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1.
Mol Ther ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39222637

RESUMO

Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells. In turn, genetic knockout (KO) of FKBP prolyl isomerase 1A (FKBP1A), which encodes a protein targeted by both drugs, was necessary to confer CD19-specific CAR-T cells (19CAR) robust functional resistance to these immunosuppressants. FKBP1AKO 19CAR-T cells maintained potent in vitro functional profiles and controlled in vivo tumor progression similarly to untreated 19CAR-T cells. Moreover, immunosuppressant treatment averted in vivo allorejection permitting FKBP1AKO 19CAR-T cell-driven B cell aplasia. Thus, we demonstrate that genome engineering enables immunosuppressant treatment to improve the therapeutic potential of universal donor-derived CAR-T cells.

2.
Behav Brain Res ; 224(2): 376-86, 2011 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-21723327

RESUMO

The perifornical lateral hypothalamic area (PeFLH), which houses orexin/hypocretin (OX) neurons, is thought to play an important role in arousal, feeding, and locomotor activity. The present study examined behavioural effects of activating PeFLH neurons with microinjections of ionotropic glutamate receptor agonists. Three separate unilateral microinjections of either (1) AMPA (1 and 2mM in 0.1 µL artificial cerebrospinal fluid, ACSF) and ACSF, or (2) NMDA (1 and 10mM in 0.1 µL ACSF), and ACSF were made into the PeFLH of adult male rats. Following each injection, the rats were placed into an open field for behavioural scoring for 45 min. Rats were perfused after the third injection for immunohistochemistry for c-Fos and OX to assess the level of activation of OX neurons. Behavioural analyses showed that, as compared to ACSF conditions, AMPA injections produced a dose-dependent increase in locomotion and rearing that persisted throughout the 45 min recording period, and an increase in drinking. Injection of NMDA at 10mM, but not 1mM, induced a transient increase in locomotion and an increase in feeding. Histological analyses showed that while both agonists increased the number of neurons immunoreactive for c-Fos in the PeFLH, only AMPA increased the number of neurons immunoreactive for both c-Fos and OX. There were positive correlations between the number of c-Fos/OX-immunoreactive neurons and the amounts of locomotion, rearing, and drinking. These results support the role of ionotropic glutamate receptors on OX and other neurons in the PeFLH in the regulation of locomotor and ingestive behaviours.


Assuntos
Comportamento Animal/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Região Hipotalâmica Lateral/fisiologia , N-Metilaspartato/farmacologia , Neurônios/efeitos dos fármacos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , Animais , Relação Dose-Resposta a Droga , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Genes fos/genética , Asseio Animal/efeitos dos fármacos , Movimentos da Cabeça/efeitos dos fármacos , Região Hipotalâmica Lateral/citologia , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , N-Metilaspartato/administração & dosagem , Neuropeptídeos/fisiologia , Orexinas , Ratos , Ratos Wistar , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/administração & dosagem
3.
Genet Med ; 13(7): 651-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21552135

RESUMO

PURPOSE: Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline mutations in the TP53 gene. Although sarcomas, brain tumors, leukemias, breast and adrenal cortical carcinomas are typically recognized as Li-Fraumeni syndrome-associated tumors, the occurrence of gastrointestinal neoplasms has not been fully evaluated. In this analysis, we investigated the frequency and characteristics of gastric cancer in Li-Fraumeni syndrome. METHODS: Pedigrees and medical records of 62 TP53 mutation-positive families were retrospectively reviewed from the Dana-Farber/National Cancer Institute Li-Fraumeni syndrome registry. We identified subjects with gastric cancer documented either by pathology report or death certificate and performed pathology review of the available specimens. RESULTS: Among 62 TP53 mutation-positive families, there were 429 cancer-affected individuals. Gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported two or more cases of gastric cancer, and six (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies. CONCLUSIONS: Early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer.


