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1.
Tohoku J Exp Med ; 259(3): 229-236, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36596503

RESUMO

Poor prognostic cardiac function is known among some patients with primary aldosteronism (PA). However, studies with echocardiograms on whether the normalization of aldosterone after laparoscopic adrenalectomy (LADX) improves myocardial hypertrophy and diastolic cardiac dysfunction have been inadequate. Between August 2009 and December 2021, 147 patients with unilateral PA who underwent pre- and post-LADX echocardiography at a single center were enrolled in this retrospective study. We evaluated the cardiac impact of LADX by comparing patients who demonstrated complete clinical success (CS) with those who demonstrated partial or absent CS. Adjusted odds ratios (ORs) for not obtaining complete CS were calculated using binomial logistic regression analysis for clinically significant items among the pre- and postoperative clinical and echocardiographic markers. Overall, 47 (29%) and 104 (71%) patients had complete and partial or absent CS, respectively. Compared to patients with complete CS, patients with partial CS or without CS tended to have preoperative low early to late diastolic transmitral flow velocity (E/A) (< 0.8 cm/s) (41% vs. 21%, P < 0.05) and postoperative supranormal left ventricular ejection fraction (LVEF) (> 70%) (37% vs. 21%, P < 0.05). Furthermore, laparoscopic adrenalectomy improved the low and high echocardiographic values of E/A and LVEF, respectively, in both groups. The risk factors for not reaching complete CS were male sex (OR 3.42), low preoperative E/A (OR 3.11), and postoperative supranormal LVEF (OR 3.17). Although low preoperative E/A and postoperative supranormal LVEF are associated with poor clinical outcomes, LADX can improve diastolic cardiac function in patients with PA.


Assuntos
Cardiopatias , Hiperaldosteronismo , Humanos , Masculino , Feminino , Adrenalectomia , Volume Sistólico , Estudos Retrospectivos , Hiperaldosteronismo/complicações , Função Ventricular Esquerda , Cardiopatias/complicações , Cardiopatias/cirurgia
2.
Cancer Sci ; 113(1): 182-194, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34710258

RESUMO

To improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre- and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre- and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2-hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence-free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Metabolômica/métodos , Recidiva Local de Neoplasia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Renais/urina , Linhagem Celular Tumoral , Cromatografia Líquida , Feminino , Humanos , Neoplasias Renais/urina , Modelos Logísticos , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/urina , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Resultado do Tratamento
3.
Tohoku J Exp Med ; 257(2): 127-133, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35418533

RESUMO

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.


Assuntos
Hiperplasia do Linfonodo Gigante , Neoplasias Renais , Idoso , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Fluordesoxiglucose F18 , Humanos , Rim/patologia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Masculino
4.
Int J Mol Sci ; 23(12)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35743254

RESUMO

Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that α2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.


Assuntos
Colágeno Tipo I , Escleroderma Sistêmico , Animais , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Fibroblastos/metabolismo , Fibrose , Camundongos , Escleroderma Sistêmico/metabolismo , Pele/metabolismo
5.
Int J Urol ; 28(1): 69-74, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33131119

RESUMO

OBJECTIVE: To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS: A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS: Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001). CONCLUSION: Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Ejaculação , Humanos , Excisão de Linfonodo , Masculino , Espaço Retroperitoneal , Sobreviventes , Neoplasias Testiculares/cirurgia
6.
Cancer Sci ; 111(7): 2570-2578, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32350988

RESUMO

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography-mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l-glutamic acid, lactate, d-sedoheptulose 7-phosphate, 2-hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l-kynurenine, l-glutamine, fructose 6-phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/urina , Neoplasias Renais/diagnóstico , Neoplasias Renais/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cromatografia Líquida , Comorbidade , Feminino , Humanos , Masculino , Metaboloma , Metabolômica/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
7.
Tohoku J Exp Med ; 252(1): 1-8, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814720

