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1.
Exp Cell Res ; 424(1): 113503, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36731710

RESUMO

Most lung adenocarcinoma-associated EGFR tyrosine kinase mutations are either an exon 19 deletion (19Del) or L858R point mutation in exon 21. Although patients whose tumors contain either of these mutations exhibit increased sensitivity to tyrosine kinase inhibitors, progression-free and overall survival appear to be longer in patients with 19Del than in those with L858R. In mutant-transfected Ba/F3 cells, 19Del and L858R were compared by multi-omics analyses including proteomics, transcriptomics, and metabolomics. Proteome analysis identified increased plastin-2, TKT, PDIA5, and ENO1 expression in L858R cells, and increased EEF1G expression in 19Del cells. RNA sequencing showed significant differences between 19Del and L858R cells in 112 genes. Metabolome analysis showed that amino acids, adenylate, guanylate, NADPH, lactic acid, pyruvic acid glucose 6-phosphate, and ribose 5-phosphate were significantly different between the two mutant cells. Because GSH was increased with L858R, we combined osimertinib with the GSH inhibitor buthionine sulfoximine in L858R cells and observed synergistic effects. The complexity of EGFR 19Del and L858R mutant cells was demonstrated by proteomics, transcriptomics, and metabolomics analyses. Therapeutic strategies for lung cancer with different EGFR mutations could be considered because of their different metabolic phenotypes.


Assuntos
Neoplasias Pulmonares , Proteômica , Humanos , Transcriptoma , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Éxons , Inibidores de Proteínas Quinases/farmacologia
2.
J Obstet Gynaecol Res ; 49(5): 1429-1434, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36787726

RESUMO

PURPOSE: This study established the prognostic significance of the uroflowmetry flow curve shape in the presence of voiding dysfunction following transvaginal mesh surgery. METHODS: This is a retrospective study of 439 symptomatic cystocele patients who underwent anterior wall repair with transvaginal mesh surgery. Uroflowmetry and postvoid residual were used to evaluate voiding function both preoperatively and 12 months postoperatively. The patients were divided into two groups: those with and without postoperative voiding dysfunction, and the predictors of postoperative voiding dysfunction were analyzed. The shape of the urine flow curve was analyzed for its influence on the presence of postoperative voiding dysfunction. RESULTS: Thirty-five participants were in the voiding dysfunction group, while 404 were in the nonvoiding dysfunction group. Multivariate analysis was conducted by adding an interrupted-shaped curve to age, Qmax, and postvoid residual, which showed significant differences in univariate analysis, found that age 68 years or older (odds ratio [OR]: 7.68, 95%CI 1.02-58, p = 0.048), postvoid residual ≥110 mL (OR: 2.8, 95%CI 1.25-6.29, p = 0.013) and interrupted-shaped curve (OR: 2.47, 95%CI 1.07-5.69, p = 0.034) were discovered to be independent risk factors for the presence of voiding dysfunction after transvaginal mesh surgery. CONCLUSIONS: Following transvaginal mesh surgery for cystocele, three variables were found to be predictive of voiding dysfunction: the old age, excessive postvoid residual, and an interrupted-shaped flow curve. The uroflowmetry flow curve shape has the potential to be a new predictor of postoperative voiding dysfunction.


Assuntos
Cistocele , Prolapso de Órgão Pélvico , Transtornos Urinários , Feminino , Humanos , Idoso , Prolapso de Órgão Pélvico/cirurgia , Cistocele/complicações , Cistocele/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Transtornos Urinários/etiologia
3.
IJU Case Rep ; 5(5): 389-392, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36090932

RESUMO

Introduction: This report aims to describe our experience in the pelvic floor reconstruction of anterior enterocele following radical cystectomy by transvaginal surgery using a mesh for abdominal wall hernia repair. Case presentation: An 84-years-old woman developed pelvic organ prolapse 4 months after undergoing robot-assisted radical cystectomy. After examination, she was diagnosed with a midline anterior enterocele. Considering the thinness of the vaginal wall and the large defect of the vaginal wall muscle layer, we performed transvaginal repair using a mesh for abdominal wall hernia repair designed to reduce the adhesion to the intestinal tract. Conclusion: At the 1-year follow-up, neither recurrence nor complications were observed. This showed that transvaginal mesh surgery for abdominal wall hernia repair could be a treatment option for pelvic organ prolapse with a vaginal wall muscle layer defect after radical cystectomy.

