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1.
Ann Palliat Med ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34498475

RESUMO

BACKGROUND: We investigated the feasibility and safety of an exercise intervention in patients with metastatic solid cancer. METHODS: Patients scheduled to receive first-line chemotherapy for metastatic cancer with a life expectancy of ≥4 months, no brain metastases, and no high risk of fracture were recruited to participate in a 12-week, combined resistance and aerobic exercise program consisting of supervised, hospital-based (2×/week) and home-based training (3×/week) during palliative chemotherapy. Feasibility and safety of the exercise intervention were the primary outcomes. The secondary outcomes were skeletal muscle mass and strength, functional capacity, quality of life (QoL), and fatigue. RESULTS: Nineteen patients were enrolled in this pilot study. Five patients withdrew consent before the exercise intervention due to fear of exacerbating cancer-related symptoms (n=2), transportation issues (n=2), and unknown reasons (n=1). Ten patients (71.4%) completed the 12-week exercise program. Mean attendance rate of the supervised exercise sessions was 64.9% (range, 16.7-95.8%). No adverse events or skeletal complications occurred during the supervised exercise sessions. Among participants, there were no significant changes in muscle area at the third lumbar level (mean change=-0.7 cm2 , P=0.869) or appendicular skeletal muscle mass (mean change=0.1 kg, P=0.661). The overall QoL assessed using the Functional Assessment of Cancer Therapy-General significantly improved post-exercise interventions (P=0.037). There were significant improvements in the QoL subdomains of emotional well-being and physical, social, and cognitive functions. CONCLUSIONS: Exercise interventions are feasible and safe in patients with metastatic cancer. Exercise interventions can improve QoL and prevent skeletal muscle loss during palliative chemotherapy.

2.
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
3.
Cancer Res Treat ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33940788

RESUMO

Purpose: Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy. Materials and Methods: Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments. Results: Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio [HR] 4.52, 95% confidence interval [CI] 2.32-8.81, p<0.001). Among IC-responders, 84% subsequently received definitive chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%). Conclusion: Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multi-disciplinary approach was warranted reflecting patients' preference, morbidity, and prognosis.

4.
Thorac Cancer ; 12(11): 1662-1667, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33829665

RESUMO

BACKGROUND: Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC). METHODS: This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross-sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2 /m2 in men and < 29 cm2 /m2 in women. RESULTS: The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9-11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2 /month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001). CONCLUSIONS: Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life.

5.
Nature ; 592(7852): 110-115, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33692545

RESUMO

The plant immune system involves cell-surface receptors that detect intercellular pathogen-derived molecules, and intracellular receptors that activate immunity upon detection of pathogen-secreted effector proteins that act inside the plant cell. Immunity mediated by surface receptors has been extensively studied1, but that mediated by intracellular receptors has rarely been investigated in the absence of surface-receptor-mediated immunity. Furthermore, interactions between these two immune pathways are poorly understood. Here, by activating intracellular receptors without inducing surface-receptor-mediated immunity, we analyse interactions between these two distinct immune systems in Arabidopsis. Pathogen recognition by surface receptors activates multiple protein kinases and NADPH oxidases, and we find that intracellular receptors primarily potentiate the activation of these proteins by increasing their abundance through several mechanisms. Likewise, the hypersensitive response that depends on intracellular receptors is strongly enhanced by the activation of surface receptors. Activation of either immune system alone is insufficient to provide effective resistance against the bacterial pathogen Pseudomonas syringae. Thus, immune pathways activated by cell-surface and intracellular receptors in plants mutually potentiate to activate strong defences against pathogens. These findings reshape our understanding of plant immunity and have broad implications for crop improvement.


Assuntos
Arabidopsis/imunologia , Proteínas NLR/imunologia , Imunidade Vegetal/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Arabidopsis/citologia , Arabidopsis/microbiologia , Morte Celular , NADPH Oxidases/metabolismo , Células Vegetais/imunologia , Células Vegetais/microbiologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Proteínas Quinases/metabolismo , Pseudomonas fluorescens/imunologia , Pseudomonas syringae/imunologia , Pseudomonas syringae/patogenicidade , Transdução de Sinais/imunologia
6.
Am J Clin Oncol ; 44(6): 232-238, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710139

