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1.
BMC Cancer ; 24(1): 493, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637770

RESUMO

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).


Assuntos
Neoplasias da Próstata , Treinamento Resistido , Masculino , Humanos , Idoso , Creatina/uso terapêutico , Creatina/farmacologia , Qualidade de Vida , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/patologia , Androgênios , Força Muscular , Composição Corporal , Processos Neoplásicos , Método Duplo-Cego , Suplementos Nutricionais/efeitos adversos , Músculos/patologia , Poliésteres/farmacologia , Poliésteres/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Photodiagnosis Photodyn Ther ; 45: 103951, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38161036

RESUMO

Metal-free near-infrared absorbing photosensitizers (PS) have been considered promising candidates for photodynamic therapy. Curcumin, curcuminoid, and its derivatives have therapeutic values due to their anti-inflammatory, antifungal, and antiproliferative properties. Curcuminoid-BF2 chelates have also been studied as cell imaging probes, however, their applications in photodynamic therapy are rare. In this article, we describe the synthesis and therapeutic evaluation of quinolizidine fused curcuminoid-BF2 chelate (Quinolizidine CUR-BF2) containing an acid-sensitive group. This donor-acceptor-donor curcuminoid-BF2 derivative exhibits absorption and emission in the deep red region with an absorption band maximum of ∼647 nm and a weak emission band at approximately 713 nm. It is interesting to note that this derivative has a high molar extinction coefficient (164,655 M-1cm-1). Quinolizidine CUR-BF2 possesses intramolecular charge transfer properties, facilitating the production of singlet oxygen (1O2), which plays a crucial role in cell death. Additionally, Quinolizidine CUR-BF2 can enable the selective release of active ingredients in an acidic medium (pH 5). Furthermore, the nanoaggregates of PS were prepared by encapsulating Quinolizidine CUR-BF2 within Pluronic F127 block co-polymer for better water-dispersibility and enhanced cellular uptake. Dark cytotoxicity of nanoaggregates was found to be negligible, whereas they exhibited significant photoinduced cytotoxicity towards cancer cells (MCF-7 and A549) under irradiation of 635 nm light. Further, the cell death pathway using Quinolizidine CUR-BF2 nanoaggregates as PS is found to occur through apoptosis. Specifically, the present study deals with the successful preparation of Quinolizidine CUR-BF2 nanoaggregates for enhanced water-dispersibility and cellular uptake as well as the efficacy evaluation of developed nanoaggregates for photodynamic therapy.


Assuntos
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Diarileptanoides , Células A549 , Células MCF-7 , Fármacos Fotossensibilizantes/farmacologia , Água
3.
Cancers (Basel) ; 15(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37958345

RESUMO

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas. The straight line distances of the patients' residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from "The Michigan Population Studies Center", based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients.

4.
Cancer ; 127(13): 2204-2212, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33765337

RESUMO

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. RESULTS: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. CONCLUSIONS: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Conduta Expectante
5.
J Family Med Prim Care ; 9(8): 4174-4180, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33110828

RESUMO

CONTEXT: One of the major obstacles in treating TB is the patient's nonadherence to the treatment regimen resulting in prolonged disease transmission and development of resistance to anti-TB drugs. An individual's mental health affects his/her adaptation to the disease. Mental health issues and TB both are inextricably connected and research into this area will provide an opportunity to develop a more holistic model of TB treatment and prevention. AIMS: The aim of this study is to investigate the prevalence of mental health issues in patients with TB and its influence on individual perception of well-being with an emphasis on psychopathology as a major obstacle to treatment adherence. Research into this area will provide an opportunity to develop a more holistic model of TB treatment and prevention. SETTINGS AND DESIGN: Primary data were collected with the help of ASHA workers, and primary survey-based study was designed. METHODS AND MATERIAL: A total of 249 diagnosed Tuberculosis cases were included in the study. A digitalized version of the PGIHQN-1 questionnaire was made and used to separate the psychiatric population from the normal group. Asha workers were trained to use the digital version on tablets. STATISTICAL ANALYSIS USED: Using Microsoft Excel, Graphic Tables, and corelation were done using SPSS Statistics. RESULTS: Mental health issues were found in diagnosed TB cases, which required further evaluations. Along with mental health issues, limited resources, gender, limited education, lack of proper knowledge about the disease, having responsibilities (Marital status), locality were found to be the important factors that complicate TB outcomes, hence should be taken into consideration while imparting psychological interventions. CONCLUSION: Mental health issues complicate TB outcome and hence need to be properly addressed, and thorough psychoeducation, psychological first aid (listen, protect, connect, model& teach), and timely intervention in the form of proper diagnosis and specific treatment and rehabilitation are needed.

