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1.
Braz. j. biol ; 79(2): 311-320, Apr.-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989459

RESUMO

Abstract The present paper addresses the feeding activity of Trachinotus cayennensis, collected in Lençóis Bay (1°18'S - 1°19'S; 44°51'W - 44°53'W) on the western coast of the state of Maranhão, Brazil. Sampling was conducted between June 2012 and June 2013 using driftnets with stretch mesh sizes from 95 to 100 mm. A total of 205 individuals (114 females and 91 males) were analyzed. Statistically significant differences in the sex ratio were found in June, September and December 2012. Food items were analyzed based on frequency of occurrence and volumetric method, with the subsequent calculation of the alimentary importance index. Three size groups were defined to determine possible ontogenetic changes in eating habits based on the size range of the individuals collected: I (˂ 29 cm), II (29.1 to 37.0) and III (≥ 37.1). Eleven food item categories were identified: mollusks, polychaetes, crustaceans, nematodes, insects, algae, bryozoans, ophiuroids, fishes, vegetal matter and sediments. The variety of items in the diet of T. cayennensis indicates considerable feeding plasticity and opportunistic behavior. Seasonal variations influenced the feeding pattern of the species, with greater feeding activity in the dry season. The considerable availability of resources in estuarine habitats of the western coast of Maranhão constitutes another factor that influences the feeding behavior of this species.


Resumo Atividade alimentar do pampo Trachinotus cayennensis (Cuvier 1832) (Perciformes, Carangidae) em estuários na costa ocidental do Maranhão, Brasil. O presente trabalho descreve a atividade alimentar do Trachinotus cayennensis , coletado na Baía de Lençóis (1°18'S - 1°19'S; 44°51'W - 44°53'W) na costa oeste do Maranhão. Amostragens foram realizadas entre junho de 2012 e junho de 2013, utilizando redes de emalhar à deriva com tamanho de malha de 95 a 100 mm. Foram analisados ​​205 indivíduos (114 fêmeas e 91 machos). Encontraram-se diferenças estatisticamente significativas na proporção sexual nos meses de junho, setembro e dezembro de 2012. Os itens alimentares foram analisados ​​com base na frequência de ocorrência e utilizando o método volumétrico, com o subsequente cálculo do índice de importância alimentar. Três grupos de tamanho foram definidos para determinar possíveis mudanças ontogenéticas nos hábitos alimentares com base na faixa de tamanho dos indivíduos coletados: I (˂ 29 cm), II (29,1 a 37,0) e III (≥ 37,1). Foram identificadas 11 categorias de alimentos: moluscos, poliquetas, crustáceos, nematoides, insetos, algas, briozoários, ophiuro, peixes, matéria vegetal e sedimentos. A variedade de itens na dieta de T. cayennensis indica uma plasticidade alimentar considerável e um comportamento oportunista. As variações sazonais influenciaram o padrão alimentar da espécie, com maior atividade de alimentação na estação seca. A considerável disponibilidade de recursos nos habitats estuarinos da costa oeste do Maranhão constitui outro fator que exerce influência sobre o comportamento alimentar desta espécie.


Assuntos
Animais , Masculino , Feminino , Perciformes/fisiologia , Comportamento Alimentar/fisiologia , Brasil , Estuários
2.
Endocr Relat Cancer ; 26(3): 355-366, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30645190

RESUMO

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.


Assuntos
Craniofaringioma/fisiopatologia , Proteínas Hedgehog/antagonistas & inibidores , Adolescente , Animais , Proliferação de Células , Criança , Pré-Escolar , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Neoplasias Hipofisárias , Transdução de Sinais
3.
Genes Immun ; 18(2): 67-74, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28123183

RESUMO

Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in interleukin-6 (IL-6; P<0.005), but not tumor necrosis factor-α (TNF-α), secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.


