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2.
Artigo em Inglês | MEDLINE | ID: mdl-34769545

RESUMO

This study examined the effects of a non-caffeinated energy drink (ED) that contained calamansi juice, glucose, and taurine on 3-km running performance and recovery. Eleven NCAA Division I middle-distance runners (20.8 ± 1.5 years old) were randomly assigned to consume either the ED or a placebo drink 60 min before 3-km running on a 400-m official track. Performance time and speed were recorded every 500-m interval. Recovery blood lactate concentration (BLC), systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured at baseline, 60-min after ingesting the drinks, and post-running measurements were performed at 1-min, 5-min, and 10-min. Repeated analysis of variance and paired t-test were applied to examine the effects of time, trials, and their interaction on performance and recovery. Statistical significance was set a priori at p < 0.05. No significant difference was observed in performance time and speed between trials (p < 0.05). No interaction effect was found on performance time, speed, recovery BLC, DBP, and HR (p < 0.05). However, an interaction effect for trial by time was observed on SBP (p = 0.01). Recovery SBP continues to decrease from 5-min to 10-min in the ED trial (∆ = -13.9 mmHg) and slightly increased in the placebo trial (∆ = 1.1 mmHg). This study suggests that acute consumption of a calamansi-containing ED can positively impact the SBP recovery but not running performance. Further studies are needed to examine the acute and chronic effects of this ED on exercise performance and recovery among different populations.


Assuntos
Desempenho Atlético , Bebidas Energéticas , Corrida , Cafeína , Estudos Cross-Over , Método Duplo-Cego , Frequência Cardíaca
3.
J Neurogastroenterol Motil ; 27(4): 453-481, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34642267

RESUMO

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

4.
Br J Surg ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34718433

RESUMO

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34682598

RESUMO

The present study examines the association between physical activity (PA) participation modes (i.e., family, friends, club members, and alone), PA volumes (i.e., intensity and duration), gender, and injury. A total of 9000 Koreans aged 10-89 years participated in the Korean Survey of Citizens' Sports Participation project. However, participants who did not respond to a question regarding PA participation modes (n = 2429) and those under 18 years old (n = 489) were excluded from this study. Analysis of variance (ANOVA) was used to compare the groups' characteristics and the association between PA participation modes and injury was demonstrated by conducting multinomial logistic regression analysis. The risk of injury was significantly higher in the friend and club member groups than in the alone group. In addition, PA intensity and gender were critical risk factors of injury, while PA duration showed no significant results. The results indicated a strong association between PA participation modes, PA intensity, gender, and injury, and an interesting finding is that more injuries derived from a higher intensity of PA, not from a longer duration of PA. Therefore, this present study directly documented that considerable attention should be placed on the factors that affect injuries, such as gender and PA intensity, to prevent unpredictable injury and encourage potential participants to exercise with diverse participation modes and appropriate intensity.


Assuntos
Exercício Físico , Esportes , Adolescente , Identidade de Gênero , Humanos , Fatores de Risco , Inquéritos e Questionários
7.
Expert Rev Hematol ; 14(9): 819-830, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34375536

RESUMO

INTRODUCTION: Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy. AREAS COVERED: The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism. EXPERT OPINION: Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.


Assuntos
Adenina/análogos & derivados , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adenina/efeitos adversos , Adenina/farmacologia , Adenina/uso terapêutico , Idoso , COVID-19/complicações , Gerenciamento Clínico , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia
8.
Ann Hepatobiliary Pancreat Surg ; 25(3): 349-357, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34402435

RESUMO

Backgrounds/Aims: Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents. Methods: Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively. Results: Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies. Conclusions: Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.

9.
Expert Rev Hematol ; 14(8): 765-775, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34313508

RESUMO

INTRODUCTION: The long-term survival of relapsed/refractory (R/R) adult T-cell acute lymphoblastic leukemia (T-ALL) is quite poor, and early T-cell precursor (ETP) ALL has recently been described as a high-risk T-ALL subgroup. However, the optimal therapeutic approach to R/R adult T-ALL remains poorly established. AREAS COVERED: At present, cytoreductive therapy followed by allogeneic stem cell transplantation (allo-SCT) is considered to be the most clinically relevant and curative modality for R/R T-ALL. Above all, achieving minimal residual disease (MRD) is a key factor for successful allo-SCT and maintaining long-term remission for R/R patients. As a salvage regimen, nelarabine is the only therapy that was specifically approved for use in patients with R/R T-ALL. A combination of conventional chemotherapeutic agents and novel agents, such as venetoclax, can be used as alternatives for cytoreduction and bridging to transplantation. Relevant literatures published in the last 30 years were searched from PubMed to review the topic of T-ALL, and allo-SCT. EXPERT OPINION: An effective salvage regimen, to achieve negative MRD, followed by allo-SCT is currently the best way to improve the clinical outcomes of adult R/R T-ALL. Moreover, posttransplant therapies, such as prophylactic or preemptive donor leukocyte infusion and hypomethylating agents, need to be considered as sequential therapy.