6.
Clin Genitourin Cancer ; 18(4): 274-283.e5, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32335059

RESUMO

PURPOSE: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT). PATIENTS AND METHODS: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey. RESULTS: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains. CONCLUSION: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Braquiterapia/mortalidade , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/secundário , Qualidade de Vida , Idoso , Terapia Combinada , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Conduta Expectante
7.
Am Soc Clin Oncol Educ Book ; 37: 319-329, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28561652

RESUMO

The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel-Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies. The U.S. Food and Drug Administration (FDA) has thus approved a total of nine targeted therapies since 2005, including VEGF tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, sorafenib, and lenvatinib), a monoclonal antibody targeting VEGF (bevacizumab), mTOR inhibitors (temsirolimus and everolimus), and a multityrosine kinase inhibitor (cabozantinib). Furthermore, the development of immune checkpoint inhibitors has again shifted the mRCC therapeutic landscape with the FDA's approval of nivolumab. Herein, we discuss the unprecedented changes in the field of clear cell histology mRCC in both the first-line and salvage settings, and we also discuss future therapies and recommend a treatment paradigm on sequencing of these agents.


Assuntos
Carcinoma de Células Renais/terapia , Neovascularização Patológica/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/uso terapêutico , Metástase Neoplásica , Proteínas de Neoplasias/genética , Neovascularização Patológica/epidemiologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Pirróis/uso terapêutico , Quinolinas/uso terapêutico , Sorafenibe , Sunitinibe , Proteína Supressora de Tumor Von Hippel-Lindau/genética
8.
Clin Genitourin Cancer ; 15(4): e573-e582, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28139444

RESUMO

BACKGROUND: The real-world survival outcomes and prognostic factors among patients receiving first-line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. PATIENTS AND METHODS: Adult patients diagnosed with RCC and treated with first-line targeted therapy were identified from the Surveillance, Epidemiology, and End Results-Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006-2009) or late (2010-2012) targeted therapy era cohorts by the year of the first-line targeted therapy initiation. Overall survival (OS) was measured from first-line targeted therapy initiation and compared between the 2 cohorts using Kaplan-Meier analyses. The prognostic factors for OS were assessed using a multivariable-adjusted Cox model. RESULTS: A total of 604 and 641 aRCC patients (mean age, 68 years; ∼60% male in both cohorts) initiated first-line targeted therapy during the early and late targeted therapy eras, respectively. OS was significantly longer in the late than in the early targeted therapy era. Higher tumor grades (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.31-2.00) and lung (HR, 1.27; 95% CI, 1.06-1.53), bone (HR, 1.37; 95% CI, 1.13-1.66), and liver (HR, 1.42; 95% CI, 1.10-1.84) metastases were associated with significantly shorter OS. Previous nephrectomy (HR, 0.55; 95% CI, 0.42-0.72) and pazopanib as first-line targeted therapy relative to sorafenib (HR, 0.56; 95% CI, 0.37-0.85) or sunitinib (HR, 0.65; 95% CI, 0.44-0.95) were associated with significantly longer OS. CONCLUSION: The results of these real-world analyses suggest progress in aRCC management and identified positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bone, or liver metastasis) prognostic factors among patients receiving first-line targeted therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Nefrectomia/métodos , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indazóis , Indóis/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Prognóstico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Programa de SEER , Sorafenibe , Sulfonamidas/uso terapêutico , Sunitinibe , Análise de Sobrevida , Resultado do Tratamento
9.
Crit Rev Oncog ; 22(1-2): 13-21, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29604933