RESUMO

OBJECTIVES: Trastuzumab is used as an agent against human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). The aim of this study was to determine how HER2 gene amplification and neutrophil-to-lymphocyte ratio (NLR) could predict long-term survival in AGC patients that underwent trastuzumab-based chemotherapy. METHODS: We retrospectively reviewed medical records of 112 patients between 28 and 91 years old (median of 66 y) with AGC treated with first-line trastuzumab-based chemotherapy. The level of HER2 gene amplification was determined by the HER2/centromere enumerator probe 17 (CEP17) ratio and HER2 gene copy number (GCN). NLR was calculated as the neutrophil count divided by the lymphocyte counts. RESULTS: Median HER2/CEP17 ratio, HER2 GCN, and NLR values were 2.85, 7.1, and 2.81, respectively. Objective response rate in both high HER2/CEP17 ratio (59.4% vs. 28.1%, P=0.012) and HER2 GCN groups (62.1% vs. 33.3%, P=0.032) was higher than that of each group. High NLR correlated with significantly worse median overall survival (OS) (median OS, 8.2 vs. 18.9 mo, P=0.002) and progression free survival (PFS) (median PFS: 5.1 vs. 8.0 mo, P=0.005). However, median OS and PFS were not significantly different according to HER2/CEP17 ratio or HER2 GCN. In the multivariate analysis, high NLR, Eastern Cooperative Group performance status, and poorly differentiated/signet ring cell type were independent factors for OS. CONCLUSIONS: NLR was a significant predictor of long-term survival in AGC patients treated with first-line trastuzumab-based chemotherapy. Future validation of prospective trials with larger patient populations will be needed.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Amplificação de Genes , Linfócitos/patologia , Neutrófilos/patologia , Receptor ErbB-2/genética , Neoplasias Gástricas/mortalidade , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Taxa de Sobrevida
7.
Cancer Res Treat ; 53(4): 1004-1014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33540495

RESUMO

PURPOSE: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea. Materials and Methods: Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals. RESULTS: Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001). CONCLUSION: In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

8.
J Cancer Res Clin Oncol ; 147(8): 2459-2469, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33523301

RESUMO

PURPOSE: Although immune-checkpoint inhibitors have become a new therapeutic option for recurrent/metastatic non-small cell lung cancers (R/M-NSCLC), its clinical benefit in the real-world is still unclear. METHODS: We investigated 1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive [tumor proportion score (TPS) ≥ 10% by the SP263 assay or ≥ 50% by the 22C3 assay] R/M-NSCLC treated with pembrolizumab or nivolumab after failure of platinum-based chemotherapy. RESULTS: The median age was 67 years, 13% of patients had ECOG-PS ≥ 2, and 27% were never-smokers. Adenocarcinoma was predominant (61%) and 18.1% harbored an EGFR activating mutation or ALK rearrangement. Pembrolizumab and nivolumab were administered to 51.3% and 48.7, respectively, and 42% received them beyond the third-line chemotherapy. Objective response rate (ORR) was 28.6%. Pembrolizumab group showed numerically higher ORR (30.7%) than the nivolumab group (26.4%), but it was comparable with that of the nivolumab group having PD-L1 TPS ≥ 50% (32.4%). Median progression-free survival (PFS) and overall survival (OS) were 2.9 (95% CI 0-27.9) and 10.7 months (95% CI 0-28.2), respectively. In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes. CONCLUSION: The real-world benefit of later-line anti-PD1 antibodies was comparable to clinical trials in patients with R/M-NSCLC, although patients generally were more heavily pretreated and had poorer ECOG-PS. Concordantly high PD-L1 TPS ≥ 50% and development of irAE could independently predict better treatment outcomes, while EGFR mutation negatively affected OS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Nivolumabe/uso terapêutico , Prognóstico , República da Coreia/epidemiologia , Análise de Sobrevida , Resultado do Tratamento
9.
Support Care Cancer ; 29(1): 525-531, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32415383

RESUMO

PURPOSE: Our study aimed to evaluate the association between CDS and survival time using the likelihood of receiving CDS to select a matched non-CDS group through an accurate measurement of survival time based on initiation of CDS. METHODS: A retrospective cohort study was performed using an electronic database to collect data regarding terminally ill cancer patients admitted to a specialized palliative care unit from January 2012 to December 2016. We first used a Cox proportional hazard model with receiving CDS as the outcome to identify individuals with the highest plausibility of receiving CDS among the non-CDS group (n = 663). We then performed a multiple regression analysis comparing the CDS group (n = 311) and weighted non-CDS group (n = 311), using initiation of CDS (actual for the CDS group; estimated for the non-CDS group) as the starting time-point for measuring survival time. RESULTS: Approximately 32% of participants received CDS. The most common indications were delirium or agitation (58.2%), intractable pain (28.9%), and dyspnea (10.6%). Final multiple regression analysis revealed that survival time was longer in the CDS group than in the non-CDS group (Exp(ß), 1.41; P < 0.001). Longer survival with CDS was more prominent in females, patients with renal dysfunction, and individuals with low C-reactive protein (CRP) or ferritin, compared with their counterpart subgroup. CONCLUSIONS: CDS was not associated with shortened survival; instead, it was associated with longer survival in our terminally ill cancer patients. Further studies in other populations are required to confirm or refute these findings.


