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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Sleep Loss and its Health Impact Among Family Caregivers of Persons with a Primary Malignant Brain Tumor

Pawl, Jean 14 December 2011 (has links)
Sleep impairments for caregivers are multifactorial. Assumptions are that caregivers of those with primary malignant brain tumors (PMBT) are similar to caregivers of persons with dementia as cognitive impairments are present at diagnosis. The shorter trajectory of PMBTs and rapid deterioration of recipients’ health may influence sleep in caregivers of persons with a PMBT. The purposes of this study were to use a sleep impairment model to characterize caregiver sleep using objective and subjective measures, and to examine sleep loss effects on psychosocial and physiologic health outcomes. A secondary data analysis using baseline data from a larger study of mind-body interactions in caregivers of family members with PMBTs was used. Caregiver data included standardized questionnaires, serum blood draw, and three-day sleep-wake activity data from an accelerometer. Analyses included descriptive statistics, correlations, t-tests, and hierarchical regression models. Caregivers (N = 133) were White (94%), female (69.2%) spouses (75.2) and on average 52 years old (SD = 11.8). Care recipients were mainly White males of similar age with a highly malignant glioma (57.4%). Sleep latency was longer (35 min, SD = 34.5), with shorter total sleep time (TST) (357 min, SD = 84.6) and more frequent wake after sleep onset (WASO; 15.1%, SD = 9.2) than in the general population. Caregivers reported high anxiety (59.4%). Caregiver comorbidities and care recipient functioning explained higher perceptions of health (R2 = 26, F(2, 84) = 14.94, p < .001). Whereas, longer TST, more WASO and poorer sleep quality explained poorer quality of life (R2 = .27, F(4, 66) = 6.19, p < .001). Sleep loss variables explained little variance in physical health status, interleukin-1ra and interleukin-6 levels, fatigue, depressive symptoms, spiritual health, social support, and work limitations. Nurses need to assist caregivers with anxiety management and ways to improve sleep at time of PMBT diagnosis. Sleep impairments place these caregivers at risk for physical and mental health problems, and compromise their ability to continue in the role.
52

Ovarian tumor risk factors study in a south medical center in Taiwan

Wu, Wei-Wen 05 July 2012 (has links)
This study discusses main risk factors of ovarian tumor to determine a tumor type. Since symptoms of ovarian tumor are not obvious as the tumors are located in pelvic, the ovarian tumor is difficult to detect. The symptoms are mostly stomach or lower abdomen swellings, which are often ignored. The probability of ovarian cancer is lower than cervical cancer, but the mortality rate is the highest of all gynecologic diseases. The study uses statistical methods to analyze risk factors of patients to determine the tumor type and an early treatment in order to reduce the death rate. The sources of the studies are from Kaohsiung Veterans General Hospital and are classified according to different cases of tumors based on ultrasound checks and other relevant risk factors, such as ages and tumor marks so as to provide a determined method to distinguish among benign, borderline and malignant ovarian tumors in order to create appropriate classification criteria for followups, surgeries, and references for tracking. To differentiate between malignant and nonmalignant (benign and borderline) cases, we use risk factors to construct classification and regression trees so as to help physicians to determine the tumor type. In the situation in which the non-malignant tumor may be determined, we use logistic regression model according to the degree of influence of risk factors to further classify between benign and borderline tumors. The aforementioned process can determine tumor types precisely and can also determine surgery types so as to help determining whether patients would need a follow-up.
53

脳腫瘍の遺伝子治療

水野, 正明, 吉田, 純, Mizuno, Masaaki, Yoshida, Jun 05 1900 (has links)
No description available.
54