Assuntos
Poeira , Epistasia Genética , Receptor 10 Toll-Like/genética , Receptor 1 Toll-Like/genética , Receptor 6 Toll-Like/genética , Idoso , Criação de Animais Domésticos , Animais , Feminino , Humanos , Imunidade Inata , Interleucina-6/imunologia , Lipopeptídeos/imunologia , Lipopeptídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Peptidoglicano/imunologia , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Suínos , Receptor 1 Toll-Like/imunologia , Receptor 10 Toll-Like/imunologia , Receptor 6 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/imunologia
4.
Oncogene ; 36(22): 3104-3118, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28068324

RESUMO

Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.


Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Proteínas dos Microfilamentos/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Neoplasias Colorretais/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Nus , Proteínas dos Microfilamentos/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-akt/genética
5.
Aust Dent J ; 62(2): 192-199, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27861968

RESUMO

BACKGROUND: Caries prevention is paramount in safeguarding the life quality of head and neck cancer patients and is dependent on patient compliance with caries preventive protocols. The purpose of this study was to examine this compliance. METHODS: All records of patients referred to one public oral medicine clinic servicing a head and neck oncology unit of one major Western Australian hospital, between January 2005 and December 2011, were examined. Data extracted included patient and cancer characteristics and compliance with dietary advice, dental care, oral hygiene instruction and fluoride use over a follow-up period of at least 12 months. Compliance was assessed against various oral health outcomes and patient characteristics. RESULTS: Of the 116 participants, 75.9% complied with all caries preventive measures over a mean follow-up period of 45 months. Non-compliance with regular dental attendance (P = 0.004), oral hygiene instruction (P = 0.009), dietary advice (P = 0.034) and daily fluoride use (P = 0.018) were associated with the development of dental caries post-treatment. The presence of dental caries at the time of cancer diagnosis was predictive of poorer compliance. CONCLUSIONS: High compliance with caries preventive measures is attainable in the head and neck cancer patient group. Factors other than fluoride use seem important in caries prevention.


Assuntos
Assistência Odontológica/métodos , Cárie Dentária/complicações , Cárie Dentária/prevenção & controle , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Cooperação do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Cárie Dentária/psicologia , Feminino , Fluoretos/uso terapêutico , Seguimentos , Neoplasias de Cabeça e Pescoço/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Fosfatos/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Oncogene ; 35(20): 2645-54, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-26364605

RESUMO

MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model.


Assuntos
Colite/complicações , Colite/metabolismo , Neoplasias Colorretais/complicações , Mucina-4/deficiência , Mucina-4/genética , Animais , Complexo CD3/metabolismo , Colite/genética , Colite/imunologia , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Histiócitos/imunologia , Histiócitos/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Linfócitos T/metabolismo
7.
Oncogene ; 34(16): 2052-60, 2015 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24909166

RESUMO

Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically engineered mouse model (LSL-K-ras(G12D)) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-ras(G12D); Pdx-1cre) and their control unfloxed (LSL-K-ras(G12D)) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m(3)) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The systemic accumulation of myeloid-derived suppressor cells (MDSCs) decreased significantly in floxed mice compared with unfloxed controls (P<0.01) after the smoke exposure with the concurrent increase in the macrophage (P<0.05) and dendritic cell (DCs) (P<0.01) population. Further, smoking-induced inflammation (IFN-γ, CXCL2; P<0.05) was accompanied by enhanced activation of pancreatic stellate cells and elevated levels of serum retinoic acid-binding protein 4, indicating increased bioavailability of retinoic acid which contributes to differentiation of MDSCs to tumor-associated macrophages (TAMs) and DCs. TAMs predominantly contribute to the increased expression of heparin-binding epidermal growth factor-like growth factor (EGFR ligand) in pre-neoplastic lesions in smoke-exposed floxed mice that facilitate acinar-to-ductal metaplasia (ADM). Further, smoke exposure also resulted in partial suppression of the immune system early during PC progression. Overall, the present study provides a novel mechanism of smoking-induced increase in ADM in the presence of constitutively active K-ras mutation.