Assuntos
Síndrome de Li-Fraumeni/genética , Mutação , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Saúde da Família , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Adulto Jovem
4.
Cancer ; 116(2): 497-505, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-19908254

RESUMO

BACKGROUND: Young adult survivors of childhood cancer have an increased risk for treatment-related morbidity and mortality. In this study, the authors assessed how treatment for childhood cancer affects older-adult health and health practices. METHODS: One hundred seven adults treated for childhood cancer between 1947 and 1968, known to have survived past age 50 years, were identified from a single-institution cohort established in 1975. Updated vital status on eligible cases was obtained from public records. Survivors and a control group of their age-matched siblings and cousins completed a mailed survey to assess physical and social function, healthcare practices, and the prevalence of common adult illnesses. RESULTS: Of the 107 survivors known to be alive at age 50 years, 16 were deceased at follow-up; 7 deaths could be associated with prior treatment (second malignancy in radiation field [3], small bowel obstruction after abdominal radiation [2], and cardiac disease after chest irradiation [2]). The 55 survivors (median age, 56 years; range, 51-71 years), and 32 family controls (median age, 58 years; range, 48-70 years), reported similar health practices, health-related quality of life, and social function. However, survivors reported more frequent visits to healthcare providers (P < .05), more physical impairments (P < .05), fatigue (P = .02), hypertension (P = .001), and coronary artery disease (P = .01). An increased risk of hypertension was associated with nephrectomy during childhood (odds ratio, 18.9; 95% confidence interval, 3.0-118.8). CONCLUSIONS: The oldest adult survivors of childhood cancer continue to be at risk for treatment-related complications that potentially decrease their life expectancy and compromise their quality of life.


Assuntos
Nível de Saúde , Neoplasias/terapia , Sobreviventes/estatística & dados numéricos , Adolescente , Idade de Início , Idoso , Atitude Frente a Saúde , Criança , Pré-Escolar , Doença Crônica , Terapia Combinada/efeitos adversos , Comportamentos Relacionados com a Saúde , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Segunda Neoplasia Primária/epidemiologia , Qualidade de Vida
5.
Proteomics ; 9(3): 757-67, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19137550

RESUMO

Green tea polyphenols exhibit multiple antitumor activities, and the mechanisms of action are not completely understood. Previously, we reported that green tea extract (GTE)-induced actin remolding is associated with increased cell adhesion and decreased motility in A549 lung cancer cells. To identify the cellular targets responsible for green tea-induced actin remodeling, we performed 2-DE LC-MS/MS of A549 cells before and after GTE exposure. We have identified 14 protein spots that changed in expression (> or =2-fold) after GTE treatment. These proteins are involved in calcium-binding, cytoskeleton and motility, metabolism, detoxification, or gene regulation. In particular we found upregulation of several genes that modulate actin remodeling and cell migration, including lamin A/C. Our data indicated that GTE-induced lamin A/C upregulation appears to be at the transcriptional level and the increased expression results in the decrease in cell motility, as confirmed by siRNA. The result of the study demonstrates that GTE alters the levels of many proteins involved in growth, motility and apoptosis of A549 cells and their identification may explain the multiple antitumor activities of GTE.


Assuntos
Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Extratos Vegetais/farmacologia , Chá/química , Linhagem Celular Tumoral , Eletroforese em Gel Bidimensional , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Neoplasias Pulmonares/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
J Clin Oncol ; 27(1): 52-60, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19047296

RESUMO

PURPOSE: Partnership for Health (PFH) was found to increase smoking cessation among smokers in the Childhood Cancer Survivors Study (CCSS) at the 8- and 12-month postbaseline follow-up. This report provides outcomes at 2 to 6 years postbaseline; the primary outcome is a four-category smoking status variable (quit at all follow-ups, quit at final follow-up only, smoker at all follow-ups, and smoker at final follow-up only); quit attempts among those who reported smoking at the final follow-up is a secondary outcome. METHODS: PFH was a randomized control trial with two conditions, peer phone counseling (PC) and self-help (SH), that involved smokers (n = 796) enrolled in the CCSS cohort. RESULTS: Long-term quit rates were higher in PC versus SH participants. Long-term smoking cessation outcomes were lower among those who were nicotine dependent, of lower educational levels, and among men, and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy. There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers. CONCLUSION: Cessation rates continue to be significantly higher among participants in the PC condition versus SH, although the differences were not large. This article highlights differences in long-term engagement with smoking cessation among those who received the intervention.


