RESUMO
AIMS: Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches. Thus, the need of integrative and comparative studies still persists. MATERIALS AND METHODS: In this study we tested and compared the effects of three different cannabinoid receptor agonists-anandamide (AEA), (R)-(+)-methanandamide (Meth-AEA) and CP 55,940 (CP)- on gastric cancer cell morphology, viability and death events in order to provide new insights to the use of these agents for therapeutic purposes. KEY FINDINGS: The three agents tested exhibited similar concentration-dependent effects in the induction of changes in cell morphology and cell loss, as well as in the decrease of cell viability and DNA laddering in the human gastric adenocarcinoma cell line (AGS). Differences among the cannabinoids tested were mostly observed in the density of cells found in early and late apoptosis and necrosis, favoring AEA and CP as the more effective inducers of apoptotic mechanisms, and Meth-AEA as a more effective inducer of necrosis through transient and rapid apoptosis. SIGNIFICANCE: Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.
Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , HumanosRESUMO
Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy.
Assuntos
Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Pesquisa Translacional Biomédica , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , MutaçãoRESUMO
Cannabinoid receptor (CBs) agonists affect the growth of tumor cells via activation of deadly cascades. The spectrum of action of these agents and the precise role of the endocannabinoid system (ECS) on oncogenic processes remain elusive. Herein we compared the effects of synthetic (CP 55-940 and WIN 55,212-2) and endogenous (anandamide or AEA) CBs agonists (10-20 µM) on morphological changes, cell viability, and induction of apoptosis in primary astrocytes and in two glioblastoma cell lines (C6 and U373 cells) in order to characterize their possible differential actions on brain tumor cells. None of the CBs agonist tested induced changes in cell viability or morphology in primary astrocytes. In contrast, CP 55-940 significantly decreased cell viability in C6 and U373 cells at 5 days of treatment, whereas AEA and WIN 55,212-2 moderately decreased cell viability in both cell lines. Treatment of U373 and C6 for 3 and 5 days with AEA or WIN 55,212-2 produced discrete morphological changes in cell bodies, whereas the exposure to CP 55-940 induced soma degradation. CP 55-940 also induced apoptosis in both C6 and U373 cell lines. Our results support a more effective action of CP 55-940 to produce cell death of both cell lines through apoptotic mechanisms. Comparative aspects between cannabinoids with different profiles are necessary for the design of potential treatments against glial tumors.
Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ácidos Araquidônicos/farmacologia , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Benzoxazinas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cicloexanóis/farmacologia , DNA , Endocanabinoides/farmacologia , Humanos , Morfolinas/farmacologia , Naftalenos/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Ratos , Ratos WistarRESUMO
In Mexico, there have been few studies on primary oral and sinonasal melanoma, an aggressive neoplasm with a low survival rate and few therapeutic alternatives. Further, there is limited information about its clinical and histopathological characteristics. The aim of this retrospective study was to describe the clinicopathological profile of these tumours in patients attending a major oncology reference centre in Mexico City over a 12-year period. Demographic and clinical data were obtained from the clinical charts, and histopathological features were evaluated. χ(2), Fisher's exact, and Mann-Whitney U-tests were used for analysis; significance was set at P<0.05. Thirty-three cases were studied (73% sinonasal melanoma (SNM) and 27% oral melanoma (OM)); 58% were female and the median age was 66 (Q1-Q3 55.5-75) years. Compared with OM patients, SNM patients had a shorter time to diagnosis (16.7 vs. 11.7 months, P=0.022), were identified at earlier stages (33.3% vs. 58.3%, P=0.010), and all presented symptoms (66.7% vs. 100%, P=0.015). All samples showed vertical growth and 96.9% exhibited pleomorphism. A higher proportion of cases with pleomorphism developed metastases at follow-up than those without (60% vs. 12.5%, P=0.026). The present study provides valuable information that could form the basis of future studies in the search for advanced therapy modalities.
