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1.
Am J Physiol Renal Physiol ; 324(4): F353-F361, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36656987

RESUMO

This study aimed to clarify whether downregulation of K+-Cl- cotransporter 2 (KCC2) in the sacral parasympathetic nucleus (SPN) of the lumbosacral spinal cord, from which the efferent pathway innervating the bladder originates, causes cellular hyperexcitability and triggers detrusor overactivity (DO) in spinal cord injury (SCI). SCI was produced by Th8-9 spinal cord transection in female C57BL/6 mice. At 4 wk after SCI, CLP290, a KCC2 activator, was administered, and cystometry was performed. Thereafter, neuronal activity with c-fos staining and KCC2 expression in cholinergic preganglionic parasympathetic neurons in the SPN was examined using immunohistochemistry. Firing properties of neurons in the SPN region were evaluated by extracellular recordings in the spinal cord slice preparations. DO evident as nonvoiding contractions was significantly reduced by CLP290 treatment in SCI mice. The number of c-fos-positive cells and coexpression of c-fos in choline acetyltransferase-positive cells were decreased in the SPN region of the SCI CLP290-treated group versus the SCI vehicle-treated group. KCC2 immunoreactivity was present on the cell membrane of SPN neurons and normalized fluorescence intensity of KCC2 in choline acetyltransferase-positive SPN neurons was decreased in the SCI vehicle-treated group versus the spinal intact vehicle-treated group but recovered in the SCI CLP290-treated group. Extracellular recordings showed that CLP290 suppressed the high-frequency firing activity of SPN neurons in SCI mice. These results indicated that SCI-induced DO is associated with downregulation of KCC2 in preganglionic parasympathetic neurons and that activation of KCC2 transporters can reduce DO, increase KCC2 expression in preganglionic parasympathetic neurons, and decrease neuronal firing of SPN neurons in SCI mice.NEW & NOTEWORTHY This study is the first report to suggest that activation of the Cl- transporter K+-Cl- cotransporter 2 may be a therapeutic modality for the treatment of spinal cord injury-induced detrusor overactivity by targeting bladder efferent pathways.


Assuntos
Traumatismos da Medula Espinal , Simportadores , Camundongos , Feminino , Animais , Cloretos/metabolismo , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/farmacologia , Colina O-Acetiltransferase/uso terapêutico , Camundongos Endogâmicos C57BL , Traumatismos da Medula Espinal/complicações , Medula Espinal/metabolismo
2.
Int J Urol ; 30(1): 57-61, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513615

RESUMO

OBJECTIVES: To assess the postoperative status of clinically localized prostate cancer patients who underwent robot-assisted radical prostatectomy (RARP) with a focus on de novo overactive bladder (OAB). METHODS: The present study included 156 patients who did not have preoperative OAB and underwent RARP between December 2015 and April 2020 at our institution. Patients were divided into the de novo OAB group and non-OAB group based on the findings of overactive bladder symptoms score (OABSS) 6 months after RARP, and comparative assessments were performed between the two groups. RESULTS: Six months after RARP, de novo OAB was detected in 38 (24.4%) out of 156 patients. Body mass index (BMI) and the proportion of patients with hypertension were significantly higher in the de novo OAB group than in the non-OAB group. No significant differences were observed in the other characteristics examined. Furthermore, the preoperative findings of uroflowmetry and a urodynamic study did not significantly differ between the two groups. Despite the lack of significant differences in preoperative OABSS, total international prostate symptom score, the voiding symptom score, storage symptom score, and quality of life score between the two groups, all of these findings 6 months after RARP were significantly worse in the de novo OAB group than in the non-OAB group. Among the several factors examined, only BMI was independently associated with the development of de novo OAB 6 months after RARP. CONCLUSIONS: Patients with a high BMI may develop de novo OAB after RARP, resulting in the significant deterioration of lower urinary tract symptoms.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Bexiga Urinária Hiperativa , Masculino , Humanos , Bexiga Urinária Hiperativa/epidemiologia , Bexiga Urinária Hiperativa/etiologia , Próstata/cirurgia , Qualidade de Vida , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos
3.
Int J Urol ; 30(9): 730-736, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36575640