Enhancing Dendritic Cell Migration to Drive Antitumor Responses

Batich, Kristen Anne January 2017 (has links)
<p>The histologic subtypes of malignant glial neoplasms range from anaplastic astrocytoma to the most deadly World Health Organization (WHO) Grade IV glioblastoma (GBM), the most common primary brain tumor in adults. Over the past 40 years, only modest advancements in the treatment of GBM tumors have been reached. Current therapies are predominantly for palliative endpoints rather than curative, although some treatment modalities have been shown to extend survival in particular cases. Patients undergoing current standard of care therapy, including surgical resection, radiation therapy, and chemotherapy, have a median survival of 12-15 months, with less than 25% of patients surviving up to two years and fewer than 10% surviving up to five years. A variety of factors contribute to standard treatment failure, including highly invasive tumor grade at the time of diagnosis, the intrinsic resistance of glioma cells to radiation therapy, the frequent impracticality of maximal tumor resection of eloquent cortical structures, and the fragile intolerance of healthy brain for cytotoxic therapies. Treatment with immunotherapy is a potential answer to the aforementioned problems, as the immune system can be harnessed and educated to license rather potent antitumor responses in a highly specific and safe fashion. One of the most promising vehicles for immunotherapy is the use of dendritic cells, which are professional antigen-presenting cells that are highly effective in the processing of foreign antigens and the education of soon-to-be activated T cells against established tumors. The work outlined in this dissertation encompasses the potential of dendritic cell therapy, the current limitations of reaching full efficacy with this platform, and the recent efforts employed to overcome such barriers. This work spans the characterization and preclinical testing of utilizing protein antigens such as tetanus-diphtheria toxoid to pre-condition the injection site prior to dendritic cell vaccination against established tumors expressing tumor-specific antigens. </p><p>Chapter 1 comprises an overview of the current standard therapies for malignant brain tumors. Chapters 2 and 3 provide a review of immunotherapy for malignant gliomas in the setting of preclinical animal models and discuss issues relevant to the efficacy of dendritic cell vaccines for targeting of GBM. Chapters 4 provides the rationale, methodology, and results of research to improve the lymph node homing and immunogenicity of tumor antigen-specific dendritic cell vaccines in mouse models and in patients with newly diagnosed GBM. Chapter 5 delineates the interactions discovered through efforts in Chapter 4 that comprise protein antigen-specific CD4+ T cell responses to induced chemokines and how these interactions result in increased dendritic cell migration and antitumor responses. Lastly, Chapter 6 discusses the future utility of migration of DC vaccines as a surrogate for antitumor responses and clinical outcomes. </p><p>This dissertation comprises original research as well as figures and illustrations from previously published material used to exemplify distinct concepts in immunotherapy for cancer. These published examples were reproduced with permission in accordance with journal and publisher policies described in the Appendix. </p><p>In summary, this work 1) identifies inefficient lymph node homing of peripherally administered dendritic cells as one of the glaring barriers to effective dendritic cell immunotherapy, 2) provides answers to overcome this limitation with the use of readily available pre-conditioning recall antigens, 3) has opened up a new line of investigation for interaction between recall responses and host chemokines to activate immune responses against a separate antigen, and 4) provides future prospects of utilizing chemokines as adjuvants for additional immunotherapies targeting aggressive tumors. Together, these studies hold great promise to improve the responses in patients with GBM.</p> / Dissertation
55

Unexpected Ovarian Malignancy Found after Laparoscopic Surgery in Patients with Adnexal Masses : A Single Institutional Experience

OKAMOTO, TOMOMITSU, TANAKA, SHIHO, KIKKAWA, FUMITAKA, MIZUNO, MIKA, MIWA, YOKO, KAJIYAMA, HIROAKI, SAITO, SHIGEKO 02 1900 (has links)
No description available.
56

Vital role of HERV-K in malignant disease progression provides a novel target for cancer therapeutics

Ho, Catherine Ngoc 24 October 2018 (has links)
Human Endogenous Retroviruses (HERV) are segments of the human genome that are viral in origin and occupy approximately 8% of the human genome, which is nearly 3 times as much as functional protein coding genes (3%). Although most are defective due to accumulation of post insertional mutations, Human Endogenous Retrovirus Type K (HERV-K) retains the ability to produce functional particles and is activated during progression of malignant disease. The resulting proviral products have been associated tumorigenesis through their presumed role in malignant cell production. While therapeutics that focus on HERV-K inhibition have not been manufactured, current Federal Drug Administration (FDA) approved antiretroviral therapies are capable of decreasing expression of HERV-K in cancer cells. In summary, antiretroviral drugs may serve as a promising new anticancer drug by targeting and decreasing expression of HERV-K proteins.
57

Perfil de expressão do receptor do peptídeo liberador de gastrina em materiais de biópsia de pacientes portadores de melanoma maligno