Assuntos
Neoplasias/psicologia , Abandono do Hábito de Fumar , Adulto , Feminino , Seguimentos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Sobreviventes
7.
JAMA ; 299(11): 1315-9, 2008 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-18349092

RESUMO

CONTEXT: Individuals with Li-Fraumeni syndrome (LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds. OBJECTIVE: To gather preliminary data with which to evaluate F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds. DESIGN, SETTING, AND PARTICIPANTS: Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill-health were offered FDG-PET/CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist. MAIN OUTCOME MEASURE: The primary outcome was the detection of new primary cancers using FDG-PET/CT scanning. RESULTS: Of 15 individuals, baseline FDG-PET/CT scan identified asymptomatic cancers in 3 (20%). Two individuals had papillary thyroid cancers (stage II and stage III) and one individual had stage II esophageal adenocarcinoma. CONCLUSIONS: These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration.


Assuntos
Síndrome de Li-Fraumeni/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada Espiral , Imagem Corporal Total , Adulto , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18 , Genes p53 , Heterozigoto , Humanos , Síndrome de Li-Fraumeni/genética , Masculino , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Projetos Piloto , Compostos Radiofarmacêuticos
8.
JAMA ; 298(24): 2869-76, 2007 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-18159056

RESUMO

CONTEXT: Information on the prevalence of pathogenic BRCA1 mutation carriers in racial/ethnic minority populations is limited. OBJECTIVE: To estimate BRCA1 carrier prevalence in Hispanic, African American, and Asian American female breast cancer patients compared with non-Hispanic white patients with and without Ashkenazi Jewish ancestry. DESIGN, SETTING, AND PARTICIPANTS: We estimated race/ethnicity-specific prevalence of BRCA1 in a population-based, multiethnic series of female breast cancer patients younger than 65 years at diagnosis who were enrolled at the Northern California site of the Breast Cancer Family Registry during the period 1996-2005. Race/ethnicity and religious ancestry were based on self-report. Weighted estimates of prevalence and 95% confidence intervals (CIs) were based on Horvitz-Thompson estimating equations. MAIN OUTCOME MEASURE: Estimates of BRCA1 prevalence. RESULTS: Estimates of BRCA1 prevalence were 3.5% (95% CI, 2.1%-5.8%) in Hispanic patients (n = 393), 1.3% (95% CI, 0.6%-2.6%) in African American patients (n = 341), and 0.5% (95% CI, 0.1%-2.0%) in Asian American patients (n = 444), compared with 8.3% (95% CI, 3.1%-20.1%) in Ashkenazi Jewish patients (n = 41) and 2.2% (95% CI, 0.7%-6.9%) in other non-Hispanic white patients (n = 508). Prevalence was particularly high in young (<35 years) African American patients (5/30 patients [16.7%]; 95% CI, 7.1%-34.3%). 185delAG was the most common mutation in Hispanics, found in 5 of 21 carriers (24%). CONCLUSIONS: Among African American, Asian American, and Hispanic patients in the Northern California Breast Cancer Family Registry, the prevalence of BRCA1 mutation carriers was highest in Hispanics and lowest in Asian Americans. The higher carrier prevalence in Hispanics may reflect the presence of unrecognized Jewish ancestry in this population.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Genes BRCA1 , Adulto , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/genética , Asiático/estatística & dados numéricos , California/epidemiologia , Análise Mutacional de DNA , Feminino , Triagem de Portadores Genéticos , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Humanos , Judeus/genética , Judeus/estatística & dados numéricos , Pessoa de Meia-Idade , Mutação , Prevalência , Sistema de Registros
9.
Lab Invest ; 87(5): 456-65, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17351649

