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Hayakazu Nakazawa

Publications and source records attributed to Hayakazu Nakazawa.

17 recordsLinked to original sources
PubMed2006

Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study.

PURPOSE: Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (gammadelta) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated gammadelta T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study. EXPERIMENTAL DESIGN: Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous gammadelta T cells every week or every 2 weeks, 6-12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis. RESULTS: Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of gammadelta T cells in peripheral blood and also a high response to the antigen in vitro. CONCLUSIONS: The results indicated that adoptive immunotherapy using in vitro-activated autologous gammadelta T cells was well tolerated and induced anti-tumor effects.

Adolescent↗
PubMed2006

[Gynecomastia].

Explore the source record for details and available documents.

Androgens↗
PubMed2006

Favorable prognosis of renal cell carcinoma with increased expression of chemokines associated with a Th1-type immune response.

The potential role of chemokines in clinical tumors remains poorly understood. Recent investigations have shown the differential expression of chemokine receptors on lymphocytes mediating Th1- and Th2-type immune responses. We examined Th1- and Th2-associated cytokines and chemokines, as well as the expression of their receptors in tumor-infiltrating lymphocytes in renal cell carcinoma (RCC). Sixty-seven patients with sporadic RCC were analyzed for the expression of Th1- and Th2-associated genes using real-time polymerase chain reaction. Tumor infiltration by CXC chemokine receptor 3 (CXCR3)-positive and CC chemokine receptor 5 (CCR5)-positive cells was detected by immunohistochemistry and by flow cytometry. The expression of Th1-associated genes was significantly increased in tumors compared to normal kidney tissues. The expression of interferon-gamma correlated positively with that of Th1 chemokines. Tumors expressing higher Th1 chemokines did not recur after curative surgery. Multivariate analysis showed that increased monokine induced by interferon (IFN)-gamma (MIG) expression was an independent favorable prognostic factor. Immunohistochemistry showed that the degree of CXCR3-positive cell infiltration significantly correlated with IFN-gamma inducible protein 10, MIG and IFN-gamma-inducible T cell a chemoattractant expression (I-TAC). Flow cytometric analysis showed increased expression of CXCR3 and CCR5 in tumor-infiltrating T lymphocytes compared to that in peripheral blood T cells. These results suggest that upregulation of the Th1-type immune response in RCC tumors with a favorable prognosis may be mediated by Th1-associated chemokines. Integrity of the Th1-type immune response seems to be required for tumor regression, suggesting that detection and correction of a defect in the Th1-type response cascade would thus be one of the main targets for tailor-made immunotherapy and gene therapy in RCC.

Aged↗
PubMed2006

[Clinico-pathological investigation of upper urinary tract tumors in patients with normal renal function and in patients with end stage renal disease].

AIMS: To clinically investigate upper urinary tract tumors in end stage renal disease (ESRD) patients. PATIENTS AND METHODS: Between 1988 and 2003, a study was made of 153 patients who underwent surgical treatment for upper urinary tract tumors in the Department of Urology, Tokyo Women's Medical University. Of these, 10 had ESRD while 143 had normal renal function. Comparisons were made of the following variables between the two groups: patient's background, clinical findings, surgical procedures, pathological findings, prognosis, depth of tumor cell invasion, tumor grades, postoperative survival rates, cancer-specific survival rates, and complications. RESULTS: Ten ESRD patients with upper urinary tract tumors were comprised of 5 males and 5 females with a median age of 59 (40-71) years and an average hemodialysis period of 71 (0-279) months. Macroscopic hematuria appeared in seven cases (70%) at the onset, and tumors occurred at the renal pelvis in nine cases (90%). As to the T stage, seven cases (70%) were pT2 or more and all 10 cases (100%) exhibited grade 2 or higher in ESRD patients, yielding no significant differences with the cases of normal renal function. In addition, there was no significant difference in both groups with respect to postoperative survival rates and cancer-specific survival rates in cases with curative resection. CONCLUSION: Although upper urinary tract tumors had been considered to exhibit higher grades and stages of malignancy in ESRD cases than in those with normal renal function, the present results showed that the clinico-pathological features are similar in both patients groups. Given that there was no significant difference in postoperative survival rates and cancer-specific survival rates, radical surgery should be also indicated, if possible, for the ESRD patients with upper urinary tract tumors as well as the patients with normal renal function.

Adult↗
PubMed2004

Hypermethylation of the CpG island of connexin 32, a candiate tumor suppressor gene in renal cell carcinomas from hemodialysis patients.