Marrone, Bianca Fontana January 2012 (has links)
Introdução: A incidência de melanoma maligno (MM) está aumentando mundialmente e o manejo de pacientes com doença avançada representa um difícil problema. Durante décadas, a quimioterapia foi o tratamento padrão no tratamento de pacientes com MM metastático. Entretanto, essa modalidade tem produzido resultados desapontadores. Recentemente, com os avanços no conhecimento sobre os eventos moleculares relacionados ao desenvolvimento do MM, novas drogas dirigidas a alvos moleculares de relevância na doença têm sido identificadas. O peptídeo liberador de gastrina (GRP) é um peptídeo neuroendócrino, o qual possui efeito estimulador no crescimento em vários tipos de neoplasias murinas e humanas. Poucos dados são conhecidos em relação à expressão de receptores de GRP (GRPR) em materiais de biópsia de pacientes portadores de MM. A identificação de uma expressão elevada destes receptores no MM poderá permitir uma maior compreensão sobre a biologia desta neoplasia, bem como embasar estudos com o uso de moduladores desta via de sinalização com potencial ação terapêutica. Objetivos: O objetivo desse estudo foi determinar a expressão de receptores de GRP em biópsias de pacientes com MM, bem como buscar eventuais correlações entre os níveis de expressão de GRPR e fatores prognósticos reconhecidos nesta doença. Métodos: Foi realizado um estudo imuno-histoquímico (IHQ) em blocos fixados em formalina e embebidos em parafina, contendo material de biópsia de 51 pacientes portadores de MM cutâneo. Utilizou-se um anticorpo policlonal de coelho anti-GRPR (OPA1-15619, Affinity Bioreagents, USA). Após a quantificação da expressão de GRPR nas amostras, foram analisadas as diferenças de expressão entre subgrupos prognósticos, com a aplicação do teste exato de Fisher. Resultados: A expressão de GRPR foi demonstrada no citoplasma de 42 das 51 (82,4%) amostras de MM cutâneo. A expressão foi considerada forte em 30 amostras (58,9%). Não foi observada diferença significativa na expressão de GRPR quando foram analisadas amostras de MM em sítio primário versus metastático. Foram correlacionados os escores da expressão de GRPR com os achados patológicos associados ao prognóstico do MM cutâneo primário, não tendo sido detectadas diferenças significativas com relação aos níveis de Clark (p=0,35) e Índice espessura de Breslow (p= 0,175). Conclusão: Nosso trabalho mostrou uma expressão de GRPR em amostras de MM cutâneo na vasta maioria dos casos (82,4%). Em 30 amostras (58.3%), a expressão de GRPR foi considerada de forte intensidade. Não houve associação entre a intensidade de expressão de GRPR quando comparadas amostras de sítio primário versus metastático, níveis de Clark ou índices de Breslow. Este estudo é um dos primeiros na literatura a descrever uma expressão de GRPR elevada em amostras obtidas de pacientes portadores de MM cutâneo. Estudos subsequentes, preferencialmente com um maior número amostral, são necessários para confirmar estes achados e permitir melhor análise da expressão deste receptor em distintos subgrupos prognósticos. Se confirmados, os nossos dados podem justificar a realização de estudos que explorem novas estratégias terapêuticas utilizando agentes moduladores da expressão de GRPR em pacientes com MM refratário ao tratamento convencional. / Background: The incidence of malignant melanoma (MM) is increasing worldwide and the management of patients with disseminated disease is a difficult problem. Chemotherapy was the treatment of choice in metastatic melanomas for many decades. However, this option produces disappointing results. Recently, the better understanding about molecular events related do the development of MM allowed the development of new drugs directed against specific molecular targets. The gastrin-releasing peptide (GRP) is a neuroendocrine peptide shown to have growth-stimulatory effects on many types of murine and human cancers. Few data are available about GRP receptor (GRPR) expression in MM. The understanding about the molecular biology of MM may allow the identification of novel intracellular pathways of relevance in this disease, and potential GRPR modulators of therapeutic application in patients with refractory MM. Objectives: The aim of this study was to determine the GRPR expression in biopsy samples of patients with cutaneous MM, as well as to correlate its expression with known prognostic factors of relevance in this disease. Methods: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsy samples from 51 patients with cutaneous MM. A rabbit polyclonal anti-GRPR antibody (OPA1-15619, Affinity Bioreagents, USA) was used. Following the quantification of GRPR expression in the samples, the differences in GRPR expression among distinct prognostic MM subgroups were analyzed, using the Fisher´s test. Results: GRPR immunoexpression was demonstrated in cytoplasm of 42/51 (82.4%) cutaneous MM cases. It was strongly expressed in 30 (58.9%) of the samples. No significant differences between GRPR expression neither in relation to the primary or metastatic site, nor among known prognostic subgroups Clark´s level (p=0.35) and Breslow index ( p= 0.175) was observed. Conclusion: Our study has demonstrated the occurrence of a high GRPR expression in tumor specimens obtained from patients with cutaneous MM (82,4%). In 30 samples, a strong intensity of expression was documented (58.3%). No correlation was observed between the level of GRPR expression in primary or metastatic sites, nor for distinct Clark´s levels or Breslow index. This is one of the first studies demonstrating a high GRPR expression in tumor samples from patients with MM. Further studies are warranted, preferably including a larger patient population, to allow a better analysis of the expression of these receptors in different prognostic subgroups. If these observations are confirmed, the therapeutic use of GRPR inhibitors should be considered in patients with advanced MM who failed conventional treatments.
58