4.
J Obstet Gynaecol Res ; 48(9): 2466-2473, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35735289

RESUMO

AIM: In this study, we retrospectively analyzed the medium-term efficacy and safety of surgery with transobturator two-arm transvaginal mesh for cystocele and to verify whether the anterior arms are necessary for Japanese-style transvaginal mesh surgery. METHODS: The study included 203 patients with cystocele who underwent transobturator two-arm transvaginal mesh at our hospital between August 2015 and June 2017 and received appropriate follow-up care for at least 48 months after surgery. RESULTS: The Pelvic Organ Prolapse Quantification stage was III in all the patients. Intraoperative complications included two cases of bladder injury and one case of more than 200 mL of blood loss. The mean observation period was 51.9 months, and prolapse recurred in the operated compartment in nine patients (4.4%). No cases of mesh exposure were observed. In comparing the preoperative characteristics of the 9 patients with prolapse recurrence at the surgical site with those of the other 194 patients, we found that the recurrence rate was significantly higher among patients in whom point Ba being 3.5 cm or more and among patients younger than 66 years. CONCLUSIONS: Transobturator two-arm transvaginal mesh for cystocele was as good and safe as the procedure previously reported with four-arm mesh; thus, it was possible to omit the anterior mesh arms in Japanese-style transvaginal mesh surgery. Patients should be informed preoperatively that prolapse recurs at a significantly higher rate among younger patients and in those whose point Ba being 3.5 cm or more.


Assuntos
Cistocele , Prolapso de Órgão Pélvico , Cistocele/cirurgia , Humanos , Japão , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento
5.
Int J Urol ; 29(5): 435-440, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35108757

RESUMO

OBJECTIVES: The aim of this study was to verify the safety and efficacy of transvaginal mesh by analyzing the 2-year follow-up data of patients performed by a surgeon with a high volume of procedures. METHODS: A total of 617 patients with pelvic organ prolapse underwent transvaginal mesh by a single surgeon. Complications and anatomical status of each patient were examined up to 24 months after surgery. Risk factors for the recurrence were also analyzed. RESULTS: Regarding complications, we experienced 10 patients (3.8%) of bladder injuries in anterior transvaginal mesh and eight (3.4%) in anterior and posterior transvaginal mesh. Massive blood loss was observed in four patients, but there was no case of blood transfusion. Mesh exposures were seen in seven patients (1.2%). A total of 100 patients (16.2%) had prolapse recurrence, defined as the Pelvic Organ Prolapse Quantification System stage ≥II. As to recurrences on the operated compartments, we observed five patients (2.0%) for anterior transvaginal mesh, three (6.5%) for posterior transvaginal mesh, five (7.4%) for combined transvaginal mesh, and 31 (14.2%) in anterior and posterior transvaginal mesh. Regarding Point C before operation in the anterior and posterior transvaginal mesh, the recurrence rates were more than 23% in patients with a Point C of 4 or more. Binominal regression analyses showed that higher body mass index, younger age, and higher stage of uterine prolapse were significant risk factors. CONCLUSIONS: The transvaginal mesh surgery is safe when conducted by experts. However, the recurrence rate may exceed 20% for high-stage uterine prolapse even when conducted by experts.


Assuntos
Prolapso de Órgão Pélvico , Cirurgiões , Prolapso Uterino , Índice de Massa Corporal , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos
6.
Exp Cell Res ; 409(2): 112940, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34808132

RESUMO

Lung cancer that exhibits epidermal growth factor receptor (EGFR) gene mutation is sensitive to EGFR-tyrosine kinase inhibitors (TKIs), such as osimertinib. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) may be involved in overcoming EGFR-TKI resistance. Growth inhibition, colony formation, apoptosis, and mRNA/protein levels in four osimertinib-sensitive and resistant cell lines transfected with small interfering RNA (siRNA) targeting ROR1 (siROR1) were evaluated. Cell growth and colony formation were suppressed and apoptosis was increased in all cell lines treated with siROR1. Although EGFR, AKT, and ERK phosphorylation were not suppressed in all cell lines, TGF-ß2, AXL, CDH2, PARP1, PEG10, and TYMS mRNA expression levels were reduced. The combination of osimertinib with siROR1 was effective for the four cell lines, particularly in the two osimertinib-sensitive lines. In conclusion, targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer may be a novel therapeutic option.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Resistencia a Medicamentos Antineoplásicos , Mutação , RNA Interferente Pequeno/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Apoptose , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Terapia Combinada , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Urol ; 28(5): 474-492, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33650242

RESUMO

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post-micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery.


Assuntos
Sintomas do Trato Urinário Inferior , Prolapso de Órgão Pélvico , Bexiga Urinária Hiperativa , Feminino , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Qualidade de Vida , Urodinâmica
8.
Int J Urol ; 27(11): 996-1000, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776359

RESUMO

OBJECTIVES: To investigate techniques of transvaginal mesh prolapse surgery in Japan, and compare complication rates by surgeons' specialty and experience with transvaginal mesh prolapse surgery. METHODS: We carried out an anonymous questionnaire survey for surgeons attending a national transvaginal mesh prolapse surgery meeting in 2010. The surgeons were asked to state their specialty, practice patterns, transvaginal mesh prolapse surgery techniques and the number of transvaginal mesh prolapse procedures carried out as an operator including the complications that occurred. RESULTS: A total of 118 surgeons (59% of the attendees) responded to the questionnaire. The mean age was 44.0 ± 9.1 years, 54 (46%) were gynecologists and 64 (54%) were urologists. All urologists and 78% of gynecologists carried out anti-incontinence surgery (midurethral sling), whereas more gynecologists (93%) carried out native tissue repair than urologists (73%). Most of both specialties (each 98%) avoided prophylactic anti-incontinence surgery during prolapse surgery. Concomitant hysterectomy during transvaginal mesh prolapse surgery was generally avoided. Surgeons reached a consensus regarding the critical transvaginal mesh prolapse surgery techniques: hydrodissection (98%) and the full-thickness dissection (the "Lychee layer"; 69%). A total of 11 935 Prolift-type transvaginal mesh prolapse procedures were carried out and the following complications were reported: bladder injury (1.6%), rectal injury (0.3%), ureteral injury (0.1%), blood transfusion (0.2%), vaginal exposure (2.8%) and recurrence requiring reoperation (1.1%). Although complications did not differ between specialty, bladder injury, transfusion and vaginal exposure were less prevalent with experienced surgeons (≥50 transvaginal mesh prolapse surgery cases). CONCLUSIONS: Over 10 000 transvaginal mesh prolapse surgery had been carried out in Japan with a relatively low complication rate until 2010. This survey shows that surgeons' experience could lead to a decrease in the amount of transvaginal mesh prolapse surgery complications.


Assuntos
Prolapso de Órgão Pélvico , Slings Suburetrais , Cirurgiões , Adulto , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/cirurgia , Slings Suburetrais/efeitos adversos , Telas Cirúrgicas/efeitos adversos
9.
Lung Cancer ; 139: 170-178, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809978

RESUMO

OBJECTIVE: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in a subset of malignant cells. However, it remains unknown whether ROR1 is targetable in malignant mesothelioma (MM). Therefore, in this study, we investigated the effects of ROR1 inhibition in mesothelioma cells. MATERIALS AND METHODS: Growth inhibition, colony formation, apoptosis, and mRNA/protein levels using siRNA-transfected MM cells were evaluated. Cluster analysis using Gene Expression Omnibus repository of transcriptomic information was also performed. RESULTS: Our results indicated that in three (H2052, H2452, and MESO-1) among four MM cell lines, ROR1 inhibition had anti-proliferative and apoptotic effects and suppressed the activation of AKT and STAT3. Although growth inhibition by siROR1 was minimal in another mesothelioma cell line (H28), colony formation was significantly suppressed. Microarray, quantitative polymerase chain reaction, and Western blot analyses showed that there were differences in the suppression of mRNA and proteins between H2452 and H28 cells transfected with siROR1 compared with those transfected with control siRNA. Cluster analysis further showed that MM tumors had relatively high ROR1 expression, although the cluster in them was different from that in MM cell lines. Thymidylate synthase, a target of pemetrexed, was downregulated in H2452 cells transfected with siROR1. Accordingly, a combination of pemetrexed with siROR1 was found to be effective in the three MM cell lines we studied. CONCLUSION: Our findings may provide novel therapeutic insight into the treatment of advanced MM.


Assuntos
Apoptose , Mesotelioma Maligno/patologia , Pemetrexede/farmacologia , Neoplasias Pleurais/patologia , RNA Interferente Pequeno/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores , Antineoplásicos/farmacologia , Proliferação de Células , Terapia Combinada , Humanos , Mesotelioma Maligno/genética , Mesotelioma Maligno/terapia , Neoplasias Pleurais/genética , Neoplasias Pleurais/terapia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Transdução de Sinais , Células Tumorais Cultivadas
10.
J Infect Chemother ; 25(7): 567-570, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005565

RESUMO

We performed a questionnaire-based, retrospective, nationwide survey on perioperative management and antimicrobial prophylaxis for mid-urethral sling surgery for stress urinary incontinence in Japan to realize the clinical practice and risk factors for SSI. Records of women receiving transobturator tape (TOT) and tension-free vaginal tape (TVT) surgeries from 2010 to 2012 were obtained from hospitals belonging to the Japanese Society of Pelvic Organ Prolapse Surgery. The questionnaire addressed hospital volume, perioperative management, and SSI. Risk factors for SSI were investigated by comparing cases with and without SSI. The data from 97 hospitals and a total 1627 TOT and 1045 TVT surgeries were analyzed. Mean case volumes of TOT and TVT surgeries were 7.3 ± 14.9 and 7.1 ± 17.8 cases per year, respectively. Preoperative hair removal, bowel preparation, and urine culture were routinely performed at 44 (45.3%), 31 (32.0%), and 22 (22.7%) hospitals, respectively. First-generation (51.5%) or second-generation (34.0%) cephalosporin was mostly used for antimicrobial prophylaxis. SSI was reported only in 6 patients (0.22%) and none of them developed abscesses. None of the factors we could evaluate from the questionnaire were found to be significantly associated with SSI. SSI after mid-urethral slings rarely occurred in Japan (0.22%) and no parameters about perioperative managements significantly increased SSI. However, further studies with more detail information of each patient and operation are required to confirm their appropriate perioperative managements for mid-urethral slings.


Assuntos
Assistência Perioperatória/estatística & dados numéricos , Slings Suburetrais/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/estatística & dados numéricos , Monitoramento Epidemiológico , Feminino , Hospitais/estatística & dados numéricos , Humanos , Japão/epidemiologia , Assistência Perioperatória/métodos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Inquéritos e Questionários/estatística & dados numéricos , Procedimentos Cirúrgicos Urológicos/instrumentação
11.
BMC Womens Health ; 18(1): 174, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359244

RESUMO

BACKGROUND: We evaluated the effect of transvaginal mesh (TVM) surgery for voiding function and continence using noninvasive examination and questionnaire. The present study aimed to ascertain which categories of patients need concomitant mid-urethral sling (MUS) after TVM surgery. METHODS: We included women who underwent TVM procedure between November 2009 and October 2013. Data from noninstrumented uroflowmetry and questionnaires about urinary symptoms were analyzed. RESULTS: The present study investigated the cases of 961 women who underwent TVM surgery. The persistence of stress urinary incontinence (SUI) was 57.6%. Almost all the parameters measured using uroflowmetry and questionnaires significantly improved in all types of urinary incontinence 12 months after surgery. A history of hysterectomy, preoperative high flow (corrected maximum flow rate > 1.5), and preoperative urge urinary incontinence were independent risk factors for the persistence of SUI. CONCLUSIONS: TVM for pelvic organ prolapse improved subjective and objective voiding function. Mixed urinary incontinence (MUI) patients with high urinary flow may be suitable for concomitant MUS with TVM because of the high level of SUI persistence.


Assuntos
Telas Cirúrgicas/efeitos adversos , Bexiga Urinária/fisiopatologia , Incontinência Urinária por Estresse/etiologia , Vagina/cirurgia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/etiologia , Slings Suburetrais/efeitos adversos , Inquéritos e Questionários , Incontinência Urinária/etiologia , Urodinâmica/fisiologia
12.
Ther Clin Risk Manag ; 14: 1457-1465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30174428

RESUMO

PURPOSE: Cure-oriented treatment of malignant lymphoma (ML) is possible even in an advanced stage; however, the progression of drug-induced interstitial lung disease (DILD) sometimes accounts for poor clinical outcomes. This study aims to assess the incidence and clinical characteristics of DILD among patients with ML and compares the serum level of Krebs von den Lungen-6 (KL-6) with that of circulating thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17) as a diagnostic biomarker for DILD. PATIENTS AND METHODS: Between July 2011 and August 2016, we enrolled 36 patients with ML who were undergoing systemic chemotherapy at our hospital. Then, we evaluated the serum concentration of KL-6 and TARC/CCL17 by a sandwich-type electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: DILD developed in 22.2% of patients with ML. All patients recovered immediately after the discontinuation of causative drug and/or glucocorticoid therapy. Although the sensitivity of both TARC/CCL17 and KL-6 was almost equal, the mean concentration of serum KL-6 after the progression of interstitial lung disease was significantly higher than that before progression. CONCLUSION: DILD developed in patients who were treated with first-line rituximab combined regimen. Remarkably, TARC/CCL17 and KL-6 seemed approximately equal as a predictive biomarkers for DILD; however, KL-6 was more specific than TARC/CCL17.

13.
Neurourol Urodyn ; 37(3): 1074-1081, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29527737

RESUMO

AIMS: We conducted a nationwide survey on perioperative management and antimicrobial prophylaxis of transvaginal mesh surgeries for pelvic organ prolapse in Japan to understand the practice and risk factors for surgical site infection (SSI). METHODS: Health records of women undergoing tension-free vaginal mesh (TVM) surgeries from 2010 to 2012 were obtained from 135 medical centers belonging to the Japanese Society of Pelvic Organ Prolapse Surgery. The questionnaire addressed hospital volume, perioperative management, and SSI. Risk factors for SSI were investigated by comparing cases with and without SSI. RESULTS: The hospital volume among institutions varied from 0 to 248 per year (median 16.7). Preoperative hair removal, bowel preparation, and urine culture were routinely performed at 74 (55%), 66 (49%), and 24 (18%) hospitals, respectively. Prophylactic antimicrobials used were mostly first-generation (43%) or second-generation (42%) cephalosporin. SSI was reported in 86 of 9323 patients (0.92%). A multivariate analysis indicated lower hospital volume (odds ratio [OR], 0.995 [by 1-point increase]; P < 0.001), preoperative bowel preparation (OR, 2.08; P = 0.013), non-routine urine culture (OR, 3.00; P = 0.0006), and the use of antibiotics other than first-generation cephalosporin (OR, 5.29; P = 0.0011) as significant risk factors for SSI. In contrast, the cut-off points of hospital volume for preventing SSI was 116.7 cases (area under curve: 0.61). CONCLUSION: The prevalence of SSI in TVM surgeries was 0.92% in Japan. Lower hospital volume, bowel preparation, non-routine preoperative urine culture, and prophylactic antibiotics other than first-generation cephalosporin significantly elevated the incidence of SSI.


Assuntos
Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Japão , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia
14.
Exp Cell Res ; 344(2): 194-200, 2016 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-27180268

RESUMO

The combination effect of pacritinib, a novel JAK2/FLT3 inhibitor, with erlotinib, the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on non-small cell lung cancer cells with EGFR activating mutations was investigated. The combination showed synergistic effects on JAK2-mediated EGFR TKI-resistant PC-9/ER3 cells in some cases. The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or control in PC-9/ER3 cells. Receptor tyrosine kinase array profiling demonstrated that pacritinib suppressed MET in the PC-9/ER3 cells. The combined treatment of pacritinib and erlotinib in PC-9/ER3 xenografts showed more tumor shrinkage compared with each drug as monotherapy. Western blotting revealed that pMET in tumor samples was inhibited. These results suggest MET suppression by pacritinib may play a role in overcoming the EGFR-TKI resistance mediated by JAK2 in the PC-9/ER3 cells. In conclusion, pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Janus Quinase 2/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Mutação/genética , Pirimidinas/uso terapêutico , Animais , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Carcinoma Pulmonar de Células não Pequenas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Cloridrato de Erlotinib/farmacologia , Feminino , Humanos , Camundongos SCID , Fosforilação/efeitos dos fármacos , Pirimidinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Low Urin Tract Symptoms ; 8(1): 5-29, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26789539

RESUMO

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.


Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/terapia , Algoritmos , Feminino , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Qualidade de Vida , Inquéritos e Questionários
16.
Ther Clin Risk Manag ; 11: 949-59, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26124663

RESUMO

INTRODUCTION: Serum Krebs von den Lungen-6 (KL-6) level is an established diagnostic marker of interstitial lung disease (ILD). However, it is also elevated in patients with non-small cell lung cancer (NSCLC). The significance of circulating thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17) in malignant diseases remains unknown. METHODS: We measured circulating TARC/CCL17 and KL-6 using enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively, in 26 patients with malignant disease and six patients with benign lung disease (BLD). The cutoff levels were 500 U/mL for KL-6 and 450 pg/mL for TARC/CCL17. The significance of the markers was evaluated in relationship to the presence of ILD (n=10). The statistical significance was set at P<0.05. RESULTS: The KL-6 positive ratio was significantly higher in the patients with NSCLC (n=17) than in those with BLD. There was a significant difference in the KL-6 positive ratio between the patients with NSCLC without ILD and those with BLD without ILD. However, there were no significant differences in the TARC/CCL17 positive ratio between the patients with NSCLC and BLD or between those with NSCLC without ILD and those with BLD without ILD. The TARC/CCL17 positive ratio was significantly higher in the patients with malignancy and ILD than in those without ILD. There was also a significant difference in the TARC/CCL17 positive ratio between the patients with NSCLC without ILD and those with ILD. CONCLUSION: TARC/CCL17 may be useful for the diagnosis of ILD in patients with malignancies. Confirmation of the results is warranted through a large-scale study.

17.
Am J Cancer Res ; 5(4): 1553-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26101718

RESUMO

INTRODUCTION: Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) play a major role in suppressing the immune system during the formation of the PD-1/PD-L1 pathway, which transmits an inhibitory signal to reduce T cell activity. PD-L1 is often expressed in various malignant tumors. In contrast, PD-1 is generally observed in activated lymphocytes and myeloid-derived dendritic cells. Of the malignant cells, only Jurkat cells under special conditions and angioimmunoblastic T-cell lymphoma tissue cells express PD-1 on their surface. METHODS: To clarify whether the PD-1/PD-L1 pathway participates in the immunotolerance of small-cell lung cancer (SCLC) cells, we examined the expressions of PD-1 and PD-L1 on the cell surface of SCLC cell lines using flow cytometry and reverse transcription polymerase chain reaction. RESULTS: Among the four SCLC cell lines examined, only SBC-3 expressed both PD-1 and PD-L1. CONCLUSIONS: We demonstrated that both PD-1 and PD-L1 molecules were co-expressed on the surface of SCLC cells. Although the biological implications of this remain unclear, we speculate that PD-1 and its ligand on the SCLC cells may participate in the growth inhibition of tumor cells as reported in cytotoxic T cells.

18.
Nihon Hinyokika Gakkai Zasshi ; 103(4): 617-22, 2012 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-23120996

RESUMO

OBJECTIVES: Female urological diseases, including pelvic organ prolapse and urinary incontinence, are common in elderly people, but public knowledge about these diseases is limited. We analyzed information tools that patients with female urological disease utilized to acquire information about their diseases. MATERIALS AND METHODS: This study included 3,480 patients who presented to our female urological clinic between January 2005 and December 2008. We conducted a questionnaire survey on what information tools were used for information gathering. RESULTS: The newspaper was the leading information tool (39.9%), followed by referral from another clinic (17.8%), internet (15.7%), TV (14.8%), recommendation by family or friends (5.5%), books or magazines (3.2%), and informative sessions for the public (0.6%). The temporal trend in the rate of information tool use over the 4 years showed that internet use increased significantly every year (p trend = 0.041) and was the most utilized tool in 2008, along with referral from other clinics. The rate of newspaper or TV use depended on their volumes of the female urological diseases. Additionally, no change over the study period was observed for the rate of internet utilization for patients in their 40s or under; however, it increased in patients in their 50s or over, and patients in their 50s and 60s utilized the internet as often as patients in their 40s or under in 2008. CONCLUSIONS: The newspaper was the most utilized information tool for patients with female urological diseases. However, internet use for gathering disease information is increasing, and the internet may be the most important information tool in the near future.


Assuntos
Serviços de Informação , Doenças Urológicas , Idoso , Feminino , Humanos , Internet , Pessoa de Meia-Idade , Jornais como Assunto , Pacientes Ambulatoriais
19.
J Obstet Gynaecol Res ; 38(5): 867-70, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22448605

RESUMO

The tension-free vaginal mesh (TVM) procedure has become one of the commonly used treatments for pelvic organ prolapse (POP) due to good clinical outcome. However, there are several technical difficulties associated with this procedure. We performed fluoroscopy for imaging of the surgical procedure on the TVM to resolve the technical problems regarding needle penetration. Fluoroscopic imaging with rectogram and cystogram demonstrated the positions of the needle, pelvic organs and index finger for needle guidance in the TVM procedure. Fluoroscopic imaging may be useful to understand the movement of surgical devices in the blind space, objectively evaluate the surgeon's skill, avoid injury to the pelvic organs, and detect any such injury immediately should it occur.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/métodos , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas , Vagina/cirurgia , Idoso , Feminino , Fluoroscopia , Humanos , Agulhas , Prolapso de Órgão Pélvico/diagnóstico por imagem , Resultado do Tratamento , Vagina/diagnóstico por imagem
20.
Int J Urol ; 18(8): 555-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21711397

RESUMO

A variety of tension-free vaginal mesh (TVM) systems are available for surgical treatment of pelvic organ prolapse (POP). These include Prolift, Apogee/Perigee and Avaulta, all of which vary in terms of mesh size, shape and surgical technique to such an extent that they cannot truly be considered the same operation for the purpose of evaluating results. I began carrying out self-made mesh cut out from Gynemesh PS in 2005. This system has four main characteristics: (i) the mesh is intended as a replacement for defective visceral pelvic fascia; (ii) it bridges between the left and right arcus tendineus fascia pelvis (white line, or ATFP); (iii) large-size mesh is held in place by passing cannulas through the obturator fascia (anterior wall) or the sacrospinous ligament (SSL) to attach the arms of the mesh graft; and (iv) the bladder neck is preserved. The mesh that I have used since then has been essentially similar to the Prolift System, developed by a French TVM group, in terms of size and shape of its central portion. Mesh grafts used for the anterior wall are quite large, so skillful execution will provide sufficient room between the left and right ATFP in almost all cases. This video discusses the fundamental techniques necessary for skillful execution of the tension-free vaginal mesh (TVM) procedure using the Prolift System, focusing on the following points: (i) surgical separation of the correct layers of the vaginal wall, and the area separated, and effective hemostasis; (ii) precise puncture technique, especially the second puncture for the anterior TVM (TVM-A) procedure and the sacrospinous ligament (SSL) puncture in the posterior TVM (TVM-P) procedure; (iii) firmly securing the mesh to the vaginal wall or cervical canal; and (iv) careful mesh placement and formation of a bridge between the left and right arcus tendineus fascia pelvis (ATFP). Proper separation of the vaginal wall layers, in particular, is crucial for preventing unnecessary blood loss and mesh erosion. The second puncture in the TVM-A is the most important of the puncture maneuvers for the procedure. Penetrating the tough tissue near the ischial spine represents a significant challenge, and the SSL penetration in the TVM-P procedure is unexpectedly difficult for those without sufficient experience. In order to become proficient, the surgeon must have hands-on experience under the supervision of experts. Finally, TVM is a relatively new procedure, so one must master the fundamentals before gaining true proficiency. The technique does not call for virtuosity on the part of the surgeon, but key points must be mastered to reduce the risk of complications and recurrences. With repeated hands-on training, surgical skills will gradually improve to the requisite level. This is a translated section of a video article originally published in Japanese as a DVD in the Audio-Visual Journal Vol.15 No.15. 2009 by The Japanese Urological Association.


Assuntos
Prolapso de Órgão Pélvico/cirurgia , Slings Suburetrais , Telas Cirúrgicas , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Procedimentos Cirúrgicos Urológicos/métodos
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