 26 patients who smoked more than 20 cigarettes/day/10years with no history of oral malignant neoplasm, or any clinical sign visible at examination. Group 2: 26 patients who had OSCC and Group 3: 22 patients surgically treated of OSCC for at least 01 month. Immunohistochemistry of the smears from each group was analyzed by light microscopy to extent and intensity of survivin positive cells. Survivin expression was observed in 100% of cases in group 1, 88.5% in group 2 and 100% in group 3. Groups 1 and 3 showed cytoplasmic expression in 100% of the cases, while group 2 showed it in 87.5%. Cytoplasmic and nuclear expression was 7.69% observed only in group 2. The results were association with clinicopathological data by Fisher's exact test and it was significant to smoke cessation in group 2 on intensity (p=0.015) of survivin expression. The intensity of survivin expression was related to smoking cessation in group 2. Smoking history (pack/years) showed no influence survivin expression

In Silico Analysis and Immunohistochemical Characterization of NaPi2b Protein Expression in Ovarian Carcinoma With Monoclonal Antibody Mx35

Introduction: Ovarian adenocarcinoma is frequently detected at the late stage, when therapy efficacy is limited and death occurs in up to 50% of the cases. A potential novel treatment for this disease is a monoclonal antibody that recognizes phosphate transporter sodium-dependent phosphate transporter protein 2b (NaPi2b). Materials and Methods: To better understand the expression of this protein in different histologic types of ovarian carcinomas, we immunostained 50 tumor samples with anti-NaPi2b monoclonal antibody MX35 and, in parallel, we assessed the expression of the gene encoding NaPi2b (SCL34A2) by in silico analysis of microarray data. Results: Both approaches detected higher expression of NaPi2b (SCL34A2) in ovarian carcinoma than in normal tissue. Moreover, a comprehensive analysis indicates that SCL34A2 is the only gene of the several phosphate transporters genes whose expression differentiates normal from carcinoma samples, suggesting it might exert a major role in ovarian carcinomas. Immunohistochemical and mRNA expression data have also shown that 2 histologic subtypes of ovarian carcinoma express particularly high levels of NaPi2b: serous and clear cell adenocarcinomas. Serous adenocarcinomas are the most frequent, contrasting with clear cell carcinomas, rare, and with worse prognosis. Conclusion: This identification of subgroups of patients expressing NaPi2b may be important in selecting cohorts who most likely should be included in future clinical trials, as a recently generated humanized version of MX35 has been developed.

Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid Subgroup Analysis from a Randomized Phase 3 Study

Introduction: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma. Methods: Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC. Results: Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA. Conclusion: In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.

Immunohistochemistry Analysis of Proteins Related with Apoptosis as Prognostic Factor in Epidermoid Carcinoma of Penis

The aim was to analyze the protein expression of apoptotic genes caspase-3, caspase-8 and bcl-2 with the immunohistochemistry technique, correlating with tumor grade (I, II and III) and with the patient survival in order to understand the basic mechanism of tumoral transformation. The immunohistochemistry reactions on 50 samples of squamous cell carcinoma were carried out with the avidin-biotin immunoperoxidase method and antigen recovery. The analyses were made using the graduation method "in crosses" (0 to 4 crosses - no stain to more than 75% of positives cells) and in categories (low, intermediate, high) of the cytoplasm immunoreactivity of the epidermoid penile carcinoma cells. It was observed a statistically significant difference when the expression of caspase-3 were compared with the grades land II of the tumor (p=0.0010) and when comparing the patient survival with the grades I and II of the tumor (p=0.0212). The protein bcl-2 was more expressed than caspase-3 and caspase-8 proteins, suggesting that the apoptotic rate in this carcinoma is low. The higher expression of the anti-apoptotic protein bcl-2 suggests a higher preservation of the tumoral cells.

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. Objective: This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Material and Methods: Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. Results: The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). Conclusions: S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

The goals of this study are to evaluate in vitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, gamma-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 mu g/mL Selol plus 5 x 10(12) particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 mu g/mL Selol and 5 x 10(12) -2.5 x 10(13) particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (+/- 3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (+/- 0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach. (C) 2012 American Institute of Physics. [doi: 10.1063/1.3680541]

Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma

Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for beta-globin (internal control), and 10 (15.9%) were beta-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas.

SET protein accumulates in HNSCC and contributes to cell survival: Antioxidant defense, Akt phosphorylation and AVOs acidification

Objectives: Determination of the SET protein levels in head and neck squamous cell carcinoma (HNSCC) tissue samples and the SET role in cell survival and response to oxidative stress in HNSCC cell lineages. Materials and Methods: SET protein was analyzed in 372 HNSCC tissue samples by immunohistochemistry using tissue microarray and HNSCC cell lineages. Oxidative stress was induced with the pro-oxidant tert-butylhydroperoxide (50 and 250 mu M) in the HNSCC HN13 cell lineage either with (siSET) or without (siNC) SET knockdown. Cell viability was evaluated by trypan blue exclusion and annexin V/propidium iodide assays. It was assessed caspase-3 and -9, PARP-1, DNA fragmentation, NM23-H1, SET, Akt and phosphorylated Akt (p-Akt) status. Acidic vesicular organelles (AVOs) were assessed by the acridine orange assay. Glutathione levels and transcripts of antioxidant genes were assayed by fluorometry and real time PCR, respectively. Results: SET levels were up-regulated in 97% tumor tissue samples and in HNSCC cell lineages. SiSET in HN13 cells (i) promoted cell death but did not induced caspases, PARP-1 cleavage or DNA fragmentation, and (ii) decreased resistance to death induced by oxidative stress, indicating SET involvement through caspase-independent mechanism. The red fluorescence induced by siSET in HN13 cells in the acridine orange assay suggests SET-dependent prevention of AVOs acidification. NM23-H1 protein was restricted to the cytoplasm of siSET/siNC HN13 cells under oxidative stress, in association with decrease of cleaved SET levels. In the presence of oxidative stress, siNC HN13 cells showed lower GSH antioxidant defense (GSH/GSSG ratio) but higher expression of the antioxidant genes PRDX6, SOD2 and TXN compared to siSET HN13 cells. Still under oxidative stress, p-Akt levels were increased in siNC HN13 cells but not in siSET HN13, indicating its involvement in HN13 cell survival. Similar results for the main SET effects were observed in HN12 and CAL 27 cell lineages, except that HN13 cells were more resistant to death. Conclusion: SET is potential (i) marker for HNSCC associated with cancer cell resistance and (ii) new target in cancer therapy. (C) 2012 Elsevier Ltd. All rights reserved.

Intratumoral Lymphatic Vessel Density in Vulvar Squamous Cell Carcinomas: A Possible Association With Favorable Prognosis

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one-and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive'' group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive'' group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.

Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip

The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5 gamma 2 chain as well as alpha 3, beta 1 subunits of alpha 3 beta 1 heterodimer and beta 4 subunit of integrin alpha 6 beta 4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of beta 1, beta 4 and alpha 3 integrins, and SISCCs lacked beta 1, beta 4 and alpha 3 integrins in the invasive front. AC cases were negative for the Ln-5 gamma 2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5 gamma 2 chain expression in the invasive front of the tumor. Integrin beta 1, beta 4 and alpha 3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5 gamma 2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype. (C) 2012 Elsevier GmbH. All rights reserved.