Perfil de expressão do receptor do peptídeo liberador de gastrina em materiais de biópsia de pacientes portadores de melanoma maligno

Marrone, Bianca Fontana January 2012 (has links)
Introdução: A incidência de melanoma maligno (MM) está aumentando mundialmente e o manejo de pacientes com doença avançada representa um difícil problema. Durante décadas, a quimioterapia foi o tratamento padrão no tratamento de pacientes com MM metastático. Entretanto, essa modalidade tem produzido resultados desapontadores. Recentemente, com os avanços no conhecimento sobre os eventos moleculares relacionados ao desenvolvimento do MM, novas drogas dirigidas a alvos moleculares de relevância na doença têm sido identificadas. O peptídeo liberador de gastrina (GRP) é um peptídeo neuroendócrino, o qual possui efeito estimulador no crescimento em vários tipos de neoplasias murinas e humanas. Poucos dados são conhecidos em relação à expressão de receptores de GRP (GRPR) em materiais de biópsia de pacientes portadores de MM. A identificação de uma expressão elevada destes receptores no MM poderá permitir uma maior compreensão sobre a biologia desta neoplasia, bem como embasar estudos com o uso de moduladores desta via de sinalização com potencial ação terapêutica. Objetivos: O objetivo desse estudo foi determinar a expressão de receptores de GRP em biópsias de pacientes com MM, bem como buscar eventuais correlações entre os níveis de expressão de GRPR e fatores prognósticos reconhecidos nesta doença. Métodos: Foi realizado um estudo imuno-histoquímico (IHQ) em blocos fixados em formalina e embebidos em parafina, contendo material de biópsia de 51 pacientes portadores de MM cutâneo. Utilizou-se um anticorpo policlonal de coelho anti-GRPR (OPA1-15619, Affinity Bioreagents, USA). Após a quantificação da expressão de GRPR nas amostras, foram analisadas as diferenças de expressão entre subgrupos prognósticos, com a aplicação do teste exato de Fisher. Resultados: A expressão de GRPR foi demonstrada no citoplasma de 42 das 51 (82,4%) amostras de MM cutâneo. A expressão foi considerada forte em 30 amostras (58,9%). Não foi observada diferença significativa na expressão de GRPR quando foram analisadas amostras de MM em sítio primário versus metastático. Foram correlacionados os escores da expressão de GRPR com os achados patológicos associados ao prognóstico do MM cutâneo primário, não tendo sido detectadas diferenças significativas com relação aos níveis de Clark (p=0,35) e Índice espessura de Breslow (p= 0,175). Conclusão: Nosso trabalho mostrou uma expressão de GRPR em amostras de MM cutâneo na vasta maioria dos casos (82,4%). Em 30 amostras (58.3%), a expressão de GRPR foi considerada de forte intensidade. Não houve associação entre a intensidade de expressão de GRPR quando comparadas amostras de sítio primário versus metastático, níveis de Clark ou índices de Breslow. Este estudo é um dos primeiros na literatura a descrever uma expressão de GRPR elevada em amostras obtidas de pacientes portadores de MM cutâneo. Estudos subsequentes, preferencialmente com um maior número amostral, são necessários para confirmar estes achados e permitir melhor análise da expressão deste receptor em distintos subgrupos