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1.
Biochem Biophys Res Commun ; 733: 150701, 2024 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-39326256

RESUMO

The sensitivity of currently available screening tools for urothelial carcinoma (UC) remains unsatisfactory particularly at early stages. Hence, we aimed to establish a novel blood-based screening tool for urothelial carcinoma. We measured serum d-amino acid levels in 108 and 192 patients with and without UC individuals in the derivation cohort, and 15 and 25 patients with and without UC in the validation cohort. Serum d-asparagine levels were significantly higher in patients with UC than in those without UC (p < 0.0001). We developed a novel screening equation for the diagnosis of urothelial carcinoma using d-asparagine in serum and estimated the glomerular filtration rate (eGFR). Serum d-asparagine levels adjusted for eGFR exhibited high performance in the diagnosis of UC (AUC-ROC, 0.869; sensitivity, 80.6 %; specificity, 82.7 %), even in early-stage UC (AUC-ROC: 0.859, sensitivity: 83.3 %, specificity: 82.3 %), which were previously misdiagnosed via urinary occult blood or urine cytology. This established strategy combined with urinary occult blood, improves diagnostic ability (sensitivity: 93.7 %, specificity: 70.1 %).


Assuntos
Asparagina , Taxa de Filtração Glomerular , Humanos , Masculino , Feminino , Asparagina/sangue , Pessoa de Meia-Idade , Idoso , Detecção Precoce de Câncer/métodos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Sensibilidade e Especificidade , Neoplasias Urológicas/sangue , Neoplasias Urológicas/diagnóstico , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Urotélio/patologia , Urotélio/metabolismo , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina
2.
BJU Int ; 134(2): 207-218, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38344879

RESUMO

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Japão/epidemiologia
3.
Jpn J Clin Oncol ; 54(3): 346-351, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38146119

RESUMO

BACKGROUND: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. METHODS: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy. RESULTS: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure. CONCLUSIONS: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.


Assuntos
Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Idoso , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Androgênios , Antígeno Prostático Específico
4.
Int J Clin Oncol ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39379757

RESUMO

BACKGROUND: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear. METHODS: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves. RESULTS: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck. CONCLUSIONS: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully.

5.
Int J Urol ; 30(1): 20-27, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36168966

RESUMO

OBJECTIVES: Cabazitaxel is a next-generation taxane that can prolong overall survival after docetaxel treatment in patients with metastatic castration-resistant prostate cancer. However, the efficacy of cabazitaxel varies among these patients. The clinical indicators of the prognosis after cabazitaxel treatment were analyzed. METHODS: A retrospective review of patients who received cabazitaxel between February 2015 and June 2021 was performed. All patients had metastatic castration-resistant prostate cancer. Prognostic factors for prostate-specific antigen progression-free and overall survival were analyzed by Cox proportional-hazards analysis and the log-rank test. RESULTS: The study comprised 57 patients who received cabazitaxel (median 4 cycles, range 1-27) at a starting dose of 15-25 mg/m2 . The median age and follow-up duration were 70 years and 9.2 months. The median prostate-specific antigen progression-free survival and overall survival were 2.6 and 10.5 months, respectively. Univariate analysis showed that previous androgen receptor-axis-targeted therapy before cabazitaxel treatment was the only significant risk factor (hazard ratio 2.784, p = 0.022) for prostate-specific antigen progression-free survival. Multivariate analysis for overall survival revealed that poor performance status (≥1) (hazard ratio 2.107, p = 0.039), low hemoglobin (hazard ratio 0.142, p = 0.010), and high neutrophil-lymphocyte ratio (hazard ratio 9.150, p = 0.032) at baseline were significantly associated with a poor prognosis. CONCLUSIONS: Previous androgen receptor-axis-targeted therapy was the only risk factor for biochemical progression. Poor performance status, anemia, and high neutrophil-lymphocyte ratio were risk factors for poor prognosis in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel. These risk factors seem useful for identifying patients with survival benefit from cabazitaxel treatment.


