Espectroscopia FT-Raman no diagnóstico do carcinoma espinocelular de mucosa bucal: estudo ex vivo em humanos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fatores prognósticos do carcinoma espinocelular de gengiva inferior: análise retrospectiva de 264 casos

Pós-graduação em Odontologia - FOA

Fatores prognósticos e análise de sobrevida de pacientes diagnosticados com carcinoma espinocelular nos 10 primeiros anos do Centro de Oncologia Bucal da Unesp, Campus de Araçatuba

Objetivo: Estimar as probabilidades acumuladas de sobrevida dos pacientes diagnosticados com carcinoma espinocelular nos 10 primeiros anos do Centro de Oncologia Bucal da UNESP, Campus de Araçatuba, de 1991 a 2000, observadas até 2005, estabelecendo os possíveis fatores prognósticos significativos para o óbito. Méttodo: A análise de sobrevida foi realizada em uma coorte de 280 pacientes com carcinoma espinocelular, no Centro de Oncologia Bucal da Faculdade de Odontologia de Araçatuba, UNESP, entre 1991 e 2000. Para avaliar a associação entre as variáveis independentes e o óbito, realizou-se o teste Log Rank. A probabilidade do teste com p-valor menor que 0,25 ficou estabelecida para a inclusão das covariáveis no processo de ajustamento do modelo. A sobrevida foi estimada pelo método de produto limite de Kaplan-Meier. Os fatores prognósticos foram estimados pelo modelo de riscos proporcionais de Cox, calculando-se razão da função de risco (HR). A análise de resíduo foi realizada para verificar o ajuste do modelo. Resultados: As taxas de probabilidades acumuladas de sobrevida de 280 pacientes, para os casos em estádio IV, foram, 56,74%, 32,13%, 23,71% e 20,57%, respectivamente, até 1, 2, 3 e 5 anos após o diagnóstico. Pacientes no estádio I apresentaram sobrevida em 5 anos de 81,73%. O estadiamento clínico da doença no diagnóstico foi o único fator prognóstico definido no processo de ajuste de modelo. A estimativa da razão da função de riscos de morrer em pacientes diagnosticados no estádio III (HR=3,3), é praticamente três vezes o risco daqueles em estádio I; da mesma forma, o risco de morrer dos diagnosticados em estádio IV (HR=6,17) é cerca de seis vezes ao daqueles em estádio I. Conclusões: A covariável que permaneceu no modelo final foi estadiamento clínico no momento do diagnóstico, sendo, pois, o único fator prognóstico.

Efeito das oncoproteínas virais E6 e E7 do HPV-16 na resposta de células T de pacientes com carcinoma espinocelular de cabeça e pescoço

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

Expressão proteica das enzimas metabolizadoras de drogas no carcinoma de células escamosas de boca em pacientes jovens

Pós-graduação em Biopatologia Bucal - ICT

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis

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

Análise da proteína EGFR em carcinoma espinocelular de lábio

Pós-graduação em Biopatologia Bucal - ICT

Carcinoma escamoso oral: análise retrospectiva de 185 casos

The squamous cell carcinoma is the most common malignancy in the oral cavity, representing over 90% of cancers in this region. This study aimed to conduct an epidemiological study of oral squamous carcinoma cases diagnosed by the Department of Pathology, Department of Pathology and Clinical Propaedeutics in the Dentistry Faculty of Araçatuba - UNESP, in the period between 1995 and 2005. 185 cases were studied, it was observed that the oral floor and tongue were the sites most affected, with predominance in males, white race and aged between 41 and 60 years, noting that the majority of patients were smokers. Knowledge of these data is important for the dental surgeon to act preventively, contributing to early diagnosis of cancer.

Amino acids in squamous cell carcinomas and adjacent normal tissues from patients with larynx and oral cavity lesions

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Carcinoma de células escamosas em glândula mamária de gata doméstica

Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years before, but with previous administration of contraceptives. At the physical examination, it was observed ulcer between the caudal abdominal mammary glands. The occurrence of skin or mammary neoplasia was conceived. The following complementary tests were requested: complete blood count, serum biochemical profi le (renal and hepatic), chest radiographs, abdominal ultrasound, and incisional biopsy of the ulcerated region periphery, followed by classic histopathology. The lesion histopathology was compatible with squamous cell carcinoma of the mammary gland. Due to such a diagnosis, bilateral mastectomy was recommended. The material obtained during the surgical procedure was sent for anatomopathological analysis. Microscopically, surgical margins infi ltration and a regional lymph node were verifi ed. The owner was advised of the need for complementary therapies and medical monitoring of the cat. However, there was no return. It is noteworthy that the animal’s physical and laboratory examinations showed no neoplasia in other regions, being the squamous cell carcinoma of the mammary gland considered primary. Discussion: The malignant mammary neoplasia genesis in feline species, in general, seems to be related to steroid hormones. The ovariectomized females are less likely to develop the disease when compared to intact cats, but there is no protective effect of surgery on those spayed after two years of age regarding the appearance of the neoplasia. Thus, at the time the reported patient was ovariectomized, this effect no longer occurred. The synthetic progestins regularly used to prevent estrus increase by three times the risk of breast carcinomas onset. In humans, there is no clear defi nition of the etiology and pathogenesis of mammary squamous cell carcinoma. However, it has been suggested its association with extreme forms of squamous metaplasia present in pre-existing mammary adenocarcinoma, besides cysts, chronic infl ammations, abscesses and mammary gland adenofi bromas. In a hypothetical way, this etiology could also be related to the feline mammary carcinoma, although, for the case at issue, the exogenous and endogenous hormonal infl uence should not be excluded. It has been reported that mammary squamous cell carcinomas in cats are classifi ed in grades II and III (ie, moderately and poorly differentiated, respectively). Thus, they are considered tumors with more unfavorable prognosis. However, the monitoring of the clinical course, in order to evaluate possible recurrence of the neoplasia and metastases to distant sites, was not possible as the animal under discussion did not return. The squamous cell carcinoma is the most common skin tumor in feline species, despite the primary location in the mammary gland. It is, therefore, important to differentiate squamous cell carcinoma originated in the breast from histological types derived from skin. The description of this special and rare feline mammary carcinoma is important due to its particular characteristics and potential for malignancy.