prognósticos. Se confirmados, os nossos dados podem justificar a realização de estudos que explorem novas estratégias terapêuticas utilizando agentes moduladores da expressão de GRPR em pacientes com MM refratário ao tratamento convencional. / Background: The incidence of malignant melanoma (MM) is increasing worldwide and the management of patients with disseminated disease is a difficult problem. Chemotherapy was the treatment of choice in metastatic melanomas for many decades. However, this option produces disappointing results. Recently, the better understanding about molecular events related do the development of MM allowed the development of new drugs directed against specific molecular targets. The gastrin-releasing peptide (GRP) is a neuroendocrine peptide shown to have growth-stimulatory effects on many types of murine and human cancers. Few data are available about GRP receptor (GRPR) expression in MM. The understanding about the molecular biology of MM may allow the identification of novel intracellular pathways of relevance in this disease, and potential GRPR modulators of therapeutic application in patients with refractory MM. Objectives: The aim of this study was to determine the GRPR expression in biopsy samples of patients with cutaneous MM, as well as to correlate its expression with known prognostic factors of relevance in this disease. Methods: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsy samples from 51 patients with cutaneous MM. A rabbit polyclonal anti-GRPR antibody (OPA1-15619, Affinity Bioreagents, USA) was used. Following the quantification of GRPR expression in the samples, the differences in GRPR expression among distinct prognostic MM subgroups were analyzed, using the Fisher´s test. Results: GRPR immunoexpression was demonstrated in cytoplasm of 42/51 (82.4%) cutaneous MM cases. It was strongly expressed in 30 (58.9%) of the samples. No significant differences between GRPR expression neither in relation to the primary or metastatic site, nor among known prognostic subgroups Clark´s level (p=0.35) and Breslow index ( p= 0.175) was observed. Conclusion: Our study has demonstrated the occurrence of a high GRPR expression in tumor specimens obtained from patients with cutaneous MM (82,4%). In 30 samples, a strong intensity of expression was documented (58.3%). No correlation was observed between the level of GRPR expression in primary or metastatic sites, nor for distinct Clark´s levels or Breslow index. This is one of the first studies demonstrating a high GRPR expression in tumor samples from patients with MM. Further studies are warranted, preferably including a larger patient population, to allow a better analysis of the expression of these receptors in different prognostic subgroups. If these observations are confirmed, the therapeutic use of GRPR inhibitors should be considered in patients with advanced MM who failed conventional treatments.
59

"Correlação entre os aspectos clínicos e a tomografia computadorizada na avaliação da destruição óssea provocada por neoplasias malignas de boca e orofaringe" / Clinical and computed tomography correlation in the assessment of bone invasion in oral and oropharynx malignant neoplasms