Assuntos
Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos , Resultado do Tratamento , Japão/epidemiologia , Intervalo Livre de Doença , Taxoides/uso terapêutico
6.
Hinyokika Kiyo ; 69(4): 107-112, 2023 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-37183041

RESUMO

A 55-year-old female presented to the hospital with a complaint of gross hematuria. Transurethral resection of bladder tumor was performed. The specimens pathologically showed signet ring cells and no urothelial carcinoma components. Magnetic resonance imaging and computed tomographic (CT) scan revealed bladder tumor, cervical metastasis, bilateral ovarian metastasis, and multiple lymph node metastasis. She was diagnosed with a primary signet ring cell carcinoma of the urinary bladder with cT3bN2M1, and was treated with chemotherapy of gemcitabine and cisplatin combination (GC). After 2 cycles of GC, the value of CEA which was elevated to 106 ng/ml before treatment, became negative. CT scan showed that her disease had successfully responded to the chemotherapy, and remained efficacious till the end of 6 cycles. The patient subsequently received 1 cycle of gemcitabine and nedaplatin and 3 cycles of avelumab due to renal insufficiency. Yet, 14 months after diagnosis, cerebellar metastases appeared and the patient died of meningeal carcinomatosis.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias da Bexiga Urinária , Feminino , Humanos , Pessoa de Meia-Idade , Cisplatino , Gencitabina , Bexiga Urinária , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Carcinoma de Células em Anel de Sinete/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Int J Cancer ; 151(4): 623-636, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35403732

RESUMO

Western high-fat diets (HFD) are regarded as a major risk factor for prostate cancer (PCa). Using prostate-specific Pten-knockout mice as a PCa model, we previously reported that HFD promoted inflammatory PCa growth. The composition of the gut microbiota changes under the influence of diet exert various effects on the host through immunological mechanisms. Herein, we investigated the etiology of HFD-induced inflammatory cancer growth and the involvement of the gut microbiome. The expression of Hdc, the gene responsible for histamine biosynthesis, and histamine levels were upregulated in large prostate tumors of HFD-fed mice, and the number of mast cells increased around the tumor foci. Administration of fexofenadine, a histamine H1 receptor antagonist, suppressed tumor growth in HFD-fed mice by reducing the number of myeloid-derived suppressor cells and suppressing IL6/STAT3 signaling. HFD intake induced gut dysbiosis, resulting in the elevation of serum lipopolysaccharide (LPS) levels. Intraperitoneal injection of LPS increased Hdc expression in PCa. Inhibition of LPS/Toll-like receptor 4 signaling suppressed HFD-induced tumor growth. The number of mast cells increased around the cancer foci in total prostatectomy specimens of severely obese patients. In conclusion, HFD promotes PCa growth through histamine signaling via mast cells. Dietary high-fat induced gut dysbiosis might be involved in the inflammatory cancer growth.


Assuntos
Dieta Hiperlipídica , Neoplasias da Próstata , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta , Disbiose , Histamina , Humanos , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias da Próstata/etiologia
8.
BMC Cancer ; 22(1): 1292, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494792

RESUMO

BACKGROUND: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. METHODS: Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. EXPECTED OUTCOME: Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. TRIAL REGISTRATION: The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.


Assuntos
Neoplasias , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Reparo de DNA por Recombinação , Poli(ADP-Ribose) Polimerases/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Mutação
9.
J Neurosci ; 40(7): 1560-1570, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31924610

RESUMO

Both visual and proprioceptive information contribute to the accuracy of limb movement, but the mechanism of integration of these different modality signals for movement control and learning remains controversial. We aimed to elucidate the mechanism of multisensory integration for motor adaptation by evaluating single-trial adaptation (i.e., aftereffect) induced by visual and proprioceptive perturbations while male and female human participants performed reaching movements. The force-channel method was used to precisely impose several combinations of visual and proprioceptive perturbations (i.e., error), including an instance when the directions of perturbation in both stimuli opposed each another. In the subsequent probe force-channel trial, the lateral force against the channel was quantified as the aftereffect to clarify the mechanism by which the motor adaptation system corrects movement in the event of visual and proprioceptive errors. We observed that the aftereffects had complex dependence on the visual and proprioceptive errors. Although this pattern could not be explained by previously proposed computational models based on the reliability of sensory information, we found that it could be reasonably explained by a mechanism known as divisive normalization, which was the reported mechanism underlying the integration of multisensory signals in neurons. Furthermore, we discovered evidence that the motor memory for each sensory modality developed separately in accordance with a divisive normalization mechanism and that the outputs of both memories were integrated. These results provide a novel view of the utilization and integration of different sensory modality signals in motor adaptation.SIGNIFICANCE STATEMENT The mechanism of utilization of multimodal sensory information by the motor control system to perform limb movements with accuracy is a fundamental question. However, the mechanism of integration of these different sensory modalities for movement control and learning remains highly debatable. Herein, we demonstrate that multisensory integration in the motor learning system can be reasonably explained by divisive normalization, a canonical computation, ubiquitously observed in the brain (Carandini and Heeger, 2011). Moreover, we provide evidence of a novel idea that integration does not occur at the sensory information processing level, but at the motor execution level, after the motor memory for each sensory modality is separately created.


Assuntos
Memória/fisiologia , Modelos Biológicos , Atividade Motora/fisiologia , Propriocepção/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Força da Mão , Humanos , Análise dos Mínimos Quadrados , Masculino , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Estresse Mecânico , Adulto Jovem
10.
Int J Mol Sci ; 21(17)2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32842545

RESUMO

Bladder cancer is the most common cancer of the urinary tract. Although nonmuscle-invasive bladder cancers have a good prognosis, muscle-invasive bladder cancers promote metastases and have a poor prognosis. Comprehensive analyses using RNA sequence of clinical tumor samples in bladder cancer have been reported. These reports implicated the candidate genes and pathways that play important roles in carcinogenesis and/or progression of bladder cancer. Further investigations for the function of each mutation are warranted. There is suggestive evidence for several environmental factors as risk factors of bladder cancer. Environmental factors such as cigarette smoking, exposure to chemicals and gases, bladder inflammation due to microbial and parasitic infections, diet, and nutrition could induce several genetic mutations and alter the tumor microenvironment, such as immune cells and fibroblasts. The detailed mechanism of how these environmental factors induce carcinogenesis and/or progression of bladder cancer remains unclear. To identify the relationship between the mutations and the lifestyle could be useful for prevention and treatment of bladder cancer.


Assuntos
Exposição Ambiental/efeitos adversos , Mutação , Neoplasias da Bexiga Urinária/etiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Cistite/complicações , Dieta , Humanos , Estilo de Vida , Síndrome Metabólica/complicações , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Fatores de Risco , Fumar/efeitos adversos , Telomerase/genética , Neoplasias da Bexiga Urinária/genética
11.
Cancer Sci ; 110(2): 617-628, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30536551

RESUMO

Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty-three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell-free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics-based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50-166 bp) to large (167-250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log-rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer-specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC.


Assuntos
Carcinoma de Células Renais/genética , DNA Tumoral Circulante/genética , DNA de Neoplasias/genética , Neoplasias Renais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Fragmentação do DNA , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética
12.
Cancer Sci ; 108(12): 2495-2502, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28985012

RESUMO

There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly upregulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by receiver operating characteristic curve analysis (sensitivity, 70.0%; specificity, 64.0%; area under the curve = 0.722; multiple logistic regression analysis: odds ratio, 1.07; 95% confidence interval, 1.03-1.11; P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in PBMCs than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in PBMCs from healthy volunteers was significantly elevated following coculture with RCC cells compared to those cocultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , beta-Tromboglobulina/biossíntese , Adulto , Idoso , Área Sob a Curva , Carcinoma de Células Renais/sangue , Feminino , Humanos , Neoplasias Renais/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , beta-Tromboglobulina/análise
13.
Prostate ; 77(14): 1383-1388, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28845570

RESUMO

BACKGROUND: Tumor-infiltrating macrophages, which are thought to be derived from blood monocytes, interact with tumor cells to promote cancer progression. The aim of this study was to assess the association of peripheral blood monocyte count with pathological findings and local tumor-infiltrating macrophages in prostatectomy specimens. METHODS: Preoperative peripheral blood monocyte counts were retrospectively assessed for their associations with pathological findings (pathological T stage, Gleason Score, extraprostatic extension, seminal vesicle invasion, and surgical margin) and biochemical recurrence of 248 patients who underwent radical prostatectomy. Local tumor-infiltrating macrophages were also evaluated immunohistochemically for their association with peripheral monocyte counts. RESULTS: The peripheral monocyte counts of the patients with extraprostatic extension, seminal vesicle invasion, or primary Gleason ≥4 were significantly higher than those of the patients without each of these pathological findings (P < 0.001, P = 0.034, and P = 0.004, respectively). Peripheral monocyte count was a significant predictor of adverse pathology and postoperative biochemical recurrence in localized prostate cancer by multivariate analysis (P = 0.001 and P = 0.041, respectively). Both the density and the count of tumor-infiltrating macrophages correlated significantly with the peripheral blood monocyte count (Spearman rank correlation coefficients were 0.463 and 0.649, respectively, P < 0.001). CONCLUSIONS: Peripheral blood monocyte count reflecting local tumor-infiltrating macrophages was a predictive factor for tumor progression and prognosis in patients with localized prostate cancer. Elucidating the mechanism of the interaction of peripheral monocytes with tumor-infiltrating macrophages is necessary.


Assuntos
Macrófagos/patologia , Próstata/patologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata , Idoso , Contagem de Células Sanguíneas/métodos , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Monócitos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Glândulas Seminais
15.
Hinyokika Kiyo ; 60(4): 175-8, 2014 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-24882229

RESUMO

A 63-year-old man who had undergone radical cystectomy and ileal conduit formation for invasive bladder cancer 3 years before presented with continuous positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette-Guérin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in 100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of another catheter was effective for continuing the therapy. Urinary cytology in the left upper urinary tract and the ileal conduit became negative after the therapy. There was no evidence of recurrence or metastasis of urothelial carcinoma 6 months after the therapy.


Assuntos
Vacina BCG/administração & dosagem , Carcinoma in Situ/terapia , Derivação Urinária , Neoplasias Urológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Neoplasias da Bexiga Urinária/terapia
16.
Hinyokika Kiyo ; 60(6): 299-301, 2014 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-25001648

RESUMO

Leiomyosarcomas of the spermatic cord are rare tumors which cause significant morbidity and mortality. We report a case of leiomyosarcoma in a 67-year-old man who presented with a left scrotal mass. Left orchiectomy with high ligation of the spermatic cord was performed with clinical diagnosis of scrotal tumor. The pathological examination revealed leiomyosarcoma arising from the spermatic cord. He was free of disease two years postoperatively.


Assuntos
Neoplasias dos Genitais Masculinos/patologia , Leiomiossarcoma/patologia , Cordão Espermático , Idoso , Humanos , Masculino
17.
Nihon Hinyokika Gakkai Zasshi ; 105(2): 37-42, 2014 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-24908814

RESUMO

OBJECTIVE: We analyzed the efficacy of ethinylestradiol as estrogen therapy on Castration-resistant Prostate Cancer (CRPC). PATIENTS AND METHODS: The study was conducted on 14 patients who were diagnosed as having CRPC and who were being prescribed ethinylestradiol (1.5-2.0 mg/day) with aspirin (100 mg/day) and an LH-RH agonist in our hospital from August 2011. RESULTS: All patients had already been treated with a combined androgen blockade (CAB), 8 patients had been treated with docetaxel, 9 patients with tegafur-uracil, 4 patients with estramustine phosphate sodium. Age and prostate-specific antigen (PSA) at prescription of ethinylestradiol was 55-85 (median 75.5) and 0.784-508.7 ng/ml (median 4.842 ng/ml). Thirteen patients (92.9%) achieved a decline in PSA, 8 patients (57.1%) achieved a decline in PSA > 50%. Time to progression was 0-18 months (median 7 months), and there were no severe adverse events including venous thromboembolic diseases. CONCLUSION: Oral ethinylestradiol administration may have efficacy for CRPC without severe adverse events. Ethinylestradiol may be one of the selective drugs for CRPC patients who do not wish to undergo intravenous chemotherapy or become resistant to docetaxel.


Assuntos
Estrogênios/uso terapêutico , Etinilestradiol/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estrogênios/administração & dosagem , Etinilestradiol/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
18.
bioRxiv ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39282407

RESUMO

Sensorimotor learning can change the tuning of neurons in motor-related brain areas and rotate their preferred directions (PDs). These PD rotations are commonly interpreted as reflecting motor command changes; however, cortical neurons that display PD rotations also contribute to sensorimotor learning. Sensorimotor learning should, therefore, alter not only motor commands but also the tuning of neurons responsible for this learning, and thus impact subsequent learning ability. Here, we investigate this possibility with computational modeling and by directly measuring adaptive responses during sensorimotor learning in humans. Modeling shows that the PD rotations induced by sensorimotor learning, predict specific anisotropic changes in PD distributions that in turn predict a specific spatial pattern of changes in learning ability. Remarkably, experiments in humans then reveal large, systematic changes in learning ability in a spatial pattern that precisely reflects these model-predicted changes. We find that this pattern defies conventional wisdom and implements Newton's method, a learning rule where the step size is inversely proportional rather than proportional to the learning gradient's amplitude, limiting overshooting in the adaptive response. Our findings indicate that PD rotation provides a mechanism whereby the motor system can simultaneously learn how to move and learn how to learn.

19.
Int Cancer Conf J ; 13(1): 26-32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38187183

RESUMO

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5 months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21 months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9 months after surgery.

20.
Cancer Med ; 13(18): e70249, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39315676

RESUMO

INTRODUCTION: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness. METHODS: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed. RESULTS: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population. CONCLUSION: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Masculino , Feminino , Neoplasias/genética , Neoplasias/terapia , Japão , Pessoa de Meia-Idade , Idoso , Medicina de Precisão/métodos , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Adulto Jovem , Genômica/métodos , Resultado do Tratamento , Biomarcadores Tumorais/genética
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