RESUMO

Green tea polyphenols exhibit multiple antitumor activities in various in vitro and in vivo tumor models, and the mechanisms of action are not clear. Previously, we found that green tea extract (GTE) regulates actin remodeling in different cell culture systems. Actin remodeling plays an important role in cancer cell morphology, cell adhesion, motility, and invasion. Using proteomic approaches, we found GTE-induced expression of annexin-I, a multifunctional actin binding protein, in these cell lines. In this study, we aimed to further define the functional role of GTE-induced annexin-I expression in actin remodeling, cell adhesion, and motility in lung adenocarcinoma A549 cells. We found that GTE stimulates the expression of annexin-I in a dose-dependent fashion. The GTE-induced annexin-I expression appears to be at the transcription level, and the increased annexin-I expression mediates actin polymerization, resulting in enhanced cell adhesion and decreased motility. Annexin-I specific interference resulted in loss of GTE-induced actin polymerization and cell adhesion, but not motility. In fact, annexin-I specific interference itself inhibited motility even without GTE. Together, annexin-I plays an important role in GTE-induced actin remodeling, and it may serve as a potential molecular target associated with the anticancer activities of green tea.


Assuntos
Actinas/metabolismo , Adenocarcinoma/metabolismo , Anexina A1/metabolismo , Anticarcinógenos/farmacologia , Camellia sinensis/química , Neoplasias Pulmonares/metabolismo , Extratos Vegetais/farmacologia , Actinas/genética , Adenocarcinoma/tratamento farmacológico , Anexina A1/genética , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Polímeros , Proteômica , RNA Mensageiro/metabolismo
10.
Cancer Causes Control ; 18(4): 423-30, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17297556

RESUMO

OBJECTIVE: To characterize the smoking-related services available to childhood cancer survivors and describe organizational characteristics that were related to institutions' capacity to provide smoking services. METHODS: Institutions affiliated with the Children's Oncology Group were surveyed from 2003 to 2004. RESULTS: Of the 132 responding institutions, 85% assessed the smoking status of their cancer survivors intermittingly, but only 3% assessed smoking status at every visit, as recommended by the PHS guidelines. A minority of sites offered either smoking prevention (39%) or cessation (25%) services; 58% of sites had a mechanism in place to refer survivors for cessation services. In multivariate analyses, the most parsimonious model predicting capacity for smoking service delivery included barriers, respondents' attitudes, complexity, and institutional stability. CONCLUSIONS: These data highlight an important need to improve the availability of smoking services for childhood cancer survivors. Additionally, these findings will inform the development of future interventions that are sensitive to barriers and facilitators to providing prevention services.


Assuntos
Neoplasias/prevenção & controle , Serviços Preventivos de Saúde/normas , Medicina Preventiva/normas , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Sobreviventes , Adolescente , Atitude do Pessoal de Saúde , Institutos de Câncer , Criança , Continuidade da Assistência ao Paciente/organização & administração , Feminino , Prática de Grupo , Acessibilidade aos Serviços de Saúde , Hospitais Gerais , Hospitais Pediátricos , Humanos , Masculino , Massachusetts , Fumar/efeitos adversos , Estados Unidos
11.
Int J Cancer ; 120(1): 111-20, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17019707

RESUMO

Using a multistep human urothelial model, we previously showed that green tea extract (GTE) selectively modulates actin remodeling in transformed cells (MC-T11), which resulted in increased cell adhesion and reduced cell motility (Lu et al., Clin Cancer Res 2005;11:1675-83). This study further analyzed which actin binding proteins (ABPs) might be involved in this process. Proteomic profiles of GTE treated and untreated MC-T11 cells using two-dimensional gel electrophoresis coupled with liquid chromatography tandem mass spectrometry (LC/MS/MS) and matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) identified 20 GTE-induced proteins. Among them, 3 were ABPs (tropomodulin, cofilin and annexin-I), and only annexin-I showed a dose- and time-dependent expression. The increased annexin-I correlated with actin remodeling, and was the result of transcription level up-regulation, as determined by RT-PCR, pull-down immunoblot and siRNA analyses. 5-Azacytidine, a DNA methylation inhibitor, exhibited no effect on annexin-I expression when used alone, but had an additive effect for GTE-induced annexin-I expression. Immunohistochemistry of bladder cancer tissue array showed a decrease of annexin-I expression in carcinoma in situ and low grade papillary carcinoma (n = 32, 0% positive) compared to nontumor urothelium (n = 18, 89% positive) (p < 0.001 by Fisher exact test), but increased in some (6 of 15, 40%) high-grade tumors. Together, GTE induced annexin-I expression plays a role in regulating actin remodeling and decreased annexin-I expression is a common event in early stage of bladder cancer development.