RESUMO

Carbohydrate antigens are associated with carcinogenesis, cancer invasion, and metastasis and their expression reflect biological activities of various cancers. We previously reported that expression of disialosyl globopentaosyl ceramide (DSGb5), one of carbohydrate antigens, in radical prostatectomy specimens independently predicted biochemical recurrence (i.e., elevating serum prostate specific antigen without recurrent lesions in the image) after radical prostatectomy. However, it is important to evaluate the prognosis at the diagnosis. In this study we investigated DSGb5 expression in prostate biopsy specimens to develop a novel biomarker for providing appropriate management. Between 2005 and 2011, patients who underwent both prostate biopsy and radical prostatectomy in our institution were included. The median follow-up period was 88 months. DSGb5 expression was assessed by immunohistochemical staining and defined 116 patients as high DSGb5 expression (42 patients) or low DSGb5 expression (74 patients). High DSGb5 expression was significantly associated with lymphovascular invasion in radical prostatectomy specimens on both univariate and multivariable analyses (p = 0.028, 0.027). On multivariable analysis, Gleason Score in prostatectomy specimen, positive resection margin, and DSGb5 expression in the biopsy specimen were independently associated with biochemical recurrence-free survival following radical prostatectomy (p = 0.004, 0.008, 0.024). When targeting only patients with negative resection margin, DSGb5 expression was significantly associated with biochemical recurrence-free survival on both univariate and multivariable analyses (p = 0.006, 0.007). DSGb5 expression in prostate biopsy specimens is predictive of lymphovascular invasion and biochemical recurrence-free survival following radical prostatectomy. DSGb5 is a potential biomarker for preoperatively predicting oncological outcomes of prostate cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Globosídeos/metabolismo , Recidiva Local de Neoplasia/patologia , Próstata/metabolismo , Próstata/patologia , Prostatectomia , Idoso , Biópsia , Intervalo Livre de Doença , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Próstata/cirurgia
8.
Int J Cancer ; 145(2): 484-493, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30628065

RESUMO

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G-Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G-Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G-Met protocol.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Metabolômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos de Casos e Controles , Cromatografia Líquida , Ciclo do Ácido Cítrico , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Transdução de Sinais , Espectrometria de Massas em Tandem
9.
Prostate ; 79(5): 536-543, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30593704

RESUMO

BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.


Assuntos
Isquemia/complicações , Inibidores da Fosfodiesterase 5/farmacologia , Próstata/irrigação sanguínea , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/etiologia , Animais , Modelos Animais de Doenças , Isquemia/tratamento farmacológico , Isquemia/patologia , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Tadalafila/farmacologia
10.
Tohoku J Exp Med ; 248(1): 31-36, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31092738

RESUMO

Aldosterone affects various systems and organs, including the cardiovascular system, through mineralocorticoid receptors. We here report a primary aldosteronism patient with severe cardiac dysfunction who showed dramatic improvement after laparoscopic adrenalectomy. The 57-year-old man presented with acute heart failure exacerbation. Performance status was 4, and New York Heart Association classification was 4. Echocardiography showed diffuse hypokinetic wall motion with an ejection fraction of 20%. The patient was found to have a high plasma level of brain natriuretic peptide (4,935 pg/mL), hypokalemia (2.7 mEq/L), an extremely elevated plasma aldosterone concentration (1,804 pg/mL), and high aldosterone-to-renin ratio [plasma aldosterone concentration (pg/mL)/plasma renin activity (ng/mL/hr)] (9,002). Computed tomography revealed a tumor 42 mm in diameter in the right adrenal gland. Primary aldosteronism was diagnosed with adrenal venous sampling. Medical treatment for heart failure was continued for several months, but the cardiac function was not sufficiently improved, suggesting the indication of heart transplantation. However, the patient could not be considered a candidate because of the adrenal tumor. Laparoscopic adrenalectomy was therefore performed. Immediately after surgery, echocardiography showed improved wall motion with an ejection fraction of 36%. Performance status and New York Heart Association classification were improved to 0 and 2, respectively. The present case has shown the efficacy of laparoscopic adrenalectomy for primary aldosteronism patients with severe heart failure.


Assuntos
Adrenalectomia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Testes de Função Cardíaca , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/cirurgia , Laparoscopia , Biópsia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Hormônios/metabolismo , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Radiografia Torácica , Fatores de Tempo
13.
Glycoconj J ; 34(2): 267-273, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28205070

RESUMO

Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from tissue extracts of renal cell carcinoma (RCC) with metastasis. Previous in vitro experiments have suggested that DSGb5 promotes metastasis by enhancing the migration of RCC cells and downregulating NK cell cytotoxicity against RCC cells. In this study, we investigated the clinicopathological significance of DSGb5 expression in RCC and outcomes of RCC patients. A total of 156 RCC patients who underwent surgical treatments at our hospital from January 2007 through December 2012 were analyzed in this study. The expression of DSGb5 in RCC specimens was examined by immunohistochemical staining with monoclonal antibody 5F3. The immunostaining intensity of RCC tissues was assessed in comparison with that in benign renal tubules as an internal positive control. The relationship between DSGb5 expression and clinicopathological characteristics was investigated and recurrence free survival following surgery was evaluated. Microvascular invasion was observed in 68% (n = 19/28) and in 45% (n = 58/128) of the DSGb5 high expression group and low expression group, respectively (p = 0.031). Of 156 patients with a median follow up of 51 months, 18 patients (12%) developed metastasis following surgery. Patients in the DSGb5 high expression group showed significantly lower recurrence-free survival as compared with those in the DSGb5 low expression group (log-rank P = 0.047). In the present study, DSGb5 expression was associated with microvascular invasion in RCC tissues, and patients with DSGb5 high expression showed significantly lower recurrence-free survival rates. These findings suggest that DSGb5 expressed in RCC is correlated with metastasis and is a potential predictor for identifying patients who experience metastasis after surgery.