RESUMO

OBJECTIVES: The present study comprehensively investigated the significance of several factors reflecting the therapeutic effects of anticancer treatment on overall survival (OS) in advanced urothelial cancer (UC) patients receiving sequential systemic therapy. METHODS: This study included 101 consecutive advanced UC patients who received first-line platinum-based combination chemotherapy followed by second-line pembrolizumab. The impacts of the following factors on OS in these patients were analyzed: responses to chemotherapy, responses to pembrolizumab, progression-free survival (PFS) with chemotherapy, PFS with pembrolizumab, and second PFS (PFS2). RESULTS: The median age of patients was 71 years, and 35 and 66 had UC in the upper urinary tract and bladder, respectively. objective response rate to first-line chemotherapy and second-line pembrolizumab were 37.6% and 19.8%, respectively. Median PFS with chemotherapy, pembrolizumab, and PFS2 were 5, 4, and 9 months, respectively. Uni- and multivariate analyses of the five factors examined identified PFS with pembrolizumab and PFS2 as independent surrogates for OS, with PFS2 (hazard ratio [HR] = 0.23) being more closely associated with OS than PFS with pembrolizumab (HR = 0.31). Furthermore, uni- and multivariate analyses of various prognostic parameters showed the independent impacts of baseline performance status (PS) and neutrophil-to-lymphocyte ratio (NLR) on PFS2. CONCLUSIONS: The present results suggest the potential of PFS2 as an optimal surrogate for OS in advanced UC patients receiving standard sequential systemic therapy and indicate that intensive treatment needs to be considered for those with poor PS and/or high NLR prior to the introduction of first-line chemotherapy.


Assuntos
Carcinoma de Células de Transição , Platina , Humanos , Idoso , Intervalo Livre de Progressão , Platina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico
4.
Eur J Clin Microbiol Infect Dis ; 41(11): 1315-1325, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36156177

RESUMO

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.


Assuntos
Candidemia , Candidíase , Anfotericina B , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candida glabrata , Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Farmacorresistência Fúngica , Fluconazol , Hospitais Universitários , Humanos , Japão/epidemiologia , Estudos Longitudinais , Micafungina , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Voriconazol
5.
Jpn J Clin Oncol ; 52(8): 944-949, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35462401

RESUMO

BACKGROUND: The objective of the present study was to evaluate the prognostic impact of the upper urinary tract cancer status on recurrence-free survival and progression-free survival, and to develop risk stratification systems that include the upper urinary tract cancer status for patients with non-muscle invasive bladder cancer. PATIENTS AND METHODS: The present study included 40 (upper urinary tract cancer-non-muscle invasive bladder cancer group) and 285 (non-muscle invasive bladder cancer alone group) patients with and without a history of prior or concomitant upper urinary tract cancer, respectively. Nine clinicopathological findings between the two groups were compared, and risk stratification systems for the recurrence and progression of non-muscle invasive bladder cancer were developed. RESULTS: Recurrence-free survival and progression-free survival in the upper urinary tract cancer-non-muscle invasive bladder cancer group were significantly inferior to those in the NMIBC alone group (P < 0.001 and P = 0.006, respectively). Multivariate analyses identified the following independent prognosticators: multiplicity and upper urinary tract cancer status for recurrence-free survival, and pT category and upper urinary tract cancer status for progression-free survival. Significant differences were noted by the risk stratification systems based on the positive number of independent predictors of recurrence-free survival and progression-free survival (P < 0.001 and P = 0.007, respectively). The concordance indices of recurrence-free survival were 0.627, 0.588 and 0.499 in this study stratification, EORTC risk table and CUETO model, respectively. Those of progression-free survival were 0.752, 0.740 and 0.714, respectively. CONCLUSION: The present results suggest the significant impact of a history of prior or concomitant UUTC on recurrence-free survival and progression-free survival in non-muscle invasive bladder cancer patients, and risk stratification systems that include the upper urinary tract cancer status for the recurrence and progression of non-muscle invasive bladder cancer are promising tools for predicting the outcomes of these patients.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Progressão da Doença , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia
6.
Int J Clin Oncol ; 26(9): 1745-1751, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34255227