RESUMO

The transcription factor Yin Yang 1 (YY1) is a ubiquitously expressed protein involved in several biological functions, including embryogenesis, differentiation, replication, and cellular proliferation. YY1 can both activate and repress transcription depending on its interactions with other transcription factors and co-factors. It affects the transcription of a large number of mammalian and viral genes. In this review, we focus on the role of YY1 in cancer biology, including its expression, function, regulation by other upstream factors, and some of its more significant downstream effectors. We also discuss its context-dependent and tumor-specific role in human cancer progression, roles as a prognostic marker, and how its interactions with other cancer-associated factors can be exploited to develop novel targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Neoplasias/genética , Fator de Transcrição YY1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , Neoplasias/terapia , Prognóstico
11.
Cancer Res ; 76(17): 5175-85, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27312530

RESUMO

In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175-85. ©2016 AACR.


Assuntos
Antígeno CD24/metabolismo , Carcinoma de Células de Transição/patologia , Receptores Androgênicos/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/patologia , Fator de Transcrição YY1/metabolismo , Animais , Western Blotting , Carcinoma de Células de Transição/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Proteínas Correpressoras , Proteínas de Ligação a DNA , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imunoprecipitação , Masculino , Camundongos , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Neoplasias da Bexiga Urinária/metabolismo
12.
J Cancer Surviv ; 9(1): 115-25, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25164513

RESUMO

PURPOSE: Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases. METHODS: Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention. RESULTS: Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p's > 0.05). CONCLUSIONS: This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings. IMPLICATIONS FOR CANCER SURVIVORS: Senior survivors' have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.


Assuntos
Neoplasias/mortalidade , Tai Chi Chuan/métodos , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Citocinas , Feminino , Humanos , Hidrocortisona , Inflamação , Pessoa de Meia-Idade , Sobreviventes , Resultado do Tratamento
13.
Prostate ; 75(4): 390-8, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25408531

RESUMO

BACKGROUND: Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. METHODS: A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset. RESULTS: In the 635,443 males analyzed, 18,105 had PC. First-degree RRs ranged from 2.46 (=1 first-degree relative affected, CI = 2.39-2.53) to 7.65 (=4 first-degree relatives affected, CI = 6.28-9.23). Second-degree RRs for probands with 0 affected first-degree relatives ranged from 1.51 (≥1 second-degree relative affected, CI = 1.47-1.56) to 3.09 (≥5 second-degree relatives affected, CI = 2.32-4.03). Third-degree RRs with 0 affected first- and 0 affected second-degree relatives ranged from 1.15 (≥1 affected third-degree relative, CI = 1.12-1.19) to 1.50 (≥5 affected third-degree relatives, CI = 1.35-1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first-degree relative diagnosed before age 50 years (CI = 1.12-1.19) and RR = 1.78 for >1 second-degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different. CONCLUSIONS: A more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated from summary family history. The presence of PC in second- and even third-degree relatives contributes significantly to risk. Maternal family history is just as significant as paternal family history. PC RRs based on a proband's complete constellation of affected relatives will allow patients and care providers to make more informed screening, monitoring, and treatment decisions.


Assuntos
Predisposição Genética para Doença , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Família , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Sistema de Registros , Estudos Retrospectivos , Medição de Risco
14.
J Immunother ; 37(7): 360-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25075565

RESUMO

Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Interleucina-2/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Interleucina-2/efeitos adversos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
Target Oncol ; 9(1): 63-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23609056