The clinical impact of p16 status in fine-needle aspirates of cervical lymph node metastasis of head and neck squamous cell carcinomas

Lymph node involvement is prognostically the most determinant clinical factor for patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic procedures and the most accurate diagnostic staging tool for the neck. Patients with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are localized either in the palatal tonsils or the base of tongue and frequently present with lymph node metastases. We analyzed the correlation and reliability of p16 expression of the FNA of the lymph node metastasis with the immunohistochemical expression of p16 of the same lymph node metastasis and its corresponding primary tumor, as it could be of importance for determining the localization and different prognosis of the primary tumor. 54 HNSCC patients were evaluated, p16 expression of the primary tumors and their lymph node metastases correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node metastases was taken before the treatment. The positive cytological and immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16-negative lymph node metastases 15 FNA were p16-negative, whereas two samples were p16-positive. In our view, a cytological p16 analysis of cervical lymph node metastasis can facilitate the correct localization of the primary tumor and discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their significantly diverse prognosis.

Retinoid -induced regression of human head and neck squamous cell carcinomas is associated with the induction of a pro -inflammatory response

Retinoids are Vitamin A derivatives that are effective chemopreventative and chemotherapeutic agents for head and neck squamous cell carcinomas (HNSCC). Despite the wide application of retinoids in cancer treatment, the mechanism by which retinoids inhibit head and neck squamous cell carcinomas is not completely understood. While in vitro models show that drugs affect cell proliferation and differentiation, in vivo models, such as tumor xenografts in nude mice drugs affect more complex parameters such as extracellular matrix formation, angiogenesis and inflammation. Therefore, we studied the effects of retinoids on the growth of the 22B HNSCC tumors using a xenograft model. In this system, retinoids had no effect on tumor cell differentiation but caused invasion of the tumor by inflammatory cells. Retinoid induced inflammation lead to tumor cell death and tumor regression. Therefore, we hypothesized that retinoids stimulated the 22B HNSCC xenografts to produce a pro-inflammatory signal such as chemokines that in turn activated host inflammatory responses. ^ We used real time quantitative RT-PCR to measure cytokine and chemokine expression in retinoid treated tumors. Treatment of tumors with an RAR-specific retinoid, LGD1550, had no effect on the expression of TNFα, IL-1α, GROα, IP-10, Rantes, MCP-1 and MIP-1α but induced IL-8 mRNA 5-fold. We further characterized the retinoid effect on IL-8 expression on the 22B HNSCC and 1483 HNSCC cells in vitro. Retinoids increased IL-8 expression and enhanced TNFα-dependent IL-8 induction. In addition, retinoids increased the basal and TNFα-dependent expression of MCP-1 but decreased the basal and TNFα dependent expression of IP-10. The effect of retinoids on IL-8 and MCP-1 expression was very rapid with increased levels of mRNA detected within 1–2 hours. This effect did not require new protein synthesis and did not result from mRNA stabilization. Both RAR and RXR ligands increased IL-8 expression whereas only RAR ligands activated MCP-1 expression. ^ We identified a functional retinoid response element in the IL-8 promoter that was located adjacent to the C/EBP-NFkB response element. TNFα treatment of the 22B cells caused rapid, transient and selective acetylation of regions of the IL-8 promoter associated with the NFkB response element. Co-treatment of the cells with retinoids plus TNF increased the acetylation of chromatin in this region without altering the kinetics of acetylation. These results demonstrate that ligand activated retinoid receptors can cooperate with NFkB in histone acetylation and chromatin remodeling. We believe that in certain HNSCC tumors this cooperation and the resulting enhancement of IL-8 expression can induce an inflammatory response that leads to tumor regression. We believe that the induction of inflammation in susceptible tumors, possibly coupled with cytotoxic interventions may be an important component in the use of retinoids to treat human squamous cancers. ^

FHIT gene alterations in head and neck squamous cell carcinomas.

To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC cell lines for deletions within the FHIT locus by Southern analysis, for allelic losses of specific exons FHIT by fluorescence in situ hybridization (FISH) and for integrity of FHIT transcripts. Three cell lines exhibited homozygous deletions within the FHIT gene, 55% (15/25) showed the presence of aberrant transcripts, and 65% (13/20) showed the presence of multiple cell populations with losses of different portions of FHIT alleles by FISH of FHIT genomic clones to interphase nuclei. When the data obtained by FISH and by reverse transcriptase-PCR analyses are combined, 22 of 26 cell lines showed alterations of at least one allele of the FHIT gene. Our data indicate that the FHIT gene is disrupted in HNSCCs and hence, loss of FHIT function may be important in the development and/or progression of head and neck cancers.

Merkel cell polyomavirus-specific CD8 T cells in Merkel cell carcinoma: T cell receptor diversity & novel immune therapies

Thesis (Ph.D.)--University of Washington, 2016-06