Assuntos
Carcinoma in Situ/patologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/biossíntese , Macrófagos/citologia , Células Mieloides/citologia , Neoplasias Pancreáticas/patologia , Fumar/efeitos adversos , Células Acinares/patologia , Animais , Carcinoma Ductal Pancreático/patologia , Diferenciação Celular/genética , Quimiocina CXCL2/biossíntese , Células Dendríticas/citologia , Progressão da Doença , Genes ras/genética , Inflamação/induzido quimicamente , Interferon gama/biossíntese , Queratina-19/biossíntese , Macrófagos/metabolismo , Metaplasia/induzido quimicamente , Camundongos , Camundongos Transgênicos , Ductos Pancreáticos/patologia , Células Estreladas do Pâncreas/metabolismo , Receptores do Ácido Retinoico/metabolismo , Transdução de Sinais/genética , Fumaça/efeitos adversos , Tretinoína/metabolismo
8.
Open Dent J ; 8: 168-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25328552

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) is the most common type of malignancy affecting the oral cavity. While exposures to main risk factors for oral SCC such as smoking and alcohol use are higher amongst the Aboriginal people, little is known about oral cancer in this population. This study aimed to describe characteristics and survival of oral SCC in Aboriginal and non-Aboriginal Western Australians. METHODS: All primary oral SCC cases reported to the Western Australian Cancer Registry (WACR) between 1990 and 1999 were analysed with respect to person characteristics including: date of birth, sex and indigenous status; and disease characteristics including: date of biopsy, disease stage and site as well as date of recurrence and date of death. Exclusion criteria included diagnosis not based on incisional or excisional biopsy, diagnosis other than oral SCC or a history of another malignant neoplasm. RESULTS: Aboriginal individuals were more likely to reside in rural areas. No statistically significant differences in oral SCC characteristics and survival were noted between Aboriginal and non-Aboriginal Western Australians. CONCLUSION: This study provides new information on person and disease characteristics of Aboriginal Western Australians diagnosed with oral SCC.

9.
Am J Transplant ; 12(11): 3069-75, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22883417

RESUMO

Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains problematic. A phase II trial adding rituximab to a low-dose cyclophosphamide and prednisone regimen was conducted for pediatric patients with Epstein-Barr virus (EBV) (+), CD20 (+) PTLD. Fifty-five patients were enrolled. Toxicity was similar for cycles of therapy containing rituximab versus those without. The complete remission (CR) rate was 69% (95% confidence interval (CI); 57%-84%). Of 12 patients with radiographic evidence of persistent disease at the end of therapy, eight were in CR 28 weeks later without further PTLD therapy. There were 10 deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2-year event-free survival (alive with functioning original allograft and no PTLD) was 71% (95% CI: 57%-82%) and overall survival was 83% (95% CI: 69%-91%) with median follow-up of 4.8 years. Due to small numbers, we were unable to determine significance of tumor histology, stage of disease, allograft type or early response to treatment on outcome. These data suggest rituximab combined with low-dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD following solid-organ transplantation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transtornos Linfoproliferativos/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Adolescente , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Intervalos de Confiança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Seguimentos , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Masculino , Dose Máxima Tolerável , Transplante de Órgãos/métodos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Medição de Risco , Rituximab , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
10.
Aust Dent J ; 56(3): 278-83, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21884143

RESUMO

BACKGROUND: Dentists have recently seen the introduction of devices which aim to facilitate early oral cancer detection, sparking interest in opportunistic oral cancer screening. However, concerns have been raised about the lack of regular dental attendance amongst high risk individuals. The purpose of this study was to obtain information pertaining to dental attendance of oral and oropharyngeal cancer patients. METHODS: All records of patients referred to the Oral Medicine Clinic at the Oral Health Centre of Western Australia, between January 2005 and December 2009, from one major teaching hospital were examined. Information extracted included age, gender, smoking status, referral date, tumour type, tumour site, disease stage (TNM classification), and information on dental attendance. Outcomes measured included time (months) since the patient's last dental visit and information concerning regularity of dental attendance. RESULTS: No association was found between dental attendance and gender, smoking, disease stage or age at diagnosis. Most patients had not visited a dentist in the preceding 12 months. The mean date of last dental visit was 5.6 years prior. CONCLUSIONS: More should be done in Australia to encourage patients at high risk of oral cancer to attend the dentist and undergo annual oral soft tissue examination.