RESUMO

We compared acute toxicity, drug exposure, in-hospital mortality, and inpatient length of stay between two currently recommended dosing protocols (from the National Comprehensive Cancer Network Guidelines) of high-dose interleukin-2 (IL-2) treatment for patients with metastatic melanoma. Patients with metastatic melanoma who received high-dose IL-2 treatment between 2003 and 2010 were identified. Chemotherapy orders, electronic medical records, paper medical charts, and patient discharge summaries were reviewed retrospectively. We identified 13 patients who had received 600,000 units/kilogram (kg)/dose and 15 patients who had received 720,000 units/kg/dose. Patients in the 720,000 units/kg/dose group had a higher rate of grade 3 and 4 bilirubin elevations (34 vs. 12 %), weight gain (any grade, 96 vs. 89 %), and thrombocytopenia (any grade, 75 vs. 65 %). Patients receiving the higher dose also experienced more dose-limiting neurotoxicity (45 vs. 23 %), large-volume diarrhea (15 vs. 0 %), and hepatotoxicity (7 vs. 0 %). There was no in-hospital mortality during treatment in either group. The average length of stay was similar between both groups (5 days, SD = 1 for both groups), and the median cumulative IL-2 exposure was similar between both groups for the first course (10.1 vs.10.5 million units/kg) and for all courses (approximately 11-12 million units/kg). Both high-dose IL-2 protocols had comparable in-hospital mortality and cumulative IL-2 exposure. The 720,000 units/kg/dose dosing scheme did not shorten the length of stay but did lead to greater acute toxicity. Therefore, as a result, we recommend 600,000 units/kg/dose when deciding between the two regimens.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Relação Dose-Resposta a Droga , Feminino , Mortalidade Hospitalar , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Adulto Jovem
16.
J Cancer Surviv ; 8(1): 60-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24170679

RESUMO

PURPOSE: Fatigue is a commonly reported symptom by prostate cancer survivors and is associated with significant distress and declines in quality of life. Qigong is a mind-body activity that consists of both physical activity and meditative aspects. This 12-week randomized controlled trial examined the feasibility and efficacy of a Qigong intervention for improving older prostate cancer survivors' levels of fatigue and distress. METHODS: Forty older (median age = 72, range = 58-93), fatigued (cut-off value of ≥ 1 on the CTCAEv4.0, >20 on a fatigue grading scale), and sedentary (<150 min of moderate exercise/week) prostate cancer survivors were randomized to 12 weeks of Qigong or stretching classes. Primary outcomes were feasibility (i.e., retention and class attendance rates) and fatigue [Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)], and secondary outcome was distress [Brief Symptom Inventory-18 (BSI-18)]. RESULTS: Study retention rates did not significantly differ between study groups (Qigong = 80 %, stretching = 65 %, p = 0.48). The Qigong group had significantly higher class attendance than the stretching group (p = 0.04). The Qigong group had significantly greater improvements in the FACIT-Fatigue (p = 0.02) and distress (i.e., BSI-18 Somatization, Anxiety, & Global Severity Index, p's < 0.05), than the Stretching group. CONCLUSIONS: This 12-week Qigong intervention was feasible and potentially efficacious in improving senior prostate cancer survivors' levels of fatigue and distress levels. Future, larger definitive randomized controlled trials are needed to confirm these benefits in older prostate cancer survivors and in racially and ethnically diverse populations. IMPLICATIONS FOR CANCER SURVIVORS: Qigong may be an effective nonpharmacological intervention for the management of senior prostate cancer survivors' fatigue and distress.


Assuntos
Adenocarcinoma/psicologia , Fadiga/terapia , Neoplasias da Próstata/psicologia , Qigong , Estresse Psicológico/terapia , Sobreviventes/psicologia , Adenocarcinoma/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Etnicidade/psicologia , Fadiga/epidemiologia , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Exercícios de Alongamento Muscular , Cooperação do Paciente , Neoplasias da Próstata/epidemiologia , Qualidade de Vida , Fatores Socioeconômicos , Estresse Psicológico/epidemiologia , Utah/epidemiologia
17.
Ayu ; 35(4): 391-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26195901