Assuntos
Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Globosídeos/biossíntese , Neoplasias Renais , Túbulos Renais Distais , Idoso , Anticorpos Monoclonais Murinos/química , Antineoplásicos Imunológicos/química , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Túbulos Renais Distais/metabolismo , Túbulos Renais Distais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Taxa de Sobrevida
14.
Tohoku J Exp Med ; 236(1): 1-7, 2015 05.
Artigo em Inglês | MEDLINE | ID: mdl-25864532

RESUMO

About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no significant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the significantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no significant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability.


Assuntos
Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Movimento Celular , Globosídeos/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células , Separação Celular , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Globosídeos/química , Humanos , Neoplasias Renais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção
15.
Urol Int ; 92(1): 122-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24281158

RESUMO

Renal cell carcinoma (RCC) during pregnancy is rare, and the treatment of this condition requires appropriate steps to treat both the patient and the fetus. To the best of our knowledge, this is the first report to describe a case of RCC with tumor thrombus in the inferior vena cava (IVC) occurring during pregnancy. The affected 46-year-old pregnant woman with placenta previa was clinically diagnosed with cT3bN0M0 RCC at 25 weeks gestation. Therapeutic considerations included risk of sudden pulmonary embolism, risk of thrombosis or intraoperative hemorrhage, and safe delivery of the fetus. After extensive consultation with obstetricians and pediatricians, the surgical management was divided into two steps. First, the patient underwent Caesarean section and simultaneous hysterectomy at 26 weeks gestation. Then, 16 days after delivery, when hemodynamics and hemostasis had improved due to termination of gestation, the patient underwent radical nephrectomy with concomitant IVC thrombectomy.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Células Neoplásicas Circulantes/patologia , Complicações Neoplásicas na Gravidez/patologia , Veia Cava Inferior/patologia , Trombose Venosa/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Idade Gestacional , Humanos , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Nefrectomia , Gravidez , Trombectomia , Fatores de Tempo , Veia Cava Inferior/cirurgia , Trombose Venosa/cirurgia
16.
Metabolites ; 14(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38535330

RESUMO

Tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of advanced renal cell carcinoma (RCC). However, there is a lack of useful biomarkers for assessing treatment efficacy. Through urinary metabolite analysis, we identified the metabolites and pathways involved in TKI resistance and elucidated the mechanism of TKI resistance. To verify the involvement of the identified metabolites obtained from urine metabolite analysis, we established sunitinib-resistant RCC cells and elucidated the antitumor effects of controlling the identified metabolic pathways in sunitinib-resistant RCC cells. Through the analysis of VEGFR signaling, we aimed to explore the mechanisms underlying the antitumor effects of metabolic control. Glutamine metabolism has emerged as a significant pathway in urinary metabolite analyses. In vitro and in vivo studies have revealed the antitumor effects of sunitinib-resistant RCC cells via knockdown of glutamine transporters. Furthermore, this antitumor effect is mediated by the control of VEGFR signaling via PTEN. Our findings highlight the involvement of glutamine metabolism in the prognosis and sunitinib resistance in patients with advanced RCC. Additionally, the regulating glutamine metabolism resulted in antitumor effects through sunitinib re-sensitivity in sunitinib-resistant RCC. Our results are expected to contribute to the more effective utilization of TKIs with further improvements in prognosis through current drug therapies.

17.
Drug Discov Ther ; 17(1): 70-72, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36843077

RESUMO

We studied 95 patients with infantile hemangioma (IH) treated with propranolol at the Department of Dermatology, Kumamoto University Hospital, from November 2016 to January 2022, based on sex, site, clinical classification, duration of treatment, and residual lesions after treatment. Four of the 95 patients discontinued propranolol due to side effects, and 55 completed follow-ups at our hospital. We observed that 30.1% showed complete resolution of the skin rash, while the remaining 69.8% had erythema or atrophic scarring. Complete resolution occurred in 70% of the cases with the subcutaneous type but only in 15% with the tumor type. Seventeen of the 55 patients who completed follow-ups were treated with propranolol combined with laser therapy. Combined use of propranolol and laser therapy significantly reduced severe erythema compared to the propranolol monotherapy. These results suggest that propranolol therapy in IH often leaves erythema except in the subcutaneous type and that an improvement in erythema can be expected when propranolol is combined with laser therapy.