Assuntos
Assistência Odontológica/estatística & dados numéricos , Neoplasias Bucais/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Unidade Hospitalar de Odontologia , Feminino , Neoplasias Gengivais/epidemiologia , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Fatores de Tempo , Neoplasias da Língua/epidemiologia , Neoplasias Tonsilares/epidemiologia , Austrália Ocidental/epidemiologia
11.
Br J Cancer ; 104(6): 1038-48, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21364589

RESUMO

BACKGROUND: Pancreatic cancer (PC) harbours an activated point mutation (Kras(G12D)) in the Kras proto-oncogene that has been demonstrated to promote the development of PC. METHODS: This study was designed to investigate the effect of the oncogenic Kras(G12D) allele on aggressiveness and metastatic potential of PC cells. We silenced the oncogenic Kras(G12D) allele expression in CD18/HPAF and ASPC1 cell lines by stable expression of shRNA specific to the Kras(G12D)allele. RESULTS: The Kras(G12D) knockdown cells exhibited a significant decrease in motility (P<0.0001), invasion (P<0.0001), anchorage-dependent (P<0.0001) and anchorage-independent growth (P<0.0001), proliferation (P<0.005) and an increase in cell doubling time (P<0.005) in vitro and a decrease in the incidence of metastases upon orthotopic implantation into nude mice. The knockdown of the Kras(G12D) allele led to a significant increase in the expression of E-cadherin (mRNA and protein) both in vitro and in vivo. This was associated with a decrease in the expression of phoshpo-ERK-1/2, NF-κB and MMP-9, and transcription factors such as δEF1, Snail and ETV4. Furthermore, the expression of several proteins involved in cell survival, invasion and metastasis was decreased in the Kras(G12D) knockdown cells. CONCLUSIONS: The results of this study suggest that the Kras(G12D) allele promotes metastasis in PC cells partly through the downregulation of E-cadherin.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Caderinas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/fisiologia , Animais , Ácido Aspártico/genética , Caderinas/fisiologia , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicina/genética , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Mutação Puntual , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , RNA Interferente Pequeno/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ras/metabolismo
12.
Aust Dent J ; 55(4): 378-84, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21174907

RESUMO

BACKGROUND: Biopsy of a suspected oral squamous cell carcinoma (SCC) is important for diagnosis. Concerns have been raised about the potential for tumour spread by incisional biopsy techniques. This study aimed to investigate the five-year survival and recurrence of oral SCC after incisional and excisional biopsy in total population data available from the Western Australian Cancer Registry (WACR). METHODS: Total population data from the WACR, comprising all primary oral SCC cases diagnosed between 1990 and 1999, were examined. Information extracted included date of birth, gender, biopsy date, biopsy type, disease stage (TNM classification), disease site, date of recurrence and date of death. Records were excluded if the diagnosis was fine needle aspiration based, was not that of oral SCC and if a history was noted of another malignant neoplasm. Incisional and excisional biopsy cases were compared for five-year survival, adjusting for disease stage. RESULTS: No association was found between biopsy type and five-year survival or recurrence amongst individuals with Stage I or II disease. CONCLUSIONS: In this study, biopsy type was not associated with survival of oral SCC patients with Stage I or II disease, adding to the evidence that incisional biopsy of oral SCC can be a safe procedure.


Assuntos
Biópsia/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Neoplasias Bucais/mortalidade , Inoculação de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Austrália Ocidental/epidemiologia
13.
Br J Cancer ; 103(5): 676-84, 2010 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-20664585

RESUMO

BACKGROUND: CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues. METHODS: We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75. RESULTS: We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo. CONCLUSION: Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.