Marco Antonio Portela Albuquerque 15 October 2004 (has links)
A avaliação da presença de destruição óssea provocada por neoplasias malignas de boca e orofaringe é um fator de fundamental importância no estabelecimento da terapêutica adequada para o caso, como também, para a determinação do prognóstico do paciente. O presente estudo teve por objetivo determinar os aspectos clínicos (localização, forma de apresentação e estadiamento) que podem estar associadas com o potencial de infiltração do osso subjacente a lesão, como também determinar a sensibilidade e especificidade do exame físico. A população de estudo consistio de vinte e cinco pacientes (17 homens e 8 mulheres, média de idade de 57,88 anos) portadores de neoplasias malignas de boca e orofaringe atendidos no Ambulatório de Semiologia da Faculdade de Odontologia da Universidade de São Paulo – campus São Paulo, no período de agosto de 2003 a agosto de 2004, os quais foram submetidos ao exame clínico e a tomografia computadorizada (TC). A TC foi considerada o padrão ouro para a avaliação da presença de destruição óssea. Foi observada a presença de infiltração neoplásica para o tecido ósseo adjacente em 68% dos casos (17 pacientes). O exame físico dos pacientes revelou uma sensibilidade de 80% e especificidade de 87,50% na análise de comprometimento do osso, além de uma acurácia de 84%. As lesões que se apresentavam clinicamente como uma úlcera do tipo infiltrativa e lesões do tipo nodulares, não ulceradas, foram as que apresentaram maior potencial de infiltrar-se para o osso, 68,75% e 100% respectivamente. A localização do tumor em determinados sítios, também influenciou diretamente na presença de invasão óssea,principalmente lesões localizadas em região de gengiva, trígono retromolar, palato duro e orofaringe. O estadiamento das lesões revelou relação existente entre o tamanho do tumor e a presença de metástases à distância com a presença de infiltração da neoplasia para o tecido ósseo. Concluindo, observou-se que a identificação de determinados parâmetros clínicos como localização, forma de apresentação clinica, tamanho da lesão e a presença de metástases à distância, associado a um criterioso exame físico regional podem servir como valiosas ferramentas para a análise de envolvimento ósseo por neoplasias malignas de boca e orofaringe. / The assessment of bone destruction by oral and oropharynx malignant neoplasms is a critical factor in the therapeutic planning and to determine the patient prognostic. The aim of this study was to determine the clinical aspects (localization, clinical manifestation and stage) that can be associated with the potential of bone infiltration, and also determine the physical exam sensibility and specificity. The study population consisted of twenty five patients (17 men and 8 women, mean age 57.88 years-old), with malignant neoplasms of the mouth and oropharynx, of the Stomatology Clinic of the College of Dentistry at the Sao Paulo University - campus Sao Paulo, in the period of august 2003 to august 2004, who were submitted to a clinical and computed tomography (CT) examinations. CT was considered the gold standard to evaluate the presence of bone involvement. The presence of bone destruction by the tumor was observed in 68% of the cases (17 patients). The physical examination of the patients revealed 82% of sensibility, 87.50% of specificity, and 84% of accuracy in the assessment of bone invasion by these diseases. The lesions that were clinical considered to be infiltrative ulcer and nodular lesions, non-ulcerated, presented the highest potential to cause bone destruction, 68.75% and 100% respectively. The tumor localization in specific sites also influenced the presence of bone invasion, meanly with the lesions localized in the gingival, retromolar trigone, hard palate and oropharynx. The stage of the lesions revealed a relation between the size and the presence of distant metastasis, with the presence of invasion by the neoplasm. In conclusion, it was determined that the identification of some clinical parameters such localization, clinical presentation, lesion size and the presence of distant metastasis, associated with a perceptive regional physical exam must be use as a value tool is the assessment of bone destruction by oral and oropharynx malignant neoplasms.
60

Perfil de expressão do receptor do peptídeo liberador de gastrina em materiais de biópsia de pacientes portadores de melanoma maligno