10.
Nat Commun ; 12(1): 4194, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234144

RESUMO

Photomorphogenesis, light-mediated development, is an essential feature of all terrestrial plants. While chloroplast development and brassinosteroid (BR) signaling are known players in photomorphogenesis, proteins that regulate both pathways have yet to be identified. Here we report that DE-ETIOLATION IN THE DARK AND YELLOWING IN THE LIGHT (DAY), a membrane protein containing DnaJ-like domain, plays a dual-role in photomorphogenesis by stabilizing the BR receptor, BRI1, as well as a key enzyme in chlorophyll biosynthesis, POR. DAY localizes to both the endomembrane and chloroplasts via its first transmembrane domain and chloroplast transit peptide, respectively, and interacts with BRI1 and POR in their respective subcellular compartments. Using genetic analysis, we show that DAY acts independently on BR signaling and chlorophyll biogenesis. Collectively, this work uncovers DAY as a factor that simultaneously regulates BR signaling and chloroplast development, revealing a key regulator of photomorphogenesis that acts across cell compartments.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Membrana/metabolismo , Morfogênese/fisiologia , Proteínas Quinases/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Brassinosteroides/metabolismo , Clorofila/biossíntese , Cloroplastos/metabolismo , Estiolamento/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/isolamento & purificação , Luz , Proteínas de Membrana/genética , Proteínas de Membrana/isolamento & purificação , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Morfogênese/efeitos da radiação , Mutação , Plantas Geneticamente Modificadas , Proteínas Quinases/genética , RNA-Seq , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Plântula/crescimento & desenvolvimento , Transdução de Sinais/fisiologia
11.
Case Rep Oncol ; 14(2): 998-1003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326734

RESUMO

Although testicular germ cell tumors (GCTs) are known to curable disease even in cases with metastatic disease, patients in intermediate or poor-risk group may experience disease progression or refractory to the initial chemotherapy and needed second-line therapy. Long-term disease-free survival was unsatisfactory in relapsed/refractory patients with poor-risk factors and clinical trials for those patients are still insufficient. High-dose chemotherapy (HDCT) with stem-cell rescue may be an effective alternative for conventional chemotherapy-resistant patients who are eligible for transplantation. Herein, we present successful treatment experience with HDCT followed by autologous stem-cell transplantation in a severely ill patient with heavily pretreated metastatic GCT.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34299707

RESUMO

The current study is to examine the differences in physical activity (PA), sedentary behavior (SB), and mental health (i.e., stress, depression, and suicidal behaviors) between early menopausal women and age-matched general middle-aged women. Among 1348 participants in South Korea, 674 participants who experienced menopause before the age of 45 were defined as the early menopausal group, and 674 women who experienced menopause from 45 years to 55 years were classified as the general group by matching age based on early menopausal women. PA, SB, and mental health were evaluated by using the Global Physical Activity Questionnaire (GPAQ). An independent t-test was used to compare the associations of PA, SB, and mental health between the two groups. To demonstrate the predictors of early menopause, variables in the study were analyzed by multinomial logistic regression. The main findings were that moderate-to-vigorous PA (MVPA) and light PA (LPA) had significant differences between the two groups, but SB had no significant differences. In mental health, only perceived stress had significant differences in this study. The moderate level of stress in the early menopausal group was twice as high as that of the general group, and the severe level of stress was even 2.6 times higher than the general group. PA plays an essential role in mitigating the causes of mortality and the risk of various chronic diseases and improving quality of life; thus, the main findings of this study could be important to provide insights on the corresponding impact between early menopausal women and PA to encourage their healthy lifestyle. Further longitudinal studies are needed to examine the mechanisms underlying the effects of PA, SB, and mental health on early menopausal women.