RESUMO

BACKGROUND: Cabazitaxel has played an important role in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC); however, several types of sequential therapy against mCRPC have been performed in routine clinical practice. The objective of this study was to investigate the impact of third-line treatment on prognostic outcomes of mCRPC patients. METHODS: This study retrospectively analyzed the clinical outcomes of 166 patients who received 3 agents following the diagnosis of mCRPC, consisting of 81 sequentially treated with either abiraterone or enzalutamide and then docetaxel, followed by third-line cabazitaxel (group A) and 85 treated with 3 agents, including abiraterone, enzalutamide, and docetaxel (group B). RESULTS: There were no significant differences in major characteristics at the introduction of the third-line agent between these 2 groups. The proportion of patients with prostate-specific antigen (PSA) reduction > 50% by cabazitaxel in group A was significantly greater than that by either third-line agent in group B. Both PSA progression-free survival (PFS) and overall survival (OS) following third-line therapy in group A were significantly longer than those in group B. Furthermore, OS after the diagnosis of mCRPC in group A was significantly longer than that in group B. Multivariate analysis identified independent predictors of favorable prognostic outcomes after third-line therapy as follows: high-performance status (PS), low PSA level and third-line cabazitaxel for PSA PFS, and high PS, low lactate dehydrogenase level and third-line cabazitaxel for OS. CONCLUSIONS: The introduction of cabazitaxel as a third-line agent could markedly improve the prognostic outcomes of mCRPC patients.

7.
Jpn J Clin Oncol ; 50(6): 718-721, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32322885

RESUMO

OBJECTIVES: Second transurethral resection is recommended for patients diagnosed with high-risk non-muscle invasive bladder cancer; however, there have been several studies showing conflicting findings regarding the advantage of second transurethral resection. The objective of this study was to investigate the prognostic significance of second transurethral resection using propensity score matched analysis. PATIENTS AND METHODS: This study retrospectively included 164 consecutive patients who underwent initial transurethral resection and were diagnosed with high-risk non-muscle invasive bladder cancer. Of these, 56 subsequently received second transurethral resection, and the remaining 108 underwent initial transurethral resection alone. RESULTS: After adjusting patient variables by propensity score matching, 44 patients were included in each group. There was no significant difference in recurrence-free, progression-free or overall survival between these two groups. CONCLUSIONS: These findings suggested no significant impact of second transurethral resection on the prognosis of high-risk non-muscle invasive bladder cancer patients; therefore, it may be necessary to perform a reassessment focusing on the indication for second transurethral resection by conducting a large-scale prospective study.


Assuntos
Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos , Idoso , Feminino , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Pontuação de Propensão , Estudos Retrospectivos
8.
Int J Clin Oncol ; 24(3): 256-261, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30328531

RESUMO

BACKGROUND: The association between UGT1A1 polymorphism and etoposide-induced toxicities is still not clear. The aim of this study was to assess the association between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and severe hematologic toxicities in Japanese patients receiving etoposide plus platinum chemotherapy for small-cell lung cancer. METHODS: This retrospective analysis included patients with small-cell lung cancer who had received their first-line chemotherapy with etoposide plus cisplatin or carboplatin, between October 2008 and April 2018, at the University of Fukui Hospital. The relationship between UGT1A1 polymorphisms and first-cycle neutropenia as well as thrombocytopenia was evaluated. RESULTS: A total of 55 patients were enrolled. The incidence of grade 4 neutropenia during the first cycle of etoposide-based chemotherapy was higher in patients with homozygous (hmz) polymorphisms for UGT1A1*28 and *6 (*28/*28, *6/*6, and *6/*28) than in patients with wild-type (wt) (*1/*1) and heterozygous (htz) (*1/*28 and *1/*6) polymorphisms (88% vs 43% P = 0.03). The incidence of febrile neutropenia and grade 4 thrombocytopenia, however, was not significantly different. Multivariate analysis suggested that grade 4 neutropenia associated significantly with an hmz UGT1A1 genotype [odds ratio (OR) 11.3; P = 0.04] and administration of granulocyte colony-stimulating factor (G-CSF) before the neutrophil counts dropped to < 500 cells/µL (OR; P = 0.01). CONCLUSIONS: UGT1A1*28 and UGT1A1*6 mutations might be regarded as predictors for etoposide-induced grade 4 neutropenia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Glucuronosiltransferase/genética , Neoplasias Pulmonares/tratamento farmacológico , Neutropenia/induzido quimicamente , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Povo Asiático/genética , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Neoplasias Pulmonares/genética , Masculino , Neutropenia/genética , Polimorfismo Genético , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/genética , Trombocitopenia/induzido quimicamente , Trombocitopenia/genética
9.
J Neurochem ; 131(6): 755-66, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25175638