Assuntos
Sedação Profunda/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Neoplasias/mortalidade , Cuidados Paliativos/métodos , Doente Terminal/estatística & dados numéricos , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
Cancer Res Treat ; 53(3): 695-702, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33332933

RESUMO

PURPOSE: YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. MATERIALS AND METHODS: Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. RESULTS: In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. CONCLUSION: This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2- MBC patients irrespective of tamoxifen sensitivity.

11.
Cancers (Basel) ; 12(11)2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33167305

RESUMO

In the era of CDK4/6 inhibitors in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, few trials have been specifically studied to compare quality of life between palbociclib plus endocrine therapy (ET) and cytotoxic chemotherapy exclusively in premenopausal women. We aimed to evaluate differences of patient report outcomes (PROs) between palbociclib plus ET and capecitabine. PROs were assessed using EORTC QLQ-C30 at baseline, every 6 weeks, and the end of treatment. All EORTC QLQ-30 scores were maintained from baseline to the end of treatment. Patients treated palbociclib plus ET arm experienced delay in time-to-deterioration of physical functioning (HR = 0.58, 95% CI, 0.36 to 0.84, p = 0.0058), nausea and vomiting (HR = 0.48; 95% CI, 0.32 to 0.73, p = 0.0005), and diarrhea (HR = 0.42; 95% CI, 0.27 to 0.65, p = 0.001). There was a numeric trend for worsening of insomnia (HR = 1.43; 95% CI, 0.96 to 2.16, p = 0.079) and favoring of appetite loss (HR = 0.69, 95% CI, 0.44 to 1.07, p = 0.09) in the palbociclib plus ET arm. Premenopausal patients with palbociclib plus ET maintained QoL without compromising treatment efficacy.

12.
PLoS One ; 15(10): e0240084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052943

RESUMO

This study aimed to investigate the diagnostic performance of chest computed tomography (CT) for opportunistic screening and longitudinal follow-up of osteoporosis in breast cancer patients, compared to dual-energy X-ray absorptiometry (DXA). The association between L1 vertebral attenuation on chest CT and incidental fracture was also evaluated. We retrospectively reviewed 414 consecutive breast cancer patients who underwent both non-enhanced chest CT and DXA within a 3-month interval and had at least two DXA and two chest CT examinations over more than 1 year. The attenuation value of the L1 trabecular bone was measured on an axial CT image and compared to the corresponding DXA T-score. The diagnostic performance of L1 vertebral attenuation on CT for osteoporosis was calculated at different thresholds (90 HU, 100 HU, 110 HU), and the correlation between L1 vertebral attenuation values and DXA T-scores was statistically analyzed. Overall fracture-free survival was estimated and compared with the threshold of 90 HU on CT and -2.5 T-score on DXA. Of 414 patients (median age, 53.0 years), 88 (21.3%) had either vertebral or non-vertebral fractures. The median follow-up duration between initial and final DXA was 902.9 days. There was a moderate correlation between L1 vertebral attenuation value and DXA T-score (ρ = 0.684, CI 0.653-0.712). Fracture-free survival was significantly lower in patients with attenuation values ≤90 HU on CT and T-scores ≤-2.5 on DXA (P < .001). Multivariate analysis revealed that attenuation values ≤90 HU on CT (P < .001), T-scores ≤-2.5 on DXA (P = .003), and age ≥65 years (P = .03) were independent significant prognostic factors associated with overall fracture-free survival. The sensitivities and specificities of L1 attenuation value were 54.9% and 85.8% at 90-HU threshold, 74.0% and78.4% at 100-HU threshold, and 83.9% and 70.1% at 110-HU threshold, respectively. In conclusion, CT can be used for predicting osteoporosis and discriminating incidental fracture risk in breast cancer patients.