Assuntos
Actinas/metabolismo , Anexina A1/metabolismo , Extratos Vegetais/farmacologia , Chá , Anexina A1/antagonistas & inibidores , Anexina A1/genética , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Estudos de Casos e Controles , Linhagem Celular Transformada , Eletroforese em Gel Bidimensional , Imunofluorescência , Humanos , Immunoblotting , Técnicas Imunoenzimáticas , Imunoprecipitação , Mapeamento de Peptídeos , Proteoma , RNA Interferente Pequeno/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Urotélio/metabolismo , Urotélio/patologia
12.
J Agric Food Chem ; 54(26): 9792-7, 2006 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-17177503

RESUMO

This study was designed to investigate the cancer preventive activities of wheat bran (WB) oil. We studied the colon cancer preventive effects of WB oil and its subfractions in the Apc(min/+) mouse model, a recognized mouse model for human colorectal cancer, and used human colon cancer cell lines (HCT-116 and HT-29) to identify possible active fractions in WB oil. Our results showed that the oil fraction of WB was more active than the water fraction against the growth of human colon cancer cell lines and that 2% WB oil significantly inhibited the overall tumorigenesis by 35.7% (p < 0.0001) in the Apc(min/+) mouse model. The WB oil was further fractioned into nonpolar lipids and phytochemicals and the phytochemical fraction was fractionated into phytosterols and phytosterol ferulates, 5-alk(en)ylresorcinols, and unidentified constituents by normal phase silica gel column chromatography. Results on cell culture showed that the phytochemical fraction had a higher inhibitory effect on HCT-116 human colon cancer cells than that of WB oil, whereas the nonpolar lipid fraction had less growth inhibitory effectiveness. However, neither fractions showed a stronger inhibition than WB oil in the Apc(min/+) mouse model. The current results demonstrate, for the first time, the intestinal cancer preventive activity of WB oil. The active ingredients, however, remain to be identified.


Assuntos
Neoplasias do Colo/patologia , Fibras na Dieta , Neoplasias Intestinais/prevenção & controle , Óleos de Plantas/administração & dosagem , Animais , Divisão Celular/efeitos dos fármacos , Fibras na Dieta/análise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Transplante de Neoplasias , Óleos de Plantas/química
13.
Cancer ; 107(8 Suppl): 2006-14, 2006 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-16977597

RESUMO

The Asian American Network for Cancer Awareness, Research, and Training (AANCART) is the first special populations network for Asian Americans on a national basis and includes collaborating organizations from Boston, New York, Houston, Seattle, San Francisco, Los Angeles, Hawaii, and Sacramento (where it is headquartered at the University of California, Davis). NCI funding of AANCART in 2000 brought together investigators and leaders from 9 cities across 6 states to establish an infrastructure for addressing cancer awareness, research, and training. Since 2000, AANCART has conducted needs assessments, held community awareness activities and trainings, trained trainees, sponsored National Asian American Cancer Control Academies, and produced presentations, publications, and grants. All specific aims have been attained, including the establishment of an infrastructure to promote Asian American cancer awareness, research, and training in 4 targeted regions; the establishment of partnerships to promote accrual to clinical trials, training, and pilot studies; and the formulation and successful implementation of grant-funded research to reduce the cancer burden among Asian Americans. AANCART's first 5 years have increased cancer awareness, trained special populations scientists, and advanced the field of Asian American cancer control research. Cancer 2006. (c) 2006 American Cancer Society.


Assuntos
Asiático , Redes Comunitárias/organização & administração , Educação em Saúde , Neoplasias/etnologia , Apoio à Pesquisa como Assunto , Humanos , Estados Unidos
14.
Cancer ; 107(4): 806-14, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16832795

RESUMO

BACKGROUND: Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction. METHODS: We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently-diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: (1) an initial motivational and goal-setting telephone intervention session delivered by the health educator; (2) three sets of computer-generated materials specifically tailored to individual responses from the baseline survey; (3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and (4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened. RESULTS: 494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06-2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two-thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups. CONCLUSIONS: This study is the one of the first, to our knowledge, to address skin cancer risk-reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Melanoma/diagnóstico , Melanoma/prevenção & controle , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/prevenção & controle , Adolescente , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Melanoma/psicologia , Pessoa de Meia-Idade , Fatores de Risco , Autoexame , Irmãos , Neoplasias Cutâneas/psicologia
15.
Prev Med ; 42(6): 435-42, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16626797

RESUMO

OBJECTIVE: We report on the process evaluation of an efficacious national smoking cessation intervention for adult survivors of childhood cancer. We examine associations between intervention implementation characteristics and study outcomes, as well as participant characteristics related to level of involvement in the intervention. METHODS: The study was conducted at the Dana-Farber Cancer Institute in Boston, Massachusetts, from 1999-2001. Participants (n = 398) were randomly assigned to receive a proactive telephone-based peer counseling intervention. They received up to 6 counseling calls, individually tailored and survivor-targeted materials, and nicotine replacement therapy (NRT) patches if they were prepared to quit smoking. RESULTS: Forty-two percent of survivors participated in the maximum number of calls (5-6), and 29% of participants requested and received NRT. Total counseling time was an average of 51 min. Quit status at follow-up was related to intervention dose, and participants who received NRT were significantly more likely to make a 24-h quit attempt. Demographic variables (females, White), higher daily smoking rate, poorer perceived health and moderate perceived risk of smoking were significantly related to greater intervention involvement. CONCLUSIONS: A brief peer-delivered, telephone counseling intervention is an effective way to intervene with adult survivors of childhood cancer who are smoking. Findings from the process evaluation data (call length and number, frequency, and spacing) will inform future telephone counseling cessation programs.


Assuntos
Aconselhamento , Neoplasias/psicologia , Abandono do Hábito de Fumar/métodos , Sobreviventes/psicologia , Telefone , Adulto , Demografia , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Avaliação de Processos e Resultados em Cuidados de Saúde , Grupo Associado , Avaliação de Programas e Projetos de Saúde , Prevenção do Hábito de Fumar
16.
Cancer Epidemiol Biomarkers Prev ; 15(2): 359-63, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16492929

RESUMO

BACKGROUND: First-degree relatives of patients with breast or ovarian cancer have increased risks for these cancers. Little is known about how their risks vary with the patient's cancer site, carrier status for predisposing genetic mutations, or age at cancer diagnosis. METHODS: We evaluated breast and ovarian cancer incidence in 2,935 female first-degree relatives of non-Hispanic White female patients with incident invasive cancers of the breast (n = 669) or ovary (n = 339) who were recruited from a population-based cancer registry in northern California. Breast cancer patients were tested for BRCA1 and BRCA2 mutations. Ovarian cancer patients were tested for BRCA1 mutations. We estimated standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) for breast and ovarian cancer among the relatives according to the patient's mutation status, cancer site, and age at cancer diagnosis. RESULTS: In families of patients who were negative or untested for BRCA1 or BRCA2 mutations, risks were elevated only for the patient's cancer site. The breast cancer SIR was 1.5 (95% CI, 1.2-1.8) for relatives of breast cancer patients, compared with 1.1 (95% CI, 0.8-1.6) for relatives of ovarian cancer patients (P = 0.12 for difference by patient's cancer site). The ovarian cancer SIR was 0.9 (95% CI, 0.5-1.4) for relatives of breast cancer patients, compared with 1.9 (95% CI, 1.0-4.0) for relatives of ovarian cancer patients (P = 0.04 for difference by site). In families of BRCA1-positive patients, relatives' risks also correlated with the patient's cancer site. The breast cancer SIR was 10.6 (95% CI, 5.2-21.6) for relatives of breast cancer patients, compared with 3.3 (95% CI, 1.4-7.3) for relatives of ovarian cancer patients (two-sided P = 0.02 for difference by site). The ovarian cancer SIR was 7.9 (95% CI, 1.2-53.0) for relatives of breast cancer patients, compared with 11.3 (3.6-35.9) for relatives of ovarian cancer patients (two-sided P = 0.37 for difference by site). Relatives' risks were independent of patients' ages at diagnosis, with one exception: In families ascertained through a breast cancer patient without BRCA mutations, breast cancer risks were higher if the patient had been diagnosed before age 40 years. CONCLUSION: In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patient's cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Neoplasias Ovarianas/genética , Adulto , Idade de Início , Idoso , Neoplasias da Mama/epidemiologia , Éxons , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Risco
17.
Gastroenterology ; 130(1): 73-9, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16401470