Assuntos
Melanoma/patologia , Neoplasias Bucais/patologia , Neoplasias dos Seios Paranasais/patologia , Idoso , Demografia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/epidemiologia , Melanoma/terapia , México/epidemiologia , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/terapia , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Several studies have shown the participation of MMPs in oral squamous cell carcinoma, the most frequent malignant neoplasm of the oral cavity. The expression of some MMPs correlates with a more aggressive biological behaviour. The objective of this study was to determine which MMPs and TIMPs were expressed in both neoplastic and peritumoural stromal cells in different histopathology areas. METHODS: Patients who underwent primary tumour neck dissection for oral squamous cell carcinoma were included. Immunoexpression of MMP-1, -2, -3, -7, -9, -11, -13, and TIMP-1 and -2 in different areas of pathologic specimens (in situ carcinoma, primary tumour, invasive front, distant invasion carcinoma, and lymph node metastasis) was evaluated. Enzyme expression on mucosa adjacent to tumour served as control. RESULTS: Thirty cases were included. Only 6 MMPs and 1 TIMP were expressed in the studied areas. Statistically significant differences in the number of cases with positive MMPs or TIMP expression, in both neoplastic and peritumoural cells, between control and the rest of the areas were observed. MMP-2 expression was constant in the areas with a more aggressive biological behaviour. CONCLUSIONS: MMP-2 expression may represent a dynamic interaction between host and tumour that favours the establishment of neoplastic cells at distant sites.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Metaloproteinases da Matriz/metabolismo , Neoplasias Bucais/enzimologia , Células-Tronco Neoplásicas/enzimologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , PrognósticoRESUMO
The purpose of this study was to analyze the prognostic and predictive factors that relate to locoregional or distant recurrences in breast cancer patients who have been treated at the National Cancer Institute of Mexico. Multivariate, time-dependent Cox regression analyses indicate that the pN status (positive versus negative lymph node; P = 0.003; HR (hazard ratio), 3.47; CI (confidence interval), 1.52-7.91) and the pathological complete response of the patient to neoadjuvant chemotherapy (yes versus no; P = 0.061; HR, 0.38; CI, 0.14-1.04) were important prognostic factors for recurrence.
RESUMO
A tumor bank (TB) is an ordered collection of neoplastic samples, normal tissue, and/or fluids preserved under optimal conditions, as well as storing patients' clinical information. The objective of this article is to outline the planning and logistics necessary for the functioning of the Instituto Nacional de Cancerología (INCan) TB in Mexico City. For the planning and logistics of a TB, several technical, legal, medical, structural, and physical aspects were considered, which can be grouped under four headings: (1) design and structure, (2) equipping the area and informatics, (3) ethical-legal aspects, and (4) sample collection, preservation, and quality control. One crucial element of interinstitutional interest will be the transfer of these concepts to the different oncological centers, integrating in this manner a network that enables the exploration of the different pathologies from therapeutic, epidemiological, and molecular points of view.
Assuntos
Academias e Institutos/organização & administração , Neoplasias/patologia , Manejo de Espécimes/normas , Bancos de Tecidos/organização & administração , Academias e Institutos/economia , Academias e Institutos/legislação & jurisprudência , Academias e Institutos/normas , Confidencialidade , Arquitetura de Instituições de Saúde , Humanos , Consentimento Livre e Esclarecido , Propriedade Intelectual , México , Objetivos Organizacionais , Desenvolvimento de Programas , Controle de Qualidade , Bancos de Tecidos/economia , Bancos de Tecidos/legislação & jurisprudência , Bancos de Tecidos/normasRESUMO
The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a good start to determine the level of participation of air pollution in the development of lung cancer.
Assuntos
Neoplasias Pulmonares/mortalidade , Idoso , Feminino , Geografia , Humanos , Masculino , México/epidemiologia , Caracteres SexuaisRESUMO
Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature.
Assuntos
Neoplasias da Mama , Neoplasias Labiais/secundário , Tumor Filoide , Neoplasias da Língua/secundário , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lábio/patologia , Neoplasias Labiais/diagnóstico , Neoplasias Labiais/mortalidade , Neoplasias Labiais/patologia , Mastectomia Radical Modificada , Mastectomia Segmentar , Pessoa de Meia-Idade , Metástase Neoplásica , Tumor Filoide/diagnóstico , Tumor Filoide/tratamento farmacológico , Tumor Filoide/mortalidade , Tumor Filoide/patologia , Tumor Filoide/secundário , Tumor Filoide/cirurgia , Língua/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologiaRESUMO
AIM: To classify 163 ameloblastoma cases according to the new WHO Classification of Odontogenic Tumours (2005) and analyse their clinical and microscopic features. METHODS: We studied the clinico-pathological features of 163 ameloblastoma cases from nine regional Latin-American institutions from Mexico and Guatemala. RESULTS: Ameloblastomas comprised 22.7% of all odontogenic tumours. The mean age was 41.4 years for solid ameloblastoma (SA) and 26.3 years for unicystic ameloblastoma (UA) (P < 0.001) and both sexes were almost equally affected. The mandible was mainly affected for both UA and SA. The mean size was 6.2 cm for SA and 6.3 cm for UA cases. The recurrence rate was 21.7% for SA and 12.6% for UA. UA was twice as more frequent than the solid variant. CONCLUSIONS: In this study we found that UA was frequently misdiagnosed as SA; however, there are enough clinical and microscopic features that allow for an accurate differentiation between both types of ameloblastoma that should be recognized for surgical and prognostic purposes. In this study, SA was not found in patients younger than 20 years, UA had a constant myxoid stroma while mature connective tissue was more frequently associated with the solid type.