Assuntos
Neoplasias da Mama/patologia , Osteoporose/diagnóstico , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Pessoa de Meia-Idade , Osteoporose/complicações , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico
13.
BMC Cancer ; 20(1): 813, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854649

RESUMO

BACKGROUND: By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. METHODS: This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. RESULTS: A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24-89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). CONCLUSIONS: In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/uso terapêutico , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Terapia Combinada/métodos , Docetaxel/uso terapêutico , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimioterapia de Indução/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Taxa de Sobrevida , Adulto Jovem
14.
Cell Host Microbe ; 27(5): 769-781.e6, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32234500

RESUMO

The Arabidopsis immune receptors RPS4 and RRS1 interact to co-confer responsiveness to bacterial effectors. The RRS1-R allele, with RPS4, responds to AvrRps4 and PopP2, whereas RRS1-S responds only to AvrRps4. Here, we show that the C terminus of RRS1-R but not RRS1-S is phosphorylated. Phosphorylation at Thr1214 in the WRKY domain maintains RRS1-R in its inactive state and also inhibits acetylation of RRS1-R by PopP2. PopP2 in turn catalyzes O-acetylation at the same site, thereby preventing its phosphorylation. Phosphorylation at other sites is required for PopP2 but not AvrRps4 responsiveness and facilitates the interaction of RRS1's C terminus with its TIR domain. Derepression of RRS1-R or RRS1-S involves effector-triggered proximity between their TIR domain and C termini. This effector-promoted interaction between these domains relieves inhibition of TIRRPS4 by TIRRRS1. Our data reveal effector-triggered and phosphorylation-regulated conformational changes within RRS1 that results in distinct modes of derepression of the complex by PopP2 and AvrRps4.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/imunologia , Arabidopsis/metabolismo , Receptores Imunológicos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sequência de Bases , Resistência à Doença/imunologia , Resistência à Doença/fisiologia , Fosforilação , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Imunidade Vegetal/fisiologia , Proteínas de Plantas , Plantas Geneticamente Modificadas , Receptores Imunológicos/genética , Tabaco/genética
15.
J Exp Bot ; 71(6): 2186-2197, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32050020

RESUMO

Plant nucleotide-binding domain, leucine-rich repeat receptor (NLR) proteins play important roles in recognition of pathogen-derived effectors. However, the mechanism by which plant NLRs activate immunity is still largely unknown. The paired Arabidopsis NLRs RRS1-R and RPS4, that confer recognition of bacterial effectors AvrRps4 and PopP2, are well studied, but how the RRS1/RPS4 complex activates early immediate downstream responses upon effector detection is still poorly understood. To study RRS1/RPS4 responses without the influence of cell surface receptor immune pathways, we generated an Arabidopsis line with inducible expression of the effector AvrRps4. Induction does not lead to hypersensitive cell death response (HR) but can induce electrolyte leakage, which often correlates with plant cell death. Activation of RRS1 and RPS4 without pathogens cannot activate mitogen-associated protein kinase cascades, but still activates up-regulation of defence genes, and therefore resistance against bacteria.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Estradiol , Proteínas NLR/genética , Doenças das Plantas , Imunidade Vegetal , Proteínas de Plantas/genética
16.
Curr Probl Cancer ; 44(2): 100476, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31078310

RESUMO

OBJECTIVE: Malignant tumors around the portal vein (PV) can cause PV stenosis, and PV stent (PVS) placement may reduce symptoms. This study aimed to investigate the efficacy and safety of PVS for symptomatic malignant PV stenosis. METHODS: Fourteen consecutive patients who underwent percutaneous transhepatic PVS placement from January 2016 to August 2018 for symptomatic malignant PV stenosis were included. Medical records were retrospectively reviewed for procedure-related complications, symptom relief, and stent patency duration after PVS. RESULTS: Of 14 patients, 7 (50%) were men (median age, 67.5 [range 32-76] years). The most common primary cancer site was the pancreas (57%). PVS placement and complete stent expansion were successful in 13 (93%) patients. PV stenosis-related symptoms were resolved in most patients, 13 of 14 (93%). There was a significant decline in median PV pressure gradient across the stenotic lesions. Postprocedural complications included 1 case (7%) each of hemothorax, intrahepatic PV thrombosis, and liver abscess. With a median follow-up of 114 (range 25-260) days, stent occlusion occurred in 5 patients (36%). The median stent patency duration was 201 days, and the overall survival was 117 days. CONCLUSIONS: PVS placement is a safe and effective method for relieving the symptom of of malignant PV stenosis.


Assuntos
Constrição Patológica/terapia , Neoplasias/complicações , Veia Porta/patologia , Stents , Adulto , Idoso , Constrição Patológica/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Oncologist ; 25(1): e186-e193, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492766

RESUMO

BACKGROUND: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). MATERIALS AND METHODS: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. RESULTS: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.