Assuntos
Aminobenzoatos/administração & dosagem , Ligante CD27/imunologia , Imunoconjugados/uso terapêutico , Oligopeptídeos/administração & dosagem , Neoplasias Ovarianas/terapia , Neoplasias Pancreáticas/terapia , Animais , Anticorpos Monoclonais/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Nus
14.
Br J Cancer ; 99(1): 100-9, 2008 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-18542072

RESUMO

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in >or=50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC(50) values of 2-7 ng ml(-1). MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Neoplasias do Sistema Digestório/metabolismo , Glicoproteínas/antagonistas & inibidores , Peptídeos/antagonistas & inibidores , Antígeno AC133 , Antígenos CD/biossíntese , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neoplasias do Sistema Digestório/tratamento farmacológico , Glicoproteínas/biossíntese , Hepatócitos , Humanos , Hibridomas , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
15.
Aust Dent J ; 52(3): 205-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17969289

RESUMO

BACKGROUND: The aim of this study was to describe the demographic and health and lifestyle factors associated with dental service attendance in the previous 12 months by young Australian adults (18-24 years). METHODS: Population-based data from the 2001 Australian National Health Survey were analysed. Proportions and single associations between variables of interest and dental service attendance were calculated. A logistic regression analysis using significant single association variables was then conducted. RESULTS: Overall, 41 per cent of young adults in this study had visited a dental professional in the previous 12 months. Females, those in cities, those with private insurance, those who spoke languages other than English, those in the highest socioeconomic group and those with healthy behaviours were subgroups most likely to have visited a dental professional. With logistic regression, factors found to be associated with dental services attendance were being female, having private health insurance and low alcohol consumption. CONCLUSIONS: In this study, the proportion of young adults who had visited a dental professional in the previous 12 months was only 41 per cent. It is therefore suggested that oral health policy and promotion activities be encouraged for this group, paying attention to young adults in groups with low attendance.


Assuntos
Serviços de Saúde Bucal/estatística & dados numéricos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Análise de Variância , Austrália , Escolaridade , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Características de Residência , Fatores Sexuais , Fumar , Fatores Socioeconômicos
16.
Gynecol Oncol ; 103(2): 575-80, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16806439

RESUMO

OBJECTIVE: Previously, we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage müllerian malignancies. The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen that were predicted to reduce toxicity and possibly increase efficacy. METHODS: Open label two-cohort study. Patients with a new diagnosis of Stages II-IV müllerian malignancy were eligible. After cytoreductive surgery, patients were treated with three sequential doublets including 3 cycles of carboplatin and gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of doxorubicin and topotecan. After therapy, all women were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage IV (cohort 2), respectively. RESULTS: Eighty-five eligible patients were enrolled with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts 1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic toxicities were seen at a frequency of <10%. Seventy women underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2. CONCLUSIONS: Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias das Tubas Uterinas/tratamento farmacológico , Tumor Mulleriano Misto/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Topotecan/administração & dosagem , Topotecan/efeitos adversos , Gencitabina
17.
Ann Oncol ; 17(6): 920-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16524969

RESUMO

BACKGROUND: The aim of the study was to determine the outcome and clinical features predictive of survival in patients with follicular lymphoma (FL) treated aggressively and to determine the rate of disease-specific mortality in patients with grade 3 FL (FL3). MATERIALS AND METHODS: Four hundred and twenty-one patients with FL who were treated with various anthracycline-based chemotherapy regimens were included in this retrospective study. RESULTS: Patients with FL3 and a diffuse component of >50% had the worst outcome, with a hazard ratio of dying of 2.2 (95% CI 1.4-3.4) compared with patients with FL1 or FL2, and a ratio of 1.6 (95% CI 1.02-2.5) compared with FL3 with a diffuse component of < or =50% by multivariate analysis (P = 0.0026). Patients with FL3a had an outcome similar to those with FL3b. In patients with FL3 and a diffuse component of < or =50%, the overall and event-free survival curves showed a plateau for patients younger than 60 years of age. However, there were no differences in the cumulative incidence of relapse/progression or lymphoma-specific/treatment-related mortality between the two age groups. CONCLUSIONS: Less than half of the patients with FL3 and a diffuse component of < or =50% treated with anthracycline-based combination chemotherapy will relapse and relapses are uncommon after 6 years. Older patients should be offered the same aggressive chemotherapy as younger patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
18.
Child Care Health Dev ; 32(1): 111-9, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16398797

RESUMO

BACKGROUND: Child care workers play an important role in caring for children attending child care yet there is little research regarding their health. METHODS: The study consisted of focus groups with child care workers and a survey, conducted as part of a larger study known as the Healthy Child Care Study, which focused on children. The study investigated carers working in formal child care [long day care (LDC) and family day care (FDC)]. RESULTS: Questionnaires to caregivers in centres showed that 86% had taken sick leave in the previous year and 75% of staff had taken leave for infectious illness. Carers in FDC reported that 24% had taken sick leave in the previous year and 12% of carers had taken leave for infectious illness. Of responding caregivers from centres, 22% were cigarette smokers while in FDC homes, 8% of carers smoked. In focus groups, carers reported that their major areas of health concern were stress, infectious illness and physical trauma such as lifting injuries. CONCLUSIONS: Child care workers in LDC took more sick leave than those in FDC but this is not necessarily due to more illness. Child care workers are a diverse and important group that require further research.


Assuntos
Cuidadores , Cuidado da Criança , Creches , Doenças Profissionais/etiologia , Adolescente , Adulto , Cuidadores/psicologia , Pré-Escolar , Doenças Transmissíveis/etiologia , Feminino , Grupos Focais , Nível de Saúde , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , Licença Médica/estatística & dados numéricos , Estresse Psicológico/etiologia
19.
J Helminthol ; 78(4): 373-6, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15575998

RESUMO

Tissues from barred tiger salamanders (Ambystoma tigrinum mavortium), Great Plains toads (Bufo cognatus) and New Mexico spadefoots (Spea multiplicata) collected from 16 playa wetlands in Texas during 1999 and 2000 were examined by light microscopy. Digenean cysts were primarily distributed subcutaneously throughout the specimens and occasionally coelomic invasion was noted. The parasites within the cysts were 1.5-2 mm in diameter, with a thin (c. 10 microm wide) eosinophilic-staining tegument, two suckers (oral and ventral), posteriorly located primordial genitalia and paired digestive caeca. These digeneans were identified as the metacercariae of Clinostomum attenuatum. This is the first record of Clinostomum attenuatum in these amphibian species.


Assuntos
Ambystoma/parasitologia , Bufonidae/parasitologia , Ranidae/parasitologia , Trematódeos/crescimento & desenvolvimento , Animais , Estágios do Ciclo de Vida , Texas , Trematódeos/ultraestrutura
20.
Prev Med ; 37(5): 507-12, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14572435

RESUMO

BACKGROUND: It is estimated that approximately 50% of women in Australia with intellectual disability will live to 70 years of age and as a result many will fall within the age group at highest risk for breast cancer (50-69 years). METHODS: Subjects were identified through the Western Australia Disability Services database. To determine the number of women diagnosed with breast cancer during the period 1982-2000, individual records (n = 2,370) were linked to the Western Australia Cancer Registry and the Mammography Screening Registry. RESULTS: The incidence of breast cancer among women with intellectual disability was 64.0 per 100,000 person-years, by comparison with 146.7 per 100,000 person-years in the general population. The uptake of breast cancer screening was examined in a subgroup of 380 women, 34.7% of whom had used mammographic screening, as opposed to 54.6% screening uptake in the general population. Failure to use screening services was highest in women who were unmarried, and was positively associated with severity of intellectual disability, presence of physical disabilities, and urban residence. CONCLUSIONS: The lower incidence of breast cancer in women with intellectual disability may in part be attributable to decreased life expectancy, but it also appears to reflect significant under utilization of the readily available screening services.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Deficiência Intelectual , Mamografia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atividades Cotidianas , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Feminino , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Deficiência Intelectual/complicações , Deficiência Intelectual/psicologia , Expectativa de Vida , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Vigilância da População , Sistema de Registros , Características de Residência/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Pessoa Solteira/psicologia , Pessoa Solteira/estatística & dados numéricos , Saúde da População Urbana/estatística & dados numéricos , Austrália Ocidental/epidemiologia
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