Assuntos
Saúde Mental , Comportamento Sedentário , Acelerometria , Exercício Físico , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Qualidade de Vida
13.
Artigo em Inglês | MEDLINE | ID: mdl-34205703

RESUMO

The current study examined the differences in health-related physical fitness (HRPF), physical activity (PA), and sedentary behavior (SB) between adolescents with and without ongoing respiratory diseases (RD). This study's participants were from 12 to 15 years old (7th-10th grade) in South Korea. Adolescents with RD were selected through RD-related questions (i.e., asthma, rhinitis, sinusitis, and bronchitis) (n = 139); in contrast, adolescents without RD, randomly selected from the general group, responded to any health problem-related questions as "No" (n = 139). HRPF was measured based on the FITNESSGRAM and EURO FIT test batteries and the measurements of HRPF included cardiovascular endurance, muscular strength, muscular endurance, flexibility, and body composition. All statistical analyses were conducted by SPSS 25.0, and the independent t-test was used to compare the HRPF and PA between the two groups. Moreover, the measured HRPF was compared with a series of analyses of three-way ANOVAs (age × gender × group). Adolescents with RD had a positive association with less participation in PA (p < 0.05; RD: 3081.81 ± 4793.37; general: 2073.64 ± 3123.47) and with more time spent on SB (above 12 h per week: RD group (38.85%) and general group (33.09%)). Furthermore, adolescents in the RD group showed significant effects on all components of HRPF (p < 0.05). Our study confirmed that HRPF is an essential predictor of adolescents' health outcomes, especially for those with RD. We suggest that increased HRPF can be an effective treatment for respiratory diseases in adolescents, and health practitioners should pay more attention to helping adolescents with RD to gain or maintain high HRPF.


Assuntos
Aptidão Física , Comportamento Sedentário , Adolescente , Criança , Exercício Físico , Humanos , Força Muscular , República da Coreia/epidemiologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-34201810

RESUMO

This study examined the effects of resistance training on muscle quality, muscle growth factors, and functional fitness in older adult women with sarcopenia. Twenty-two older adult women aged over 65 with sarcopenia were randomly assigned to either resistance training (RT, n = 12) or non-exercise control group (CG, n = 10). The body weight-based and elastic band RT were performed three times a week, 60 min per session, for 16 weeks. Body composition and thigh muscle quality were estimated by dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT), respectively. The muscle growth factors, including growth differentiation factor-8 (GDF-8), growth differentiation factor-15 (GDF-15), activin A, and follistatin, were analyzed via blood samples. Statistical analyses were performed using repeated measures multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), and effect size (i.e., cohen's d, partial eta square), and the significance level was set at 0.05. The RT group improved their functional fitness, grip strength, gait speed, and isometric muscle strength (p < 0.01, d > 0.99; large), while these variables did not change in the CG. An increase in intramuscular fat was only observed in the CG (p < 0.01, 1.06; large). Muscle growth factors such as follistatin were significantly increased in the RT (p < 0.05, 0.81; large), but other variables did not change following resistance training. Sixteen weeks of resistance training improved functional fitness and prevented age-related increases in intramuscular fat in the thigh area. However, there were only some changes in muscle growth factors, such as follistatin, suggesting that the effectiveness of resistance training on muscle growth factors is limited. Body weight-based and elastic band resistance training is an alternative training method for sarcopenia to minimize the age-related adverse effects on muscle function and quality.


Assuntos
Treinamento de Força , Sarcopenia , Idoso , Composição Corporal , Exercício Físico , Feminino , Humanos , Força Muscular , Músculo Esquelético/metabolismo
15.
Nat Commun ; 12(1): 3880, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162872

RESUMO

Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Receptor Notch1/genética , Transdução de Sinais/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia , Receptor Notch1/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-34072563

RESUMO

The purpose of the current study is to investigate the changes in physical activity (PA), sleep time (ST), and body weight (BW) Pre- and during COVID-19 in South Korea, and specifically, PA data were obtained during COVID-19 at three-time points based on the multilevel social distancing policies. All data were surveyed by questionnaires online and offline, and participants were required to fill in the monthly average of daily step counts were recorded an application on participants' smartphone devices from Pre-COVID-19 (2019 year) and during COVID-19 (2020 year). Participants were 834 adults (males: 54.4%, female: 45.6%) and all statistical analyses were summarized by SPSS 25.0 program. The monthly average of daily step counts was 6747.09 during Pre-COVID-19, but the PA during COVID-19 was 5812.11 daily step counts per month. Also, there were significant pairwise differences between average PA Pre-COVID-19 and each level of social distancing (p < 0.001). After COVID-19, the participants who slept less than 7 hours decreased by 3.6%, while those who slept more than 9 hours increased by that much. As a result of BW, 269 participants responded their BW changed during COVID-19, and 199 of them reported they gained BW during COVID-19 (74.0%). Although self-reported questionnaires may have led to an under-or over-estimation of ST and BW, the present study found that the environment in which the COVID-19 is prevalent had adverse relationships on PA, ST, and BW. Therefore, it is important to identify strategies to motivate individuals for remaining physically active and getting adequate sleep while maintaining social distancing due to the presence of the COVID-19 global pandemic.