RESUMO

Intraplantar injection of 0.4% formalin into the rat hind paw leads to a biphasic nociceptive response; an 'acute' phase (0-15 min) and 'tonic' phase (16-120 min), which is accompanied by significant phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the contralateral striatum at 120 min post-formalin injection. To uncover a possible relationship between the slow-onset substance P (SP) release and increased ERK1/2 phosphorylation in the striatum, continuous infusion of SP into the striatum by reverse microdialysis (0.4 µg/mL in microdialysis fiber, 1 µL/min) was performed to mimic volume neurotransmission of SP. Continuous infusion for 3 h of SP reduced the duration of 'tonic' phase nociception, and this SP effect was mediated by neurokinin 1 (NK1) receptors since pre-treatment with NK1 receptor antagonist CP96345 (10 µM) blocked the effect of SP infusion. However, formalin-induced 'tonic' phase nociception was significantly prolonged following acute injection of the MAP/ERK kinase 1/2 inhibitor PD0325901 (100 pmol) by microinjection. The coinfusion of SP and PD0325901 significantly increased the 'tonic' phase of nociception. These data demonstrate that volume transmission of striatal SP triggered by peripheral nociceptive stimulation does not lead to pain facilitation but a significant decrease of tonic nociception by the activation of the SP-NK1 receptor-ERK1/2 system. Noxious stimulation induces a slow-onset substance P (SP) release as a volume transmitter, activating extra-synaptic NK1 receptors, and evokes phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The SP-NK1-ERK1/2 system in the striatum decreases tonic nociception.


Assuntos
Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Substância P/farmacologia , Animais , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Medição da Dor , Fosforilação/efeitos dos fármacos , Ratos Wistar , Receptores da Neurocinina-1/metabolismo , Medula Espinal/efeitos dos fármacos , Substância P/administração & dosagem , Substância P/metabolismo , Transmissão Sináptica/fisiologia
10.
Zootaxa ; 3755: 1-32, 2014 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-24869807

RESUMO

The Japanese species of subgenus Conoblasta Förster 1869 sensu Aubert (1978) and Kuslitzky (1974, 2007) of the genus Glypta Gravenhorst 1829 are reviewed. No reliable synapomorphies are found for the species of Conoblasta after all and thus we conclude that they should be treated as a tentative species group. Eighteen species of the Conoblasta species group, including 11 new species (G. cognata sp. nov., G. daisetsuzana sp. nov., G. densepunctata sp. nov., G. flavitarsus sp. nov., G. ichitai sp. nov., G. karasawensis sp. nov., G. nipponica sp. nov., G. shigaensis sp. nov., G. suwai sp. nov., G. touyaensis sp. nov., G. zenibakoensis sp. nov.) and two newly recorded species (G. chinensis (Uchida 1956) and G. extincta Ratzeberg 1852), are recognized from Japan. A key to the Japanese species is provided.


Assuntos
Himenópteros/anatomia & histologia , Himenópteros/classificação , Animais , Demografia , Feminino , Himenópteros/fisiologia , Japão , Masculino , Especificidade da Espécie
11.
Zootaxa ; 3784: 501-27, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24872069

RESUMO

Japanese species of the genus Apophua Morley, 1913, are revised. Eleven species are found from Japan and two of them, A. elegans sp. nov. and A. yamato sp. nov., are newly described. Distribution data and an updated key to Japanese species are provided.