Long duration of patients on hemodialysis is a large risk for the development of renal cell carcinoma (RCC) compared to general patients. However, the carcinogenic process is still unclear. On the other hand, we have reported that connexin (Cx) 32, a molecule of gap junction, is a new tumor suppressor gene in human RCC. In this study, we investigated the clinical significance of methylation-dependent silencing of Cx32 gene in the development of the RCC from the hemodialysis patients. As the result, we found that the inactivation of Cx32 through hypermethylation of the promoter regions frequently occurred in non-cancerous regions as well as cancerous regions of kidneys from hemodialysis patients. However, the hypermethylation of Cx32 occurred only in cancerous regions but not non-cancerous regions of kidneys from the general patients without hemodialysis. Furthermore, the hypermethylation of RASSAF1A, a representative tumor suppressor gene in human RCC, occurred in cancerous regions but not non-cancerous regions of kidneys from the hemodialysis and general patients. These results suggest that Cx32 is a promising tumor suppressor gene relating to the early stage of renal carcinogenesis in the hemodialysis patients.

Carcinoma, Renal Cell↗
PubMed2004

Radical cystectomy for invasive bladder cancer: results of multi-institutional pooled analysis.

BACKGROUND: We report the outcome of radical cystectomy for patients with invasive bladder cancer, who did not have regional lymph node or distant metastases, at 21 hospitals. METHODS: Retrospective, non-randomized, multi-institutional pooled data were analyzed to evaluate outcomes of patients who received radical cystectomy. Between 1991 and 1995, 518 patients with invasive bladder cancer were treated with radical cystectomy at 21 hospitals. Of these, 250 patients (48.3%) received some type of neoadjuvant and/or adjuvant therapy depending on the treatment policy of each hospital. RESULTS: The median follow-up period was 4.4 years, ranging from 0.1 to 11.4 years. The 5-year overall survival rate was 58% for all 518 patients. The 5-year overall survival rates for patients with clinical T2N0M0, T3N0M0 and T4N0M0 were 67%, 52% and 38%, respectively. The patients with pT1 or lower stage, pT2, pT3 and pT4 disease without lymph node metastasis had 5-year overall survivals of 81%, 74%, 47% and 38%, respectively. The patients who were node positive had the worst prognosis, with a 30% overall survival rate at 5 years. Neoadjuvant or adjuvant chemotherapy did not provide a significant survival advantage, although adjuvant chemotherapy improved the 5-year overall survival in patients with pathologically proven lymph node metastasis. CONCLUSIONS: The current retrospective study showed that radical cystectomy provided an overall survival equivalent to studies reported previously, but surgery alone had no more potential to prolong survival of patients with invasive cancer. Therefore, a large-scale randomized study on adjuvant treatment as well as development of new strategies will be needed to improve the outcome for patients with invasive bladder cancer.

Adult↗
PubMed2004

Tumor doubling time of renal cell carcinoma measured by CT: collaboration of Japanese Society of Renal Cancer.

OBJECTIVE: This study was conducted to examine the natural history of renal cell carcinoma (RCC). METHODS: Inclusion criteria were the following: (1) patients who received diagnostic imaging of the kidney (CT, MRI) at two points in time before the diagnosis of RCC or patients who were followed, without treatment, after a diagnosis of RCC; and (2) patients in whom changes in tumor size were followed by the same modality of diagnostic imaging and who did not receive any treatment which could exert anti-tumor activity on the primary or metastatic lesions. The tumor doubling time (DT) and the growth rate of maximum tumor diameter (R) were determined. DT was calculated using the equation DT = (T - T(0)) x log2/logV - logV(0) (where T - T(0) indicates the length of time between two measurements and V(0) and V denote the tumor volume at two points of measurement). R was calculated using the equation R = (phi - f(0))/(T - T(0)) x 100 (where phi(0) and f indicate the maximum diameter at two points). Fifty-six cases registered with the Japanese Society of Renal Cancer were included in the evaluation. RESULTS: DT was 603.1 +/- 510.1 days, which did not correlate with V(0). R was 0.263 +/- 0.346 cm/day x 100. In cases where the tumor diameter was >/=4 cm, a significant correlation was noted between f(0) and R. CONCLUSIONS: Elucidation of the natural history of RCC will contribute to facilitation of differential diagnosis and determination of optimum therapeutic strategy.

Adult↗
PubMed2004

High expression of chemokine gene as a favorable prognostic factor in renal cell carcinoma.