Marrone, Bianca Fontana January 2012 (has links)
Introdução: A incidência de melanoma maligno (MM) está aumentando mundialmente e o manejo de pacientes com doença avançada representa um difícil problema. Durante décadas, a quimioterapia foi o tratamento padrão no tratamento de pacientes com MM metastático. Entretanto, essa modalidade tem produzido resultados desapontadores. Recentemente, com os avanços no conhecimento sobre os eventos moleculares relacionados ao desenvolvimento do MM, novas drogas dirigidas a alvos moleculares de relevância na doença têm sido identificadas. O peptídeo liberador de gastrina (GRP) é um peptídeo neuroendócrino, o qual possui efeito estimulador no crescimento em vários tipos de neoplasias murinas e humanas. Poucos dados são conhecidos em relação à expressão de receptores de GRP (GRPR) em materiais de biópsia de pacientes portadores de MM. A identificação de uma expressão elevada destes receptores no MM poderá permitir uma maior compreensão sobre a biologia desta neoplasia, bem como embasar estudos com o uso de moduladores desta via de sinalização com potencial ação terapêutica. Objetivos: O objetivo desse estudo foi determinar a expressão de receptores de GRP em biópsias de pacientes com MM, bem como buscar eventuais correlações entre os níveis de expressão de GRPR e fatores prognósticos reconhecidos nesta doença. Métodos: Foi realizado um estudo imuno-histoquímico (IHQ) em blocos fixados em formalina e embebidos em parafina, contendo material de biópsia de 51 pacientes portadores de MM cutâneo. Utilizou-se um anticorpo policlonal de coelho anti-GRPR (OPA1-15619, Affinity Bioreagents, USA). Após a quantificação da expressão de GRPR nas amostras, foram analisadas as diferenças de expressão entre subgrupos prognósticos, com a aplicação do teste exato de Fisher. Resultados: A expressão de GRPR foi demonstrada no citoplasma de 42 das 51 (82,4%) amostras de MM cutâneo. A expressão foi considerada forte em 30 amostras (58,9%). Não foi observada diferença significativa na expressão de GRPR quando foram analisadas amostras de MM em sítio primário versus metastático. Foram correlacionados os escores da expressão de GRPR com os achados patológicos associados ao prognóstico do MM cutâneo primário, não tendo sido detectadas diferenças significativas com relação aos níveis de Clark (p=0,35) e Índice espessura de Breslow (p= 0,175). Conclusão: Nosso trabalho mostrou uma expressão de GRPR em amostras de MM cutâneo na vasta maioria dos casos (82,4%). Em 30 amostras (58.3%), a expressão de GRPR foi considerada de forte intensidade. Não houve associação entre a intensidade de expressão de GRPR quando comparadas amostras de sítio primário versus metastático, níveis de Clark ou índices de Breslow. Este estudo é um dos primeiros na literatura a descrever uma expressão de GRPR elevada em amostras obtidas de pacientes portadores de MM cutâneo. Estudos subsequentes, preferencialmente com um maior número amostral, são necessários para confirmar estes achados e permitir melhor análise da expressão deste receptor em distintos subgrupos prognósticos. Se confirmados, os nossos dados podem justificar a realização de estudos que explorem novas estratégias terapêuticas utilizando agentes moduladores da expressão de GRPR em pacientes com MM refratário ao tratamento convencional. / Background: The incidence of malignant melanoma (MM) is increasing worldwide and the management of patients with disseminated disease is a difficult problem. Chemotherapy was the treatment of choice in metastatic melanomas for many decades. However, this option produces disappointing results. Recently, the better understanding about molecular events related do the development of MM allowed the development of new drugs directed against specific molecular targets. The gastrin-releasing peptide (GRP) is a neuroendocrine peptide shown to have growth-stimulatory effects on many types of murine and human cancers. Few data are available about GRP receptor (GRPR) expression in MM. The understanding about the molecular biology of MM may allow the identification of novel intracellular pathways of relevance in this disease, and potential GRPR modulators of therapeutic application in patients with refractory MM. Objectives: The aim of this study was to determine the GRPR expression in biopsy samples of patients with cutaneous MM, as well as to correlate its expression with known prognostic factors of relevance in this disease. Methods: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsy samples from 51 patients with cutaneous MM. A rabbit polyclonal anti-GRPR antibody (OPA1-15619, Affinity Bioreagents, USA) was used. Following the quantification of GRPR expression in the samples, the differences in GRPR expression among distinct prognostic MM subgroups were analyzed, using the Fisher´s test. Results: GRPR immunoexpression was demonstrated in cytoplasm of 42/51 (82.4%) cutaneous MM cases. It was strongly expressed in 30 (58.9%) of the samples. No significant differences between GRPR expression neither in relation to the primary or metastatic site, nor among known prognostic subgroups Clark´s level (p=0.35) and Breslow index ( p= 0.175) was observed. Conclusion: Our study has demonstrated the occurrence of a high GRPR expression in tumor specimens obtained from patients with cutaneous MM (82,4%). In 30 samples, a strong intensity of expression was documented (58.3%). No correlation was observed between the level of GRPR expression in primary or metastatic sites, nor for distinct Clark´s levels or Breslow index. This is one of the first studies demonstrating a high GRPR expression in tumor samples from patients with MM. Further studies are warranted, preferably including a larger patient population, to allow a better analysis of the expression of these receptors in different prognostic subgroups. If these observations are confirmed, the therapeutic use of GRPR inhibitors should be considered in patients with advanced MM who failed conventional treatments.

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