RESUMO

BACKGROUND: India leads the world with maximum number of diabetes patients being termed as the "diabetes capital of the world." Certain risk factors including unsatisfactory diet, overweight, and a sedentary lifestyle are potentially reversible. Acharayas have widely described the role of diet and activities to control Madhumeha (type 2 diabetes mellitus [T2DM]) along with medications. Habitual consumption of roasted or dry Barley (Hordeum vulgare L.) flour, Mudga (Phaseolus aureus Roxb.) and Amalaki (Emblica officinalis Gaertn.) prevents the manifestation of Prameha. AIM: To assess the clinical effects of dietary interventions and life style modifications in Madhumeha patients. MATERIALS AND METHODS: Present study was carried out on 56 patients of Madhumeha from S.S. Hospital, Banaras Hindu University, Varanasi. Dietary interventions and life style modifications schedule was prepared based on Ayurvedic principles and patients were advised to follow this regimen. Three consecutive follow-ups were done for 3 months at the interval of one month each. RESULTS: Significant improvement was observed in clinical signs and symptoms along with plasma glucose and glycosylated hemoglobin (HbA1c) in Madhumeha patients after these interventions (P < 0.001). CONCLUSION: Dietary interventions and life style modifications are two important tools by which adequate glycemic control can be obtained, especially in newly diagnosed T2DM patients and in patients who are on antidiabetic medication, but not properly controlled.

18.
Integr Cancer Ther ; 12(6): 464-74, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23620504

RESUMO

OBJECTIVE: The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL). DESIGN: This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control. METHODS: Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants' qualitative feedback on the intervention. RESULTS: Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received. CONCLUSION: The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.


Assuntos
Neoplasias da Mama/psicologia , Satisfação do Paciente , Qualidade de Vida , Tai Chi Chuan , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cooperação do Paciente , Apoio Social , Sobreviventes
19.
Acta Haematol ; 122(2-3): 103-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19907147

RESUMO

Mild-to-moderate anemia often develops in the setting of acute or chronic immune activation and is termed anemia of chronic disease (ACD) or anemia of inflammation. Anemia of chronic disease is the second most common type of anemia (after anemia of iron deficiency) and results in increased morbidity and mortality of the underlying disease. Anemia of chronic disease is mediated by inflammatory cytokines and is characterized by low serum iron (hypoferremia) and often increased reticuloendothelial stores of iron. Hepcidin is the master regulator of iron homeostasis and its synthesis is inhibited by iron deficiency and stimulated by inflammation. The serum hepcidin level is useful in identifying iron deficiency in patients with ACD. Successful treatment of the underlying disease improves ACD. If that is not possible and if anemia is symptomatic, treatment with erythropoietic agents, supplemented with iron if necessary, is helpful in many cases.


Assuntos
Anemia/etiologia , Inflamação/complicações , Anemia/fisiopatologia , Anemia/terapia , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/fisiologia , Doença Crônica , Regulação da Expressão Gênica , Hepcidinas , Humanos , Ferro/sangue , Receptores da Transferrina/metabolismo
20.
Indian J Med Sci ; 60(11): 461-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17090867

RESUMO

RESEARCH QUESTION: Whether socio-demographic factors are associated with initiation of breast-feeding in urban slums of Chandigarh. OBJECTIVES: (1) To study the prevailing breast-feeding practices adopted by mothers, (2) To study the socio-demographic factors associated with initiation of breast-feeding. STUDY DESIGN: Cross-sectional. PARTICIPANTS: Mothers of infants willing to participate in the study in the selected area. SAMPLE SIZE: A total of 270 respondents. STUDY VARIABLES: Social and demographic characteristics like age, socioeconomic status, educational level, birth interval, parity, gender preference, natal care practices, etc.; and variables related to various aspects of breast-feeding practices like prelacteal feed, initiation of feeding, colostrum feeding, reasons of discarding colostrum, etc. STATISTICAL ANALYSIS: Chi-square test and odd ratios along with their respective 95% confidence intervals, multiple logistic regression analysis. RESULTS: Out of all 270 respondents, 159 (58.9%) initiated breast-feeding within 6 h of birth, only 43 (15.9%) discarded colostrum and 108 (40.0%) mothers gave prelacteal feed. Illiterate/just literate mothers who delivered at home were found at significantly higher risk of delay in initiation of breast-feeding on the basis of multiple logistic regression analysis. SUGGESTIONS: Promotion of institutional deliveries and imparting health education to mothers for protecting and promoting optimal breast-feeding practices are suggested.


Assuntos
Aleitamento Materno/epidemiologia , Aleitamento Materno/psicologia , Cuidado do Lactente , Áreas de Pobreza , População Urbana , Adulto , Colostro , Estudos Transversais , Cultura , Demografia , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Razão de Chances , Fatores Socioeconômicos
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