Assuntos
Himenópteros/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Animais , Ecossistema , Feminino , Himenópteros/anatomia & histologia , Japão , Masculino
12.
Anticancer Res ; 44(4): 1417-1423, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537988

RESUMO

BACKGROUND/AIM: The therapeutic impact of combination treatment with an immune checkpoint inhibitor (ICI) and chemotherapeutic agent on patients with urothelial cancer (UC) remains controversial. Therefore, the present study investigated differences in the therapeutic effects of combination therapy with cisplatin plus anti-mouse programmed death (PD)-1 antibody according to the dose of cisplatin using the mouse bladder tumor model MBT2. MATERIALS AND METHODS: The effects of treatment with two different doses cisplatin and/or anti-mouse PD-1 antibody on tumor growth after the subcutaneous injection of MBT2 cells were compared. Infiltrating patterns of lymphocytes into tumors after treatment were assessed using immunohistochemical staining. RESULTS: MBT2 tumor volumes were significantly larger in mice receiving high-dose cisplatin alone than in those receiving low-dose cisplatin alone. Combination treatment with cisplatin plus anti-mouse PD-1 antibody exerted significantly stronger growth inhibitory effects on MBT2 tumors than treatment with either agent alone, irrespective of cisplatin doses; however, no significant differences were observed in MBT2 tumor volumes between mice receiving anti-mouse PD-1 antibody plus high-dose cisplatin and those receiving anti-mouse PD-1 antibody plus low-dose cisplatin. Furthermore, CD8+ to CD3+ and CD8+ to CD11b+ T-lymphocyte ratios in MBT2 tumors were both significantly higher in the low-dose cisplatin alone group than in the high-dose cisplatin alone group, whereas no significant differences were noted in either ratio between the two different combination treatment regimens. CONCLUSION: When combined with ICI, a lower dose of cisplatin may achieve favorable antitumor effects in UC patients by preventing lymphocyte exhaustion.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , Cisplatino , Receptor de Morte Celular Programada 1 , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Linfócitos T/patologia
13.
Anticancer Res ; 44(2): 781-786, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307571

RESUMO

BACKGROUND/AIM: Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC. PATIENTS AND METHODS: The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis. RESULTS: The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049). CONCLUSION: These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Hipertensão , Neoplasias Renais , Piridinas , Humanos , Carcinoma de Células Renais/patologia , Intervalo Livre de Progressão , Antineoplásicos/efeitos adversos , Neoplasias Renais/patologia , Estudos Retrospectivos , Anilidas/efeitos adversos , Hipertensão/tratamento farmacológico
14.
In Vivo ; 38(4): 1859-1864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936944

RESUMO

BACKGROUND/AIM: Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice. PATIENTS AND METHODS: Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated. RESULTS: The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death. CONCLUSION: The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.


Assuntos
Doxorrubicina , Neoplasias Retroperitoneais , Sarcoma , Humanos , Feminino , Masculino , Idoso , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Pessoa de Meia-Idade , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Sarcoma/mortalidade , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/secundário , Neoplasias Retroperitoneais/patologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Metástase Neoplásica , Adulto , Estudos Retrospectivos , Estadiamento de Neoplasias
15.
Biol Pharm Bull ; 36(5): 719-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23649332

RESUMO

In Japan, pharmacists who are in consultation with doctors independently prepare medications in an attempt to meet the needs of patients in the hospital. In particular, the need for hospital preparations to treat cancer is high and diverse. However, unlike gov]ernment-approved medications, independently and individually prepared hospital preparations raise concerns about their effectiveness, safety, economic efficiency, quality control, etc. One way to address these concerns is to commercialize these preparations and to understand the difference between necessity and demand from various points of view. We have conducted nation-wide utilization surveys and evaluated the literature on hospital preparations. On the basis of the findings of this survey, we have concluded that pharmaceutical companies and the government need to implement the commercialization of hospital preparations in clinical practice. In this report, we discuss the significance of commercialization of hospital preparations, concerns regarding pharmaceutical preparations, and our recent efforts on cancer treatment. We hope to continuously contribute to society and to medical care by improving individualized care and by commercializing medications needed in clinical practice.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Serviço de Farmácia Hospitalar , Coleta de Dados , Composição de Medicamentos , Humanos
16.
Int J Clin Oncol ; 18(1): 96-104, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22095245