RESUMO

BACKGROUND & AIMS: Hereditary colorectal cancer is associated most commonly with the hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndromes. We investigated the prevalence of early onset colorectal cancer and the frequency of p53 germline mutations in 64 families from a Li-Fraumeni syndrome (LFS) registry. METHODS: Patients with documented colorectal cancer and a diagnosis at or before age 50 were included. P53 analyses were performed through germline mutational analyses using standard molecular techniques. RESULTS: Among the 397 patients and 64 families in the classic LFS registry, a total of 11 patients (2.8%) from 10 different families (15.6%) met criteria for classic LFS and had documented colorectal cancer at less than 50 years of age. The mean age at diagnosis in this group was 33 years and of these patients 4 developed colorectal cancer before age 21 (ages, 9, 11, 15, and 20 y). All families that were tested for p53 mutations (8 of 10) had evidence of germline mutations by sequence analysis; therefore, 12.5% of the total number of families in the registry had colorectal cancer at age less than 50 years and a documented germline p53 mutation. Mutations primarily were missense or nonsense and were located between exons 4-10. CONCLUSIONS: LFS patients with germline p53 mutations may have an increased susceptibility to colorectal cancer and present up to several decades earlier than the general population. LFS should be considered when a young patient presents with colorectal cancer.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Genes p53 , Síndrome de Li-Fraumeni/complicações , Adulto , Idade de Início , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Síndrome de Li-Fraumeni/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros/estatística & dados numéricos , Fatores de Risco
18.
J Clin Oncol ; 23(36): 9187-97, 2005 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-16361621

RESUMO

PURPOSE: To examine the prevalence and predictors of health insurance coverage and the difficulties obtaining coverage in a large cohort of childhood cancer survivors. PATIENTS AND METHODS: This study included 12,358 5-year survivors of childhood cancer and 3,553 sibling controls participating in the Childhood Cancer Survivor Study. Data were collected by surveys distributed in 1994 (baseline) and 2000 (follow-up). RESULTS: At baseline, 83.9% of adult survivors, compared with 88.3% of siblings, had health insurance coverage (P < .01); 6 years later, small but significant survivor-sibling differences remained (88% v 91%; P < .01). Twenty-nine percent of survivors reported having had difficulties obtaining coverage, compared with only 3% of siblings (P < .01). In multivariate analysis of survivors 18 years of age or older, factors associated with being uninsured included younger age at diagnosis (diagnosis age of 0 to 4 years; odds ratio [OR] = 1.7; 95% CI, 1.3 to 2.2), male sex (OR = 1.3; 95% CI, 1.2 to 1.5), age at baseline survey (age 22 to 24 years; OR = 1.6; 95% CI, 1.2 to 2.1), lower level of attained education (less than high school, OR = 2.6, 95% CI, 2.1 to 3.3; high school graduate, OR = 2.1, 95% CI, 1.8 to 2.5), income less than 20,000 dollars (OR = 5.6, 95% CI, 4.5 to 7.1), marital status (widowed/divorced/separated; OR = 1.3; 95% CI, 1.1 to 1.6), smoking status (current smoker, OR = 2.0, 95% CI, 1.7 to 2.3; former smoker, OR = 1.4, 95% CI, 1.2 to 1.8), and treatment that included cranial radiation (OR = 1.3, 95% CI, 1.0 to 1.6). CONCLUSION: Compared with siblings, adult survivors of childhood cancer had significantly lower rates of health insurance coverage and more difficulties obtaining coverage. Since lack of coverage likely has serious health and financial implications for this at-risk population, any disparity in availability and quality of coverage is of great concern.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/economia , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Definição da Elegibilidade , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Neoplasias/terapia , Razão de Chances , Prognóstico , Fatores de Risco , Fumar , Sobreviventes
19.
J Clin Oncol ; 23(27): 6516-23, 2005 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-16116148

RESUMO

PURPOSE: Cancer survivors smoke at rates that are only slightly lower than the general population. This article reports on the final outcomes of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study (CCSS). METHODS: This study is a randomized control trial with follow-up at 8 and 12 months that involved smokers (n = 796) enrolled onto the CCSS cohort. Participants were randomly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor, tailored and targeted materials, and free nicotine replacement therapy. The intervention was delivered by telephone and postal service mail. RESULTS: The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month (16.8% v 8.5%; P < .01) and 12-month follow-ups (15% v 9%; P < or = .01). Controlling for baseline self-efficacy and readiness to change, the intervention group was twice as likely to quit smoking, compared with the self-help group. Smoking cessation rate increased with an increase in the number of counseling calls. The cost of delivering the intervention was approximately 300 dollars per participant. The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit. CONCLUSION: Interventions to prevent future illnesses are of critical importance to childhood cancer survivors. The Partnership for Health intervention resulted in a doubling of smoking cessation quit rates. Because of the seriousness of smoking among childhood cancer survivors, this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke.


Assuntos
Aconselhamento , Nicotina/antagonistas & inibidores , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/terapia , Educação de Pacientes como Assunto/métodos , Valor Preditivo dos Testes , Prevalência , Probabilidade , Valores de Referência , Fatores de Risco , Grupos de Autoajuda , Distribuição por Sexo , Abandono do Hábito de Fumar/métodos , Sobreviventes , Estados Unidos
20.
Carcinogenesis ; 26(11): 1934-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15958519

RESUMO

Huanglian (Coptidis rhizoma), a widely used herb in traditional Chinese medicine, has been shown recently to possess anticancer activities. However, the molecular mechanism underlying the anticancer effect of the herb is poorly understood. Specifically, whether huanglian extract affects the expression of cancer-related genes has not been defined. This study used DNA microarray technology to examine the effect of the herbal extract on expression of the common genes involved in carcinogenesis in two human breast cancer cell lines, the ER-positive MCF-7 and ER-negative MDA-MB-231 cells. Treatment of the cancer cells with huanglian extract markedly inhibited their proliferation in a dose- and time-dependent manner. The growth inhibitory effect was much more profound in MCF-7 cell line than that in MDA-MB-231 cells. DNA microarray assay revealed that treatment with huanglian dramatically increased the mRNA expression of interferon-beta (IFN-beta) and tumor necrosis factor-alpha in MCF-7 cells. Quantitative analysis by real-time PCR or western blotting confirmed the upregulation of the two genes (especially IFN-beta) in MCF-7 cells, but not in MDA-MB-231 cells. Addition of neutralizing antibody against IFN-beta to culture medium markedly inhibited the huanglian-induced antiproliferative effect, confirming the involvement of IFN-beta in the huanglian's effect and also suggesting an autocrine pathway for the action of IFN-beta in this setting. Given that IFN-beta is among the most important anticancer cytokines, the upregulation of this gene by huanglian is, at least in part, responsible for its antiproliferative effect. The results of this study implicate huanglian as a promising herb for chemoprevention and chemotherapy of certain cancers.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Interferon Tipo I/metabolismo , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Medicina Herbária , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Estrogênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Regulação para Cima
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