Assuntos
Hemangioma , Terapia a Laser , Neoplasias Cutâneas , Humanos , Lactente , Propranolol/uso terapêutico , Hemangioma/tratamento farmacológico , Resultado do Tratamento , Eritema/tratamento farmacológico , Administração Oral , Neoplasias Cutâneas/tratamento farmacológico
18.
Case Rep Oncol ; 16(1): 1573-1578, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089733

RESUMO

Although the response to combination therapy has been reported in patients with brain metastases from advanced renal cancer, treatment-related cerebral hemorrhage has not been adequately studied. The CheckMate 9ER clinical trial of nivolumab and cabozantinib excluded patients with brain metastases. Therefore, the associated treatment outcomes in these patients with brain metastases are unclear. Herein, we report a case of bleeding from brain metastases in a patient with advanced renal cancer after gamma knife combination therapy with nivolumab and cabozantinib. Fortunately, the cerebral hemorrhage of the patient was alleviated by conservative treatment. Despite treatment interruption, the metastatic lesions reduced in size, and treatment was gradually resumed. In this case study, we report the risk of cerebral hemorrhage in combination therapy for brain metastasis cases, how to manage hemorrhage cases, and their prognosis.

19.
Anticancer Res ; 43(11): 5115-5125, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37909950

RESUMO

BACKGROUND/AIM: This retrospective study aimed to investigate the outcomes of relapse-free survival (RFS) after salvage radiation therapy (SRT) to the prostate bed for postoperative biochemical recurrence of prostate cancer. PATIENTS AND METHODS: A total of 87 patients were analyzed. There were 27, 32, and 24 patients with pathological grade groups of 1-2, 3, and 4-5, respectively. SRT doses of 64, 66 or 70 Gy were administered to 24, 3 and 60 patients, respectively. The Kaplan-Meier method was used to estimate time-to-event outcomes. The multiple imputations method was used to impute missing values, and Cox proportional-hazards models were applied for multivariate analyses. RESULTS: The median follow-up period for patients overall was 58.6 months. The 5-year RFS rates of the whole cohort was 59.4% and those for pathological grade groups 1-2, 3 and 4-5 were 88.9%, 37.7% and 39.5%, respectively. In multivariate analyses, higher pathological grade group [4-5 vs. 3 vs. 1-2: hazard radio (HR)=8.65, p<0.01], negative surgical resection margin (positive vs. negative: HR=0.41, p=0.02) and higher pre-salvage treatment serum prostate-specific antigen (cutoff value 0.31 ng/ml: HR=3.50, p<0.01) were significantly associated with poorer RFS. The cumulative incidences of grade 2 or more late rectal bleeding and late hematuria were 4.9% and 8.7%, respectively, at 5 years and 4.9% and 15.7%, respectively, at 8 years. These toxicities occurred only in the 70 Gy-treated arm. CONCLUSION: Our study revealed that pathological grade group 3 prostate cancer patients experienced moderately unfavorable RFS after SRT. Higher radiation doses might increase late toxicities without improving RFS.


Assuntos
Neoplasias da Próstata , Radioterapia (Especialidade) , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Doença Crônica , Análise Multivariada
20.
Case Rep Oncol ; 15(3): 1014-1020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36636673

RESUMO

In a rare case, free from systemic therapy, deferred cytoreductive nephrectomy was implemented in treating an advanced renal cell carcinoma with liver, lung, and splenic colon metastases. A 59-year-old man diagnosed with advanced renal cell carcinoma underwent deferred cytoreductive nephrectomy due to a partial response to systemic treatment after a period of 1 year. After the surgery, no additional treatment was implemented. Furthermore, after 10 months, the patient had no recurrence of renal cell carcinoma. Through a review of this case and deferred cases in the current literature, we could emphasize the importance of image evaluation and pathological findings as an indication for surgery and subsequent treatment options. However, there is room for debate with regards to the indications for deferred cytoreductive nephrectomy as well as a therapeutic strategy after the surgery. This report discusses the significance of deferred cytoreductive nephrectomy in terms of prognosis and quality-of-life improvement in advanced renal cancer.

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