Assuntos
COVID-19 , Adulto , Peso Corporal , Exercício Físico , Feminino , Humanos , Masculino , República da Coreia , SARS-CoV-2 , Sono
17.
Ann Surg Treat Res ; 100(6): 320-328, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34136428

RESUMO

Purpose: Laparoscopic distal pancreatectomy (LDP) is widely performed but its efficacy and safety are not established for malignant lesions. This study was aimed to compare outcomes of LDP and open distal pancreatectomy (ODP) in pancreatic ductal adenocarcinoma (PDAC). Methods: Patients who underwent distal pancreatectomy for PDAC between 2009 and 2017 were enrolled. The preoperative clinical stage was evaluated and propensity score matching (PSM) was performed using age, sex, The American Joint Committee on Cancer 8th clinical T stage, and other organ involvement. Results: In 186 patients enrolled, 35 (18.8%) received LDP. The ODP group showed larger tumor size and frequent involvement of other organs in preoperative images. However, after PSM, these differences were balanced. R0 resection (90.5% vs. 94.3%, P = 0.730), harvested lymph nodes (14.3 vs. 12.6, P = 0.380) and pathologic T stage (P = 0.474) were comparable between ODP and LDP groups, respectively. LDP demonstrated shorter operation time, less postoperative pain, and shorter hospitalization (14.4 days vs. 11.1 days, P = 0.026). In terms of long-term oncologic outcomes, median overall survival (32 months vs. 28 months, P = 0.724) and disease-free survival (18 months vs. 19 months, P = 0.926) were comparable. Conclusion: LDP demonstrated better short-term outcomes and comparable long-term outcomes compared with ODP. LDP is a safe and feasible procedure for PDAC.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34116956

RESUMO

BACKGROUND: Anaplastic prostate cancer has a poor prognosis with limited treatment options. Seven clinical features of anaplastic prostate cancer have been prospectively identified. In this phase II clinical trial, we identified mutations, including DNA damage repair (DDR) mutations, in patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated with durvalumab and olaparib and determined how many of them can be described as anaplastic, and we examined the overlap between anaplastic features and DDR mutations. METHODS: Eligible patients with mCRPC received prior enzalutamide, abiraterone, or both. Patients were treated with durvalumab 1500 mg i.v. every 28 days and olaparib 300 mg p.o. every 12 hours until disease progression or unacceptable toxicity. Patients underwent mandatory baseline biopsies of metastatic lesions. RESULTS: Baseline characteristics were similar between anaplastic and nonanaplastic patients. Eleven patients (20%) displayed clear anaplastic features, and 43 (78.2%) lacked anaplastic features. In the anaplastic group, 2/11 (18.2%) had germline DRR mutations, and 4/11 (36.3%) had somatic DDR mutations. In the nonanaplastic group, 7/43 (16.3%) had germline mutations, and 13/43 (30.2%) had somatic mutations. Median progression-free survival (PFS) times in patients with anaplastic features (6.5 months) and without anaplastic features (5.1 months) were similar (hazard ratio 0.998, P = .996). CONCLUSIONS: Patients with and without anaplastic features appear to have similar total rates of DDR mutations and also similar rates of somatic and germline DDR mutations. Patients with anaplastic features have a trend toward improved PFS when treated with olaparib and durvalumab compared with nonanaplastic patients.

19.
Cancer Treat Rev ; 98: 102224, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051628

RESUMO

Ovarian cancer is a deadly malignancy with a growing therapeutic armamentarium, though achieving sustained benefit in the clinic remains largely elusive. Through biomarker and genetic analysis, several pathways of resistance and sensitivity to commonly used therapeutics have been identified, expanding the potential of identifying unique drug combinations and indicating new directions for improving clinical outcomes. Here, we review the mechanisms of angiogenic response and antiangiogenic therapy in ovarian cancer, as well as the interactions it exhibits with the immune and DNA damage response pathways. We discuss results from clinical trials examining the combinations of antiangiogenics, PARP inhibitors, and immune checkpoint inhibitors are also discussed, as well as several ongoing trials.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia de Alvo Molecular , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Neovascularização Patológica/patologia , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia
20.
Blood Res ; 56(2): 65-71, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34031277

RESUMO

Background: We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. Methods: We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. Results: Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P=0.053) and overall survival (OS) (P=0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P=0.033). Conclusion: We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

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