Assuntos
Pomadas/uso terapêutico , Dermatopatias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Dermatopatias/induzido quimicamente
18.
Korean J Intern Med ; 35(1): 205-214, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31795023

RESUMO

BACKGROUND/AIMS: The multidisciplinary team (MDT) approach is a cornerstone of clinical oncology. This study investigated the current state of MDT care, including patient satisfaction, in Korea. METHODS: We obtained the annual number of cancer patients who have received MDT care since 2014 from the registry of the Health Insurance Review and Assessment Service (HIRA). In addition, patients who received MDT care from August 2014 to May 2017 at four university hospitals were further characterized, and patient satisfaction was measured prospectively using a patient-reported questionnaire. RESULTS: The total number of patients who received MDT care increased from 2014 to 2016 (2,113 to 9,998 patients, respectively) in the HIRA Cohort. The type of cancer that most often required MDT was breast cancer (23.8%), followed by colorectal cancer (19.1%). In the Representative Cohort (n = 1,032), MDT was requested by the surgeon more than half the time (55.7%). The main focus of MDT was decision making for further treatment planning (99.0%). The number of doctors participating in the MDT was usually five (70.0%). After initiating an MDT approach, the treatment plan changed for 17.4% of patients. Among these patients, 359 completed a prospective satisfaction survey regarding their MDT care. The overall satisfaction with the MDT approach was very high, with an average score of 9.6 out of 10 points. CONCLUSION: The application of MDT care is a rapidly growing trend in clinical oncology, and shows high patient satisfaction. Further research is needed to determine which types of cancer patients could benefit most from MDT, and to enable MDT care to operate more efficiently so that it may expand successfully throughout Korea.


Assuntos
Neoplasias , Satisfação do Paciente , Humanos , Neoplasias/terapia , Planejamento de Assistência ao Paciente , Equipe de Assistência ao Paciente , Estudos Prospectivos , República da Coreia
19.
Opt Express ; 27(23): 34382-34391, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878486

RESUMO

Fourier ptychography uses a phase retrieval algorithm to reconstruct a high-resolution image with a wide field-of-view. Reflective-type Fourier ptychographic microscopy (FPM) is expected to be very useful for surface inspection, but the reported methods have several limitations. We propose a darkfield illuminator for reflective FPM consisting of a parabolic mirror and a flat LED panel. This increases the signal-to-noise ratio of the acquired images because the normal beam of each LED is directed toward the object. Furthermore, the LEDs do not have to be far from the object because they are collimated by the parabolic surface before illumination. Based on this, a reflective FPM with a synthesized numerical aperture (NA) of 1.06 was achieved, which is the highest value by reflective FPM as far as we know. To validate this experimentally, we measured a USAF reflective resolution target and reconstructed a high-resolution image. This resolved up to the period of 488 nm, which corresponds to the synthesized NA. Additionally, an integrated circuit was measured to demonstrate the effectiveness of surface inspection of the proposed system.

20.
Sci Rep ; 9(1): 16990, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740709

RESUMO

Although colorectal cancer is one of the most lethal cancer types in the world, its metastasis to the ovary is rare, compared to metastasis to other organs. Consequently, the genomic basis for colon-to-ovary metastasis remains unstudied, due to limited available patients, and thus there have been no attempts to construct individual-specific networks. Due to its rarity, the small sample size makes common mutations difficult to find. To overcome this problem, we herein attempted to apply a biological connectivity map called a sample-specific network (SSN), to reveal common biological functions in three samples. Our three samples were compared to a clinical dataset contained in The Cancer Genome Atlas (TCGA) Colorectal Adenocarcinoma (COAD), showing different mutational spectra, compared to matched samples based on age, gender, microsatellite instability (MSI) status, and tumor, node, metastasis (TNM) stage. The SSNs for the three samples revealed significant correlations of the mutation statuses of several apoptosis genes, in contrast to the TCGA-matched samples. Further analysis of a targeted-gene panel sequencing dataset for colon-to-ovary metastasis of primary tumor samples also confirmed significant correlations of the mutational statuses among apoptosis genes. In summary, using SSN, we successfully identified a common function (apoptosis) among our three patients having colon-to-ovary metastasis, despite no common mutations in the three patients. Such computational analyses could facilitate productive study of rare cancers and other diseases.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Mutação , Neoplasias Ovarianas/genética , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Apoptose/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Análise Mutacional de DNA/métodos , Feminino , Redes Reguladoras de Genes/genética , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Ovarianas/terapia , Transdução de Sinais/genética
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