PURPOSE: The presence and potential role of chemokines in clinical tumors remain poorly understood. Chemokines are a large family of chemoattractant cytokines with several members that are also able to regulate angiogenesis. We hypothesized that chemokines may have an important role in regulating tumor growth in renal cell carcinoma (RCC). To begin to test this hypothesis chemokine gene expression and its influence on prognosis, cellular infiltration and angiogenesis in RCC were examined. MATERIALS AND METHODS: A total of 51 patients with sporadic RCC were analyzed for the expression of the 7 chemokine genes interleukin-8, gamma-interferon inducible protein-10 (IP-10), monokine induced by gamma-interferon (MIG), macrophage chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated and activated normal T cells excreted and secreted (RANTES) using semiquantitative reverse transcriptasepolymerase chain reaction. Lymphocyte infiltration and microvessel density were determined immunohistochemically by staining CD8 and CD34 cells, respectively. RESULTS: : The expression of IP-10, MIG, MIP-1beta and RANTES was significantly increased in tumor compared to normal kidney tissues. The expression of IP-10, MIG and MIP-1beta showed an inverse correlation with tumor size. Stages 1 to 3 tumors expressing high levels of IP-10, MIG, MIP-1beta and RANTES did not recur after curative surgery. Intratumor expression of IP-10, MIG and MIP-1beta showed a positive correlation with the degree of CD8 cell infiltrating in the tumor and an inverse correlation with microvessel density. CONCLUSIONS: These results suggest that IP-10, MIG and MIP-1beta are expressed at high levels in tumors that rarely recur after surgery. The antitumorigenic effect of IP-10, MIG and MIP-1beta may result from the recruitment of lymphocyte infiltration and/or inhibition of angiogenesis in RCC. The amplification of chemokine expression by immunotherapy or gene therapy may be a practical and effective strategy to promote tumor regression.

Carcinoma, Renal Cell↗
PubMed2004

Spoke-wheel-like enhancement as an important imaging finding of chromophobe cell renal carcinoma: a retrospective analysis on computed tomography and magnetic resonance imaging studies.

AIM: Little information has been reported with regard to the radiological features of chromophobe cell renal carcinomas (CCRC). The aim of the present study was to identify imaging characteristics which lead to the histological diagnosis of CCRC. METHODS: The imaging findings of computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed in 11 patients with CCRC operated on at Tokyo Women's Medical University, Tokyo, Japan. RESULTS: None of the factors studied were significant in distinguishing the two variants, typical and eosinophilic variants. Enhanced CT scans showed a spoke-wheel-like enhancement with a central scar in 3 patients (27%). The radiological patterns were classified into two groups. Seven patients (64%) showed pattern 1 in which: (i) a hypodense to isodense enhancement compared to the renal medulla in the corticomedullary phase during dynamic CT; (ii) an isodense mass compared to the renal medulla in unenhanced CT scan; and (iii) a lobulated appearance were typically observed. Four patients (36%) showed pattern 2 that seemed to be similar to the features of clear cell carcinoma, having an alveolar structure including a hyperdense enhancement in the corticomedullary phase and an inhomogeneous appearance. A spoke-wheel-like enhancement was observed only in patients with pattern 1, and was more clearly demonstrated in larger tumors. CONCLUSIONS: The CT and MRI findings in CCRC patients were not uniform, but it was noted that a spoke-wheel-like enhancement with a central stellate scar, which might have been mistaken for oncocytoma, was one of important findings of CCRC. Tumors demonstrating a spoke-wheel-like enhancement with a central scar should be carefully managed, because they could be malignant.

Adult↗
PubMed2004

[The clinical efficacy of Bladder Chek NMP22 in urothelial cancer].

The purpose of this study is to investigate the clinical efficacy of a quick test for NMP22 (Nuclear Matrix Protein 22), Bladder Chek NMP22, as a screening test for urothelial cancers. The subjects include 51 cases(43 cases with pathologically confirmed bladder cancer, and 8 cases with upper urothelial cancer). Bladder Chek NMP22 revealed false positive in the urine with more than 1 x 10(5)/microliter of erythrocytes and 1 x 10(3)/microliter of white blood cells. Thus, showing that Bladder Chek NMP22 was not relatively affected by the contaminated erythrocytes and white blood cells, compared with other conventional methods to detect urinary malignant disease. In 51 cases diagnosed of having pathologically urothelial cancers, the sensitivity of Bladder Chek NMP22 was 56.8%. Bladder Chek NMP22 demonstrated more excellent sensitivity than the other methods. The positivity of Grade3 patients was 68.4%, