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Aim: We aimed to determine Japanese metastatic castration resistant prostate cancer (CRPC) patients' Ra-223 treatment experience. Patients & methods: Patients answered the Cancer Therapy Satisfaction Questionnaire (CTSQ domains: Satisfaction with Therapy [SWT], Expectations of Therapy [ET], Feelings about Side Effects [FSE]), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the FACT-Bone Pain (FACT-BP) Questionnaire at baseline, during (vists 3 and 5) and after treatment (end of observation; EOO). Results: Data from 72 patients were included. Baseline median CTSQ scores SWT: 66.1 (IQR19.7), ET: 75.0 (IQR45), and FSE 68.8 (IQR 34.4) were unchanged during vists 3 and 5, but the SWT (-3.57 [IQR17.9]) and ET (-5.0 [IQR30]) decreased while FSE was unchanged (0.0 [IQR31.25]) at EOO. The median MAX-PC (18.0 [IQR 49]) score was unchanged (0.0, IQR 6) while the median FACT BP (54.0 [IQR13]) score decreased by -1.0 (IQR 8) at EOO. Conclusion: Japanese metastatic castration resistant prostate cancer patients' experience is stable during Ra-223 treatment.
What is this study about? We wanted to know the treatment experience with Radium-223 (Ra-223) among Japanese prostate cancer patients. Ra-223 is a radioactive molecule used for the treatment of metastatic castration resistant prostate cancer. We asked patients to answer different questionnaires on treatment satisfaction, anxiety and quality of life before, during, and after treatment with Ra-223. What were the results? Based on the patients' answers to our questionnaires, treatment satisfaction, anxiety and quality of life remain stable while the patients undergo treatment with Ra-223, but in some aspects may decline after treatment. What do the results mean? The results mean that patients' experience during Ra-223 treatment is stable but patients should share any concerns they have about their treatment with their doctors.
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Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/efectos adversos , Japón/epidemiología , Calidad de Vida , Neoplasias Óseas/radioterapiaRESUMEN
OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Transicionales , Quimioterapia de Mantención , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Japón , Quimioterapia de Mantención/métodos , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patologíaRESUMEN
Oxidized phospholipids have been shown to exhibit pleiotropic effects in numerous biological contexts. For example, 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxidized phospholipid formed from alkyl phosphatidylcholines, is a peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor agonist. Although it has been reported that PPARγ agonists including thiazolidinediones can induce plasma volume expansion by enhancing renal sodium and water retention, the role of azPC in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues and also investigated the effect of azPC on renal sodium handling in vivo. We showed using a microperfusion technique that azPC rapidly stimulated Na+/HCO3- cotransporter 1 (NBCe1) and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner at submicromolar concentrations in isolated PTs from rats and humans. The rapid effects (within a few minutes) suggest that azPC activates NBCe1 and NHE via nongenomic signaling. The stimulatory effects were completely blocked by specific PPARγ antagonist GW9662, ERK kinase inhibitor PD98059, and CD36 inhibitor sulfosuccinimidyl oleate. Treatment with an siRNA against PPAR gamma completely blocked the stimulation of both NBCe1 and NHE by azPC. Moreover, azPC induced ERK phosphorylation in rat and human kidney cortex tissues, which were completely suppressed by GW9662 and PD98059 treatments. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via a CD36/PPARγ/mitogen-activated protein/ERK kinase/ERK pathway. We conclude that the stimulatory effects of azPC on PT transport may be partially involved in volume expansion.
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Túbulos Renales Proximales , PPAR gamma , Fosfolípidos , Intercambiadores de Sodio-Hidrógeno , Animales , Antígenos CD36/antagonistas & inhibidores , Antígenos CD36/metabolismo , Hipoglucemiantes/farmacología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Oxidación-Reducción , PPAR gamma/metabolismo , Fosfolípidos/metabolismo , Ratas , Transducción de Señal , Intercambiadores de Sodio-Hidrógeno/metabolismo , Tiazolidinedionas/farmacologíaRESUMEN
OBJECTIVE: Radium-223 (Ra-223) dichloride is the bone-targeted radioligand therapy that prolongs overall survival (OS) in patients with bone-metastatic castration-resistant prostate cancer (CRPC). We aimed to evaluate the safety and effectiveness of this treatment in real-world practice. METHODS: We included Japanese men treated with Ra-223 for bone-metastatic CRPC from 10 institutions, retrospectively. Primary endpoint was OS. Secondary endpoint was maximum decline of alkaline phosphatase (ALP), lactate dehydrogenase, and prostate-specific antigen values, the rate of adverse events, and time to pathological fracture after Ra-223 treatment. Exploratory endpoint was the associations between clinical parameters and OS. RESULTS: In total, 73 men with bone metastatic CRPC treated with Ra-223 were enrolled. The median OS was 20.9 months. ALP levels decreased significantly from pre-treatment (p = 0.03). Anemia occurred in three (4.1%) patients. Grade ≥ 3 non-pathological fractures occurred in four (5.5%) men. Nine (12.3%) patients presented pathological fracture; 7/30 (23.3%) were in men without concomitant use of a bone-modifying agent (BMA) while 2/43 (4.7%) were in patients with concomitant BMA (p = 0.03). The median OS in patients with ≥3 cycles treatment (27.2 months, p < 0.001) or hemoglobin ≥12 g/dl (27.2 months, p = 0.001) or absence of bone pain (36.3 months, p = 0.004) was significantly longer compared to those who with ≤2 cycles or hemoglobin<12 g/dl or presence of bone paint, respectively. CONCLUSIONS: This study has shown the outcomes of Ra-223 treatment in real-world practice, where the number of treatment cycles, baseline anemia and bone pain may be useful to predict OS in Ra-223 treatment.
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Anemia , Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Masculino , Humanos , Femenino , Radio (Elemento)/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Óseas/radioterapia , Neoplasias Óseas/tratamiento farmacológico , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Dolor , Resultado del TratamientoRESUMEN
INTRODUCTION: Radium-223 (Ra-223) dichloride therapy increases overall survival and delays time to the first symptomatic skeletal event (SSE) in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Bone-modifying agents (BMA) reduce SSE in patients with bone metastasis, but there is little information on their use with Ra-223. This study aimed to investigate the effect of BMA on SSE in patients with bone metastatic CRPC treated with Ra-223 in real-world practice. METHODS: We included 73 patients treated with Ra-223 from 10 institutions in Japan. Time to the first SSE was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. We used univariate analysis to ascertain the association between variables and SSE. RESULTS: During a median follow-up of 12.7 months (interquartile range, 7-21.7), 12 (16.4%) patients presented SSE. Age and BMA use were different between men with and without SSE. The 1-year SSE-free survival rate from Ra-223 treatment initiation was 82.4% (95% CI, 69.4%-90.2%). BMA use was associated with favorable SSE-free survival (hazard risk, 0.23; 95% confidence interval, 0.061-0.85; p = 0.027). Two (4.7%) and seven (23.3%) patients presented symptomatic pathological bone fracture in groups with and without BMA use, respectively (p = 0.017). CONCLUSION: This study stresses the importance of BMA use in patients with CRPC and bone metastases in Ra-223 treatment.
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Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Masculino , Humanos , Radio (Elemento)/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radioisótopos/efectos adversos , Neoplasias Óseas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. METHODS: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). RESULTS: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. CONCLUSION: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.
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Radioterapia de Iones Pesados/efectos adversos , Neoplasias Primarias Secundarias/etiología , Neoplasias/radioterapia , Radioterapia/efectos adversos , Sarcoma/etiología , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoma/mortalidad , Adulto JovenRESUMEN
INTRODUCTION: Metastases from renal cell carcinoma develop in various organs. However, the breadth of discrepancy in response to immune checkpoint inhibitors across tumor sites within the same individual remains unclear. PATIENTS AND METHODS: We reviewed 50 patients with metastatic renal cell carcinoma who had target lesions at multiple sites and received nivolumab monotherapy (n = 36) or nivolumab plus ipilimumab (n = 14). When the best overall response in tumor burden increased at one site but decreased at other sites, the response was defined as a dissociated response. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1, and patients who met the definition of dissociated response were categorized as dissociated response. The rate of dissociated response and prognosis were evaluated. RESULTS: Eight of 36 (22%) and 4 of 14 (29%) patients treated with nivolumab and nivolumab plus ipilimumab were categorized as having dissociated response, respectively. The median overall survival of the patients treated with nivolumab was 20.2 months for those with a partial response, 6.8 months for those with stable disease, and 13.2 months for those with progressive disease, while dissociated response was not reached. There was no significant difference in the median overall survival between patients categorized as having progressive disease and those with dissociates response (P = 0.224). CONCLUSION: A certain proportion of patients with metastatic renal cell carcinoma show dissociated response when treated with immune checkpoint inhibitors. The prognosis of patients with dissociated response and progressive disease was not shown to be significantly different.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Nivolumab/uso terapéutico , Ipilimumab/uso terapéutico , Ipilimumab/efectos adversos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios RetrospectivosRESUMEN
Alopecia areata is a representative inflammatory skin disease that is associated with various environmental stimuli. While psychological stress is believed to be a major pathogenetic trigger in alopecia areata, infants and newborns also suffer from the disease, suggesting the possible presence of other environmental factors. Daily lifestyle is well known to be involved in various inflammatory diseases and influences the severity of inflammatory skin diseases. However, only a limited number of studies have summarized these influences on alopecia areata. In this review article, we summarize lifestyle factor-related influences on the pathogenesis of alopecia areata and focus on environmental factors, such as smoking, alcohol consumption, sleep, obesity, fatty acids, and gluten consumption.
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Alopecia Areata/epidemiología , Autoantígenos/metabolismo , Alopecia Areata/etiología , Alopecia Areata/inmunología , Humanos , Estilo de VidaRESUMEN
Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction sometimes exceeds tissue damage and can disrupt organ functions. Therefore, anti-inflammatory action and resolution mechanisms need to be clarified. Dietary foods are an essential daily lifestyle that influences various human physiological processes and pathological conditions. Especially, omega-3 fatty acids in the diet ameliorate chronic inflammatory skin diseases. Recent studies have identified that omega-3 fatty acid derivatives, such as the resolvin series, showed strong anti-inflammatory actions in various inflammatory diseases. Maresin-1 is a derivative of one of the representative omega-3 fatty acids, i.e., docosahexaenoic acid (DHA), and has shown beneficial action in inflammatory disease models. In this review, we summarize the detailed actions of maresin-1 in immune cells and inflammatory diseases.
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Ácidos Docosahexaenoicos/farmacología , Inflamación/dietoterapia , Antiinflamatorios/farmacología , Dieta , Ácidos Docosahexaenoicos/análogos & derivados , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos Omega-3/farmacología , HumanosRESUMEN
Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.
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Dieta , Estilo de Vida , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversos , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma de Células de Merkel/etiología , Carcinoma de Células Escamosas/etiología , Ritmo Circadiano , Fibras de la Dieta/farmacología , Frutas , Humanos , Melanoma/etiología , Obesidad/complicaciones , Factores de Riesgo , Fumar/efectos adversos , Verduras , Melanoma Cutáneo MalignoRESUMEN
Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid's function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.
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Angioedema/tratamiento farmacológico , Angioedema/fisiopatología , Ácidos Grasos/uso terapéutico , Angioedema/metabolismo , Bradiquinina/metabolismo , Permeabilidad Capilar , Ácidos Grasos/metabolismo , Ácidos Grasos/fisiología , Histamina/metabolismo , Humanos , Prostaglandinas/metabolismo , Prostaglandinas/fisiologíaRESUMEN
In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.
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Biomarcadores/análisis , Erupciones por Medicamentos/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico , Animales , Diagnóstico Diferencial , Erupciones por Medicamentos/genética , Erupciones por Medicamentos/metabolismo , Humanos , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/metabolismoRESUMEN
IgA, previously called Henoch-Schönlein vasculitis, is an essential immune component that drives the host immune response to the external environment. As IgA has the unique characteristic of a flexible response to broad types of microorganisms, it sometimes causes an autoreactive response in the host human body. IgA vasculitis and related organ dysfunction are representative IgA-mediated autoimmune diseases; bacterial and viral infections often trigger IgA vasculitis. Recent drug developments and the presence of COVID-19 have revealed that these agents can also trigger IgA vasculitis. These findings provide a novel understanding of the pathogenesis of IgA vasculitis. In this review, we focus on the characteristics of IgA and symptoms of IgA vasculitis and other organ dysfunction. We also mention the therapeutic approach, biomarkers, novel triggers for IgA vasculitis, and epigenetic modifications in patients with IgA vasculitis.
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Biomarcadores/análisis , Epigénesis Genética , Inmunoglobulina A/metabolismo , Vasculitis/terapia , Animales , Humanos , Vasculitis/diagnóstico , Vasculitis/etiología , Vasculitis/metabolismoRESUMEN
After Evans and colleagues identified the lipomatous tumor with a well-differentiated liposarcoma in a subcutaneous location or within a muscle layer, namely, atypical lipomatous tumor (ALT), this malignancy has been investigated to clarify the characteristics of clinical behavior and genomic changes. As one of the important issues for clinicians, it is a hot topic of how to distinguish ALT from benign lipoma in the clinical aspect. Recent studies revealed novel findings to clarify the risk factor for the diagnosis of ALT and molecular targets for the treatment of ALT. Clinical characteristics of superficial-type ALT well reflect the subcutaneous location of the tumor and are slightly different compared to deep-type ALT, such as tumor size. In addition, there has been a recent discovery of novel findings in ALT-related genes, namely, HMG2A (high mobility group protein 2a), YEATS4 (YEATS domain containing 4), and CPM (Carboxypeptidase M). Recent updates on treatment for advanced ALT are well developed including immunotherapy and conducting clinical trials. Finally, this review introduces one of the hot topics of ALT research focused on epigenetic changes: their attention in recent updates on clinical characteristics and the novel discovery of related genes, treatment, and epigenetic modifications in atypical lipomatous tumors.
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Liposarcoma/genética , Animales , Antineoplásicos/uso terapéutico , Epigénesis Genética , Predisposición Genética a la Enfermedad , Humanos , Liposarcoma/diagnóstico por imagen , Liposarcoma/tratamiento farmacológico , Liposarcoma/patologíaRESUMEN
Melanoma is a severe and life-threatening malignancy derived from melanocytes. The traditional treatment for melanoma could not sustain satisfactory outcomes long term; however, the recent immune checkpoint treatment has made a breakthrough in these problems. Nivolumab is a representative immune checkpoint treatment, and this PD-1-targeted therapy has evolutionally developed and improved the clinical outcome in a recent decade. On the other hand, the clinical application of immune checkpoint treatment presents clinicians with novel questions, especially how to obtain additional efficacy and overcome the disadvantage by using this treatment. To answer these problems, we first investigated the distribution of PD-L1 in various organs to clarify the organs most affected by anti-PD-1 antibody treatment. Among various organs, lung, placenta, spleen, heart, and thyroid highly expressed PD-L1, while skin, thalamus, hippocampus, ovary, stomach, testis, and prostate showed lower expressions of PD-L1. Furthermore, the immune profiles were also examined in tumors and peripheral blood in patients with melanoma. PD-1 was highly expressed in CD8 and CD4 cells, and B cells also highly expressed PD-1 compared with NK cells. However, there was no significant difference in Th1/Th2/Th17 cytokines and inhibitory cytokine IL-10. Although nevus showed a low expression of PD-L1 compared with healthy skin, PD-L1 expression was increased in growth-phase melanoma. Finally, we analyzed the peripheral blood profiles in patients treated with nivolumab. PD-1-bearing dendritic cells (DCs) were increased during nivolumab treatment and Lin-CD11c+HLA-DR+ cells were highly increased during nivolumab treatment. These findings indicate a clue to answering the problems during nivolumab treatment and suggest to us the importance of multiple aspect observation during immune checkpoint treatment.
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Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Melanoma/sangre , Melanoma/inmunología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/inmunología , Antígeno B7-H1/metabolismo , Citocinas/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Melanoma/terapia , Nivolumab/farmacología , Nivolumab/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/terapiaRESUMEN
Throughout life, it is necessary to adapt to the Earth's environment in order to survive. A typical example of this is that the daily Earth cycle is different from the circadian rhythm in human beings; however, the ability to adapt to the Earth cycle has contributed to the development of human evolution. In addition, humans can consume and digest Earth-derived foods and use luxury materials for nutrition and enrichment of their lives, as an adaptation to the Earth's environment. Recent studies have shown that daily lifestyles are closely related to human health; however, less attention has been paid to the fact that obesity due to excessive energy intake, smoking, and alcohol consumption contributes to the development of inflammatory skin diseases. Gluten or wheat protein, smoking and alcohol, sleep disturbance, and obesity drive the helper T (Th)1/Th2/Th17 immune response, whereas dietary fiber and omega-3 fatty acids negatively regulate inflammatory cytokine production. In this review, we have focused on daily lifestyles and the mechanisms involved in the pathogenesis of inflammatory skin diseases.
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Dermatitis/fisiopatología , Estilo de Vida , Enfermedades de la Piel/fisiopatología , HumanosRESUMEN
The skin is the outermost layer of the body and is exposed to many environmental stimuli, which cause various inflammatory immune responses in the skin. Among them, fungi are common microorganisms that colonize the skin and cause cutaneous fungal diseases such as candidiasis and dermatophytosis. The skin exerts inflammatory responses to eliminate these fungi through the cooperation of skin-component immune cells. IL-17 producing cells are representative immune cells that play a vital role in anti-fungal action in the skin by producing antimicrobial peptides and facilitating neutrophil infiltration. However, the actual impact of IL-17-producing cells in cutaneous fungal infections remains unclear. In this review, we focused on the role of IL-17-producing cells in a series of cutaneous fungal infections, the characteristics of skin infectious fungi, and the recognition of cell components that drive cutaneous immune cells.
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Candidiasis/inmunología , Hongos/inmunología , Interleucina-17/inmunología , Piel/inmunología , Células Th17/inmunología , Tiña/inmunología , Animales , Candidiasis/microbiología , Hongos/fisiología , Humanos , Interleucina-17/metabolismo , Infiltración Neutrófila/inmunología , Proteínas Citotóxicas Formadoras de Poros/inmunología , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piel/microbiología , Células Th17/metabolismo , Tiña/microbiologíaRESUMEN
Insulin is known to promote sodium transport and regulate gluconeogenesis in renal proximal tubules. Although protein kinase B (also known as Akt) and mammalian target of rapamycin complexes (mTORC) have been established as key regulators in the insulin signaling pathway, their roles in proximal tubules are poorly understood. To help define this, we examined the components of insulin signaling in sodium transport and gluconeogenesis in isolated human and rat proximal tubules, and also investigated the role of insulin in sodium handling and mTORC1 in insulin signaling in vivo. In isolated human and rat proximal tubules, Akt and mTORC1/2 inhibition suppressed insulin-stimulated sodium-bicarbonate co-transporter 1 (NBCe1) activity, whereas mTORC1 inhibition had no effect. Akt2 and mTORC2 gene silencing largely inhibited insulin-stimulated NBCe1 activity, whereas silencing of Akt1 and mTORC1 had no effect. Furthermore, insulin decreased sodium excretion, and this effect depended on phosphoinositide 3 kinase in vivo. Moreover, insulin reduced glucose production in rat proximal tubules and the expression of gluconeogenic genes in human and rat proximal tubules. Akt and mTORC1 inhibition largely abolished the observed insulin-mediated inhibitory effects. Gene silencing of insulin receptor substrate 1 (IRS1), Akt2, mTORC1, and mTORC2 also abolished insulin-mediated inhibition of gluconeogenesis. Additionally, in vivo, mTORC1 inhibition abolished insulin-mediated inhibitory effects in rat proximal tubules, although not in liver. These results indicate that insulin-stimulated proximal tubule sodium transport is mediated via the Akt2/mTORC2 pathway, whereas insulin-suppressed proximal tubule gluconeogenesis is mediated via the IRS1/Akt2/mTORC1/2 pathway. Thus, distinct pathways may play important roles in hypertension and hyperglycemia in metabolic syndrome and diabetes.
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Gluconeogénesis , Insulina , Animales , Humanos , Insulina/metabolismo , Túbulos Renales Proximales/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Sodio/metabolismoRESUMEN
This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.
Asunto(s)
L-Lactato Deshidrogenasa/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/enzimología , Neoplasias de la Próstata Resistentes a la Castración/mortalidadRESUMEN
BACKGROUND: ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223. METHODS: Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint. RESULTS: Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6-not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7-NE) (HR = 0.907, 95% CI 0.501-1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively. CONCLUSIONS: In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: NCT02043678.