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1.
Cancer Res ; 84(17): 2761-2775, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-38900938

RESUMO

Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.


Assuntos
Dieta Hiperlipídica , Matriz Extracelular , Obesidade , Microambiente Tumoral , Animais , Obesidade/metabolismo , Obesidade/patologia , Obesidade/complicações , Feminino , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Camundongos , Humanos , Dieta Hiperlipídica/efeitos adversos , Invasividade Neoplásica , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Colágeno Tipo IV/metabolismo
2.
PLoS One ; 13(1): e0190902, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29351349

RESUMO

INTRODUCTION: Generating a nationally representative sample in low and middle income countries typically requires resource-intensive household level sampling with door-to-door data collection. High mobile phone penetration rates in developing countries provide new opportunities for alternative sampling and data collection methods, but there is limited information about response rates and sample biases in coverage and nonresponse using these methods. We utilized data from an interactive voice response, random-digit dial, national mobile phone survey in Ghana to calculate standardized response rates and assess representativeness of the obtained sample. MATERIALS AND METHODS: The survey methodology was piloted in two rounds of data collection. The final survey included 18 demographic, media exposure, and health behavior questions. Call outcomes and response rates were calculated according to the American Association of Public Opinion Research guidelines. Sample characteristics, productivity, and costs per interview were calculated. Representativeness was assessed by comparing data to the Ghana Demographic and Health Survey and the National Population and Housing Census. RESULTS: The survey was fielded during a 27-day period in February-March 2017. There were 9,469 completed interviews and 3,547 partial interviews. Response, cooperation, refusal, and contact rates were 31%, 81%, 7%, and 39% respectively. Twenty-three calls were dialed to produce an eligible contact: nonresponse was substantial due to the automated calling system and dialing of many unassigned or non-working numbers. Younger, urban, better educated, and male respondents were overrepresented in the sample. CONCLUSIONS: The innovative mobile phone data collection methodology yielded a large sample in a relatively short period. Response rates were comparable to other surveys, although substantial coverage bias resulted from fewer women, rural, and older residents completing the mobile phone survey in comparison to household surveys. Random digit dialing of mobile phones offers promise for future data collection in Ghana and may be suitable for other developing countries.


Assuntos
Telefone Celular , Inquéritos Epidemiológicos/métodos , Adolescente , Adulto , Idoso , Viés , Coleta de Dados/métodos , Coleta de Dados/normas , Coleta de Dados/estatística & dados numéricos , Feminino , Gana , Inquéritos Epidemiológicos/normas , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Amostra , Adulto Jovem
3.
South Afr J HIV Med ; 19(1): 721, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214827

RESUMO

BACKGROUND: The emergence of antiretroviral therapy (ART) transformed HIV from a terminal illness to a chronic disease. However, limited access to health services remains one of many barriers to HIV service utilisation by people living with HIV (PLHIV) in low-resource settings. The goal of this study was to describe the barriers to HIV service utilisation in two provinces of Zimbabwe. METHODS: A qualitative descriptive study was conducted with PLHIV and village health workers (VHW) in eight districts within the two provinces. Convenience sampling was used to select the participants. This sampling was limited to communities supported by health facilities with more than 500 PLHIV enrolled into HIV care and treatment. Interviews were audio-recorded and transcripts were subjected to thematic content analysis. RESULTS: A total of 22 community focus group discussions (FGDs) were conducted. Barriers to using HIV services cited in PLHIV and VHW FGDs were similar. These were categorised as health system-related barriers, which include user fees, long waiting times, lack of confidentiality and negative attitudes by healthcare providers, and lack of consistent community-based HIV services. Community-related barriers cited were stigma and discrimination, food insecurity, distance to facilities and counterproductive messaging from religious sectors. Client-related factors reported were inadequate male involvement in HIV-related activities and defaulting after symptoms improved. CONCLUSION: Our assessment has indicated that there are several barriers to the utilisation of HIV services by PLHIV in the two provinces of Zimbabwe. As new strategies and programmes are being introduced in the current resource-constrained era, efforts should be made to understand the needs of the clients. If programmes are designed with an effort to address some of these challenges, there is a possibility that countries will quickly achieve the 90-90-90 targets set by The Joint United Nations Programme on HIV/AIDS.

4.
Phytother Res ; 16(3): 276-80, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12164277

RESUMO

A plant formula and its five components were evaluated independently for their gastric protective effect against ethanol-induced stomach lesions in rats. Aqueous extracts of the plant formula (0.25-2g crude drug/kg orally) and its individual components (at the same dose) all showed significant stomach protective effects dose dependently. However, when these extracts were given to rats at a dose of 0.25 g/kg, the five single-herb preparations did not show any activity, but the formula-extract still exhibited a strong protective effect. These findings suggest the presence of a synergistic effect among the plant components. Chemical examination of the extracts indicated that the major ingredients of the five plants were essential oils, terpenoids, flavonoids, glycosides and saccharides and these may contribute to the stomach protective activity observed.


Assuntos
Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Estômago/efeitos dos fármacos , Alpinia , Animais , Citrus , Curcuma , Cyperus , Etanol/toxicidade , Frutas/química , Lindera , Masculino , Fitoterapia , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Rizoma/química , Estômago/patologia
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