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Transgender individuals represent 0.55% of the US population, equivalent to 1.4 million transgender adults. In transgender women, feminisation can include a number of medical and surgical interventions. The main goal is to deprive the phenotypically masculine body of androgens and simultaneously provide oestrogen therapy for feminisation. In gender-confirming surgery (GCS) for transgender females, the prostate is usually not removed. Due to limitations of existing cohort studies, the true incidence of prostate cancer in transgender females is unknown but is thought to be less than the incidence among cis-gender males. It is unclear how prostate cancer develops in androgen-deprived conditions in these patients. Six out of eleven case reports in the literature presented with metastatic disease. It is thought that androgen receptor-mediated mechanisms or tumour-promoting effects of oestrogen may be responsible. Due to the low incidence of prostate cancer identified in transgender women, there is little evidence to drive specific screening recommendations in this patient subpopulation. The treatment of early and locally advanced prostate cancer in these patients warrants an individualised thoughtful approach with input from patients' reconstructive surgeons. Both surgical and radiation treatment for prostate cancer in these patients can profoundly impact the patient's quality of life. In this review, we discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in our knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.
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Neoplasias da Próstata , Pessoas Transgênero , Masculino , Adulto , Humanos , Feminização/tratamento farmacológico , Qualidade de Vida , Detecção Precoce de Câncer , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Estrogênios/uso terapêuticoRESUMO
BACKGROUND: In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC. METHODS: Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment. RESULTS: Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin. CONCLUSION: In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Docetaxel , Neoplasias de Próstata Resistentes à Castração/patologia , Antígeno Prostático Específico , Inibidor Tecidual de Metaloproteinase-1/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
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Carcinoma de Células Renais , Exossomos , Vesículas Extracelulares , Neoplasias Renais , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Carcinoma de Células Renais/patologia , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Relevância Clínica , Neoplasias Renais/metabolismo , Recidiva Local de Neoplasia/patologia , Vesículas Extracelulares/metabolismo , Exossomos/metabolismoRESUMO
Early identification of cognitive impairment would allow affected patients to receive care at earlier stage. Changes in the arterial stiffness have been identified as a prominent pathological feature of dementia. This study aimed to verify if applying machine-learning analysis to spectral indices of the arterial pulse waveform can be used to discriminate different cognitive conditions of community subjects. 3-min Radial arterial blood pressure waveform (BPW) signals were measured noninvasively in 123 subjects. Eight machine-learning algorithms were used to evaluate the following 4 pulse indices for 10 harmonics (total 40 BPW spectral indices): amplitude proportion and its coefficient of variation; phase angle and its standard deviation. Significant differences were noted in the spectral pulse indices between Alzheimer's-disease patients and control subjects. Using them as training data (AUC = 70.32% by threefold cross-validation), a significant correlation (R2 = 0.36) was found between the prediction probability of the test data (comprising community subjects at two sites) and the Mini-Mental-State-Examination score. This finding illustrates possible physiological connection between arterial pulse transmission and cognitive function. The present findings from pulse-wave and machine-learning analyses may be useful for discriminating cognitive condition, and hence in the development of a user-friendly, noninvasive, and rapid method for the early screening of dementia.
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Doença de Alzheimer , Disfunção Cognitiva , Rigidez Vascular , Cognição , Disfunção Cognitiva/diagnóstico , Humanos , Aprendizado de MáquinaRESUMO
BACKGROUND: The most common site of disease in metastatic castration-resistant prostate cancer (mCRPC) is the bone. The ALSYMPCA study demonstrated that radium-223 significantly improved overall survival (OS) in mCRPC patients with symptomatic bone metastases and without visceral metastases. However, administration requires a multidisciplinary approach and an infrastructure that supports coordination of care, which may differ by practice site. We aimed to evaluate practice patterns and treatment outcomes in patients with mCRPC treated at a community practice (CP) compared with those treated at an academic center (AC). METHODS: This retrospective review included 200 adult mCRPC patients receiving radium-223 between January 2014 and June 2017. The primary endpoint, OS, was estimated from the date of radium-223 initiation. Secondary outcomes included a comparison of baseline characteristics, reasons for initiation and discontinuation of radium-223, and treatment sequencing. A subset analysis of OS based on the number of radium-223 doses and on sequencing of radium-223 either before or after chemotherapy was also conducted. RESULTS: Most patients were treated at a CP (57%). Patients treated at CP sites were significantly older (74.9 vs. 71.9 years; p = .031) and had more comorbidities (Klabunde score 1.1 vs. 0.7; p = .020) than those in an AC but initiated treatment within a shorter period of time from diagnosis of mCRPC (1.3 vs. 1.9 years; p < .001) and received a greater mean number of radium-223 doses (5.4 vs. 4.8; p = .001). There were no observed differences in OS between CPs versus ACs (21.6 vs. 20.7 months; p = .306). Overall, patients who received 5-6 doses versus 1-4 doses of radium-223 had a longer median OS (23.3 vs. 6.4 months; p < .001). The most common reason for discontinuation in patients who did not complete treatment was disease progression. Overall, 43% of patients received radium-223 monotherapy and 57% concurrently with other agents. CONCLUSIONS: Most patients received radium-223 concurrently with abiraterone acetate or enzalutamide and were able to complete 5-6 doses of radium-223. Despite differences in the populations and treatment patterns, no survival differences between patients treated in ACs versus CPs were observed. Additional real-world data are needed to validate these findings.