RESUMO

BACKGROUND: Ethnic differences in drug susceptibility and toxicity are a major concern, not only in drug development but also in the clinical setting. We review the toxicity profiles of docetaxel according to dose and ethnicity. METHODS: We analyzed phase II and III clinical trials that included a once-every-3-weeks single-agent docetaxel arm. Logistic regression analysis was applied to identify the significant variables affecting the reported incidence of docetaxel-induced severe neutropenia. RESULTS: Multivariate logistic regression analysis identified studies conducted in Asia [odds ratio (OR) 19.0; 95% confidence interval (95% CI) 3.64-99.0] and docetaxel dose (OR 1.08; 95% CI 1.03-1.13) as independent variables for the incidence of grade 3/4 neutropenia. CONCLUSIONS: There is a significant difference in the incidence of docetaxel-induced severe neutropenia between Asian and non-Asian clinical studies. Physicians and pharmacists should consider ethnic diversity in docetaxel toxicity when interpreting the results of clinical trials.


Assuntos
Neoplasias/complicações , Neoplasias/epidemiologia , Neutropenia/patologia , Taxoides/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Docetaxel , Relação Dose-Resposta a Droga , Etnicidade/genética , Humanos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Taxoides/administração & dosagem , Taxoides/farmacocinética
17.
Zootaxa ; 3736: 187-97, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25112622

RESUMO

In the context of the biodiversity conservation of the oceanic Ogasawara Islands, the parasitoid species of Aulacidae are reviewed. We examined material from eight islands with or without invasion of the introduced lizard Anolis carolinensis (Voigt 1832) (green anoles): two species of Pristaulacus Kieffer 1900, P. boninensis Konishi, 1989, and P. anijimensis sp. nov., are recognized. The former species is widely distributed in the islands, whereas the latter species is found from a single island only, Anijima Island. Although this island appears to be currently well preserved, the recent introduction of green anoles will probably affect the conservation status of many species, including the endemic P. anijimensis sp. nov. A description of the new species, detailed drawings and descriptions of genitalia of both recognized species, an updated key to Japanese Aulacidae, and a brief discussion on the conservation aspects of Aulacidae in the Ogasawara Islands are provided.


Assuntos
Biodiversidade , Himenópteros/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Animais , Ecossistema , Feminino , Himenópteros/anatomia & histologia , Ilhas , Japão , Masculino
18.
Zootaxa ; 5352(4): 594-600, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38221426

RESUMO

A new species, Priopoda macrophyae sp. nov., is described. This species is an important parasitoid of a serious pest of Japanese ash (Fraxinus japonica), Macrophya satoi Shinohara & Li, 2015. This species resembles P. otaruensis (Uchida, 1930) in the black colouration of the hind coxa, hind femur, and all metasomal tergites, but can be clearly distinguished by the length of the malar space, the smooth interspace of the punctures on the mesopleuron, the large smooth area of the speculum, the complete and strongly raised propodeal carinae, and the length of the first metasomal tergite. The bionomics of this species is also noted. The host record of this species is also the first record for Asian species of this genus.


Assuntos
Besouros , Fraxinus , Himenópteros , Oleaceae , Animais , Japão
19.
Zootaxa ; 5339(5): 401-426, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38221407

RESUMO

The Japanese species of the genus Leptobatopsis Ashmead, 1900 are revised. A total of eight species are recorded from Japan, including a new species, Leptobatopsis yaima sp. nov., and three species, L. annularis Kasparyan, 2007, L. koreana Lee & Kang, 2015, and L. nigricapitis Chandra & Gupta, 1977, newly recorded from Japan. A Chinese species L. annularis Sheng & Sun, 2013 is a homonym of L. annularis Kasparyan, 2007. Both species are clearly different, and we therefore propose a new replacement name for the former, L. sinica (nom. nov.). Leptobatopsis daedeokensis Lee & Kang, 2015 is newly synonymised with L. annularis Kasparyan, 2007. The taxonomic position of L. nigra immaculata Momoi, 1971 is changed from a subspecies of L. nigra Cushman, 1933 to separate species, L. immaculata. The female of L. badia Momoi, 1970 is newly described. A key to the Japanese species of this genus is proposed.


Assuntos
Himenópteros , Feminino , Animais , Japão
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