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Centros Médicos Acadêmicos/métodos , Neoplasias Ósseas/radioterapia , Serviços de Saúde Comunitária/métodos , Gerenciamento Clínico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/uso terapêutico , Centros Médicos Acadêmicos/tendências , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Serviços de Saúde Comunitária/tendências , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
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.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Conduta ExpectanteRESUMO
In this study, a rapid, inexpensive and convenient microwave assisted synthesis of indole-3-propionic acid-bisphenol A diglycidyl ether (IPA-SR3) fluorescent probe was developed. This fluorescent probe has the dual illumination characteristics of photoinduced electron transfer and aggregation-induced emission for the specific detection of Cu2+ ion in water. The wavelength-dependent photoluminescence behavior of the aggregated IPA-SR3 was highly selective (Ksv = 1.5 × 104 M-1) and sensitive in Cu2+ ion detection, with a low limit of detection (2.9 µM). Therefore, it can be used to detect low-concentration Cu2+ in water samples. Details of the synthesis procedure and fluorescence characteristics are presented herein. Graphical Abstract.
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There have been more drugs approved by the US Food and Drug Administration for the treatment of castration-resistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from "bench to bedside," the recent successes in the treatment of prostate cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castration-resistant disease are evaluated. This review will explore the shifting paradigm in drug development for castration-resistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease.
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Castração/efeitos adversos , Neoplasias da Próstata/terapia , Androstenos , Androstenóis/farmacologia , Androstenóis/uso terapêutico , Anilidas/farmacologia , Anilidas/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzamidas , Vacinas Anticâncer/farmacologia , Vacinas Anticâncer/uso terapêutico , Ensaios Clínicos como Assunto , Denosumab , Quimioterapia Combinada , Humanos , Masculino , Nitrilas , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ligante RANK/antagonistas & inibidores , Compostos Radiofarmacêuticos/farmacologia , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/farmacologia , Rádio (Elemento)/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Taxoides/farmacologia , Taxoides/uso terapêutico , Extratos de Tecidos/farmacologia , Extratos de Tecidos/uso terapêuticoRESUMO
BACKGROUND/AIMS: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. METHODS: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. RESULTS: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. CONCLUSION: MRE exhibited antiinflammatory and hepatic protective activity.
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Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Flavonoides/uso terapêutico , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Flavonoides/química , Flavonoides/farmacologia , Mediadores da Inflamação/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Morus/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7RESUMO
OPINION STATEMENT: Non-clear cell renal cell carcinoma (RCC) encompasses a diverse group of diseases, with research yielding different histologic findings and genetic profiles with each distinct subgroup. Simply mirroring the management techniques of clear cell RCC and borrowing from its growing armamentarium of therapeutic agents, while somewhat productive at first, but will ultimately be limiting. Further investigation into the molecular pathogenesis of disease, similarities and differences between specific subtypes, and mechanisms of resistance to therapeutics will help identify new targets, stimulate development of novel agents, and improve clinical trial offerings for non-clear cell RCC (nccRCC). As nccRCC has been largely excluded from past trials, there will be a need for future trials to be designed either to evaluate nccRCC specifically, or to include nccRCC as a prespecified subgroup. Multi-center collaborative trials should be supported, as many of the nccRCC subtypes are rare and remain underrepresented even within the construct of trials that only enroll nccRCC. Given the absence of clear molecular targets at present, patients with metastatic nccRCC should be offered and encouraged enrollment on clinical studies whenever possible.
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Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Biomarcadores Tumorais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Gradação de Tumores , Resultado do TratamentoRESUMO
LESSONS LEARNED: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation. BACKGROUND: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC). METHODS: Black men with mCRPC were treated with abiraterone acetate (AA), 1,000 mg daily, and prednisone (P), 5 mg twice daily. The primary objective was to determine antitumor activity (defined by a ≥30% decline in prostate-specific antigen [PSA] level) and to correlate germline polymorphisms in androgen metabolism genes with antitumor activity. Secondary objectives included determining safety, post-treatment changes in measurable disease, and time to disease progression. RESULTS: From April 2013 to March 2016, a total of 11 black men were enrolled and received AA plus P (AA+P); 7 of 10 evaluable patients were docetaxel naive. Post-treatment declines in PSA level of ≥30% were achieved in 90% of patients. The side effect profile was consistent with prior clinical trials exploring AA+P in mCRPC. Due to poor accrual, the study was closed prematurely with insufficient sample size for the planned pharmacogenetic analyses. CONCLUSION: In this small prospective study terminated for poor accrual, the safety and activity of AA+P in black men with mCRPC was similar to that reported in prior studies exploring AA in largely white populations. Further efforts are needed to address underrepresentation of black men in mCRPC trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/administração & dosagem , Acetato de Abiraterona/efeitos adversos , Idoso , População Negra , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/etnologia , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
BACKGROUND: Castration-resistant prostate cancer (CRPC) is associated with wide variations in survival. Recent studies of whole blood mRNA expression-based biomarkers strongly predicted survival but the genes used in these biomarker models were non-overlapping and their relationship was unknown. We developed a biomarker model for CRPC that is robust, but also captures underlying biological processes that drive prostate cancer lethality. METHODS: Using three independent cohorts of CRPC patients, we developed an integrative genomic approach for understanding the biological processes underlying genes associated with cancer progression, constructed a novel four-gene model that captured these changes, and compared the performance of the new model with existing gene models and other clinical parameters. RESULTS: Our analysis revealed striking patterns of myeloid- and lymphoid-specific distribution of genes that were differentially expressed in whole blood mRNA profiles: up-regulated genes in patients with worse survival were overexpressed in myeloid cells, whereas down-regulated genes were noted in lymphocytes. A resulting novel four-gene model showed significant prognostic power independent of known clinical predictors in two independent datasets totaling 90 patients with CRPC, and was superior to the two existing gene models. CONCLUSIONS: Whole blood mRNA profiling provides clinically relevant information in patients with CRPC. Integrative genomic analysis revealed patterns of differential mRNA expression with changes in gene expression in immune cell components which robustly predicted the survival of CRPC patients. The next step would be validation in a cohort of suitable size to quantify the prognostic improvement by the gene score upon the standard set of clinical parameters.
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Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Neoplasias de Próstata Resistentes à Castração/sangue , RNA Mensageiro/sangue , Idoso , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/genéticaRESUMO
PURPOSE: We examined differences in outcome in patients with biopsy Gleason score 8 vs 9-10 who received definitive local therapy. MATERIALS AND METHODS: Using an institutional database we identified a cohort of 847 patients with biopsy Gleason 8-10 disease who received definitive local therapy with radiation therapy or radical prostatectomy between January 2001 and December 2011. Multivariable Cox modeling was used to assess the association of Gleason score 8 vs 9-10 with time to biochemical recurrence, metastasis and overall survival, and evaluate treatment by Gleason score interaction. Median followup in the cohort was 5.3 years. RESULTS: Baseline patient characteristics were similar for biopsy Gleason 8 vs 9-10. Gleason 9-10 disease was associated with higher prostate specific antigen at diagnosis. As local treatment such patients were also more likely to have received radiation therapy (58% vs 46%, p = 0.001) and neoadjuvant/adjuvant androgen deprivation therapy (64% vs 49%, p <0.001). Those with higher grade disease were at increased risk for metastasis (HR 1.41, 95% CI 1.11-1.79). There was a trend toward an increased risk of death in Gleason 9-10 vs 8 cases (HR 1.28, 95% CI 0.98-1.66). The increased risk of death for Gleason 9-10 was mainly observed in patients treated with radical prostatectomy with or without additional radiation therapy (HR 1.74, 95% CI 1.15-2.65). CONCLUSIONS: Patients with localized biopsy Gleason 9-10 disease treated with definitive local therapy had worse outcomes than those diagnosed with biopsy Gleason 8 disease. Clinical trials are urgently needed that incorporate newer approaches to Gleason 9-10 cancer.
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Adenocarcinoma/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/terapia , Humanos , Masculino , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Plasmonic whispering gallery (WG) modes confined in metal-coated resonators are theoretically investigated by electromagnetic analyses. The resonance can be tuned from internal surface plasmonic WG modes to the hybrid state of the plasmonic mode by an introduced isolation layer. As the coated metal is reduced in size, the optical resonance is shifted out by the mode coupling of the internal and external surface plasmonic WG modes. Based on the optical leak of the plasmonic WG mode, the optical influences led by the surroundings with a variable refractive index are considered. Device performance criteria such as optical power leak, resonant wavelength shift, and threshold gain are studied. Full wave simulations are also employed and the results present good consistency with analytic solutions. The metal-coated resonator assisted by an active material is expected to provide promising performance as a refractometric sensor.
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The double transfer matrix method (DTMM) is proposed for calculating the eigenvalues of the resonant mode of a metallically coated dielectric rectangle resonator. Two-dimensional electromagnetic analyses are performed to investigate the optical influences induced by planar structure parameters. The results show that there theoretically exists a highest Q-factor resonance for both TE and TM modes at a certain length-width ratio with fixed resonant wavelength and resonator area. Due to the influence of surface plasma polaritons (SPPs) trapped at the corners of the resonator which is not considered in DTMM, the TM mode resonances are deformed and deviate severely from that of the analytical model. The geometric deformation on the resonator is introduced by replacing the four right angles with circular boundaries, and the SPP accompanied mode behaviors are corrected to the standing waves.
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BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) most commonly metastasizes to the bone, and less commonly to nonosseous sites (eg, lymph nodes, liver, lung). With new therapies extending survival in mCRPC, it was hypothesized that the pattern of metastases is changing over time. The pattern of metastatic disease was evaluated in men with mCRPC, as reported in baseline characteristics of prospective clinical trials over 2 decades. METHODS: This study identified all phase 2 and 3 therapeutic studies in men with mCRPC in PubMed and American Society of Clinical Oncology abstracts from 1990 to 2012. Studies were excluded if they did not report demographic data and sites of metastasis, or excluded patients with a specific site of metastatic disease (except brain). For each type of metastasis, weighted least squares linear regression models were used to evaluate temporal trends. RESULTS: A total of 290 eligible studies (270 phase 2 studies and 20 phase 3 studies) involving 19,110 patients were identified. Between 1990 and 2012, the rate of nonosseous metastasis increased significantly at 1.6% per year (P < .0001), whereas the rate of osseous metastasis decreased at 0.5% per year (P < .0001). The rate of lymph node metastasis increased at 1.4% per year (P < .0001), but the rate of liver and lung metastasis remained relatively stable. CONCLUSIONS: A notable change was found in the pattern of metastasis in patients with mCRPC. Because these evolving patterns may have important implications in treatment selection and prognosis, it is crucial that future clinical trials of patients with mCRPC define patients with a uniform reporting of nonosseous metastasis.
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Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias da Próstata/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Humanos , Incidência , Masculino , Metástase Neoplásica , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
BACKGROUND: Outcomes with current chemotherapy in metastatic urothelial carcinoma (MUC) remain poor. Lenalidomide, an antiangiogenic and immunomodulatory agent, enhances the effects of chemotherapy in preclinical studies. In this phase Ib/II study, we sought to determine a tolerable dose of lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC and to explore the safety and activity of this regimen. METHODS: Patients with chemotherapy-naïve MUC received gemcitabine 1,000 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 1 every 21 days. In phase Ib, there were four planned escalating dose levels of lenalidomide (10, 15, 20, and 25 mg) daily on days 1-14. RESULTS: Seven patients received GCL in phase Ib. The dose of lenalidomide was not escalated beyond 10 mg because of cytopenias requiring repeated dose delays and reductions. Two additional patients were enrolled in phase II, but the study was ultimately terminated due to poor tolerability and slow accrual. The most frequent grade ≥ 3 adverse events were cytopenias and diarrhea. Three of the nine patients experienced an objective response (one complete response, two partial responses). CONCLUSION: Chronic administration of the GCL regimen was poorly tolerated because of additive and cumulative myelosuppression.
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Carcinoma/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Talidomida/análogos & derivados , Urotélio/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/patologia , Desoxicitidina/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Lenalidomida , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Talidomida/administração & dosagem , Urotélio/efeitos dos fármacos , GencitabinaRESUMO
MOTIVATION: The evolutionary history of species is traditionally represented with a rooted phylogenetic tree. Each tree comprises a set of clusters, i.e. subsets of the species that are descended from a common ancestor. When rooted phylogenetic trees are built from several different datasets (e.g. from different genes), the clusters are often conflicting. These conflicting clusters cannot be expressed as a simple phylogenetic tree; however, they can be expressed in a phylogenetic network. Phylogenetic networks are a generalization of phylogenetic trees that can account for processes such as hybridization, horizontal gene transfer and recombination, which are difficult to represent in standard tree-like models of evolutionary histories. There is currently a large body of research aimed at developing appropriate methods for constructing phylogenetic networks from cluster sets. The Cass algorithm can construct a much simpler network than other available methods, but is extremely slow for large datasets or for datasets that need lots of reticulate nodes. The networks constructed by Cass are also greatly dependent on the order of input data, i.e. it generally derives different phylogenetic networks for the same dataset when different input orders are used. RESULTS: In this study, we introduce an improved Cass algorithm, Lnetwork, which can construct a phylogenetic network for a given set of clusters. We show that Lnetwork is significantly faster than Cass and effectively weakens the influence of input data order. Moreover, we show that Lnetwork can construct a much simpler network than most of the other available methods. AVAILABILITY: Lnetwork has been built as a Java software package and is freely available at http://nclab.hit.edu.cn/â¼wangjuan/Lnetwork/. CONTACT: maozuguo@hit.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Filogenia , Software , Algoritmos , Análise por ConglomeradosRESUMO
Objective: This study aimed to evaluate the effectiveness of Qi Gong fitness in alleviating stress, anxiety, and depression among underprivileged working youth with a follow-up study. Methods: Eighty subjects were randomly assigned to normal groups (NG) and treatment groups (TG), with 40 participants in each group. The Perceived Stress Scale (PSS), Generalized Anxiety Disorder 7 (GAD-7), and 24-Item Hamilton Rating Scale for Depression (HAMD-24) were used to evaluate the effect of Qi Gong fitness on alleviating stress, anxiety, and depression symptoms in underprivileged working youth. Results: There was no significant difference in demographic outcome indicators between NG and TG. The main analytic results showed significant differences (P < .05) in the intra- and inter-group comparisons of NG and TG in stress, anxiety, and depression before and after intervention. When compared with prior intervention, NG and TG after intervention showed more favorable scores in PSS, GAD-7, and HAMD-24, among which PSS (NG: 51.61 ± 4.32 vs. 29.80 ± 3.08; TG: 55.21 ± 5.41 vs. 15.85 ± 2.25; P < .01), GAD-7 (NG: 10.83 ± 2.45 vs. 9.85 ± 2.52; TG: 12.23 ± 1.90 vs. 7.84 ± 1.57; P < .01), and HAMD-24 (NG: 10.83 ± 2.45 vs. 9.85 ± 2.52; TG: 25.63 ± 3.94 vs. 11.40 ± 3.82; P < .01); These results indicate that NG and TG have significant effects on alleviating occupational stress, anxiety, and depression in young underprivileged people. Conclusion: The study indicates that Qi Gong fitness had a positive effect on reducing and alleviating stress, anxiety, and depression among young underprivileged professionals. This highlights the potential benefits of incorporating Qi Gong fitness into treatment plans.
RESUMO
PURPOSE: Non-obstructive azoospermia (NOA) is a severe and common cause of male infertility. Currently, the most reliable predictor of sperm retrieval success in NOA is histopathology, but preoperative testicular biopsy often increases the difficulty of sperm retrieval surgery. This study aims to explore the characteristics of N6-methyladenosine (m6A) modification in NOA patients and investigate the potential biomarkers and molecular mechanisms for pathological diagnosis and treatment of NOA using m6A-related genes. METHODS: NOA-related datasets were downloaded from the GEO database. Based on the results of LASSO regression analysis, a prediction model was established from differentially expressed m6A-related genes, and the predictive performance of the model was evaluated using ROC curves. Cluster analysis was performed based on differentially expressed m6A-related genes to evaluate the differences in different m6A modification patterns in terms of differentially expressed genes (DEGs), biological features, and immune features. RESULTS: There were significant differences in eight m6A-related genes between NOA samples and healthy controls. The ROC curves showed excellent predictive performance for the diagnostic models constructed with ALKBH5 and FTO. DEGs of two m6A modification subtypes indicated the influence of m6A-related genes in the biological processes of mitosis and meiosis in NOA patients, and there were significant immune differences between the two subtypes. CONCLUSION: The NOA pathological diagnostic models constructed with FTO and ALKBH5 have good predictive ability. We have identified two different m6A modification subtypes, which may help predict sperm retrieval success rate and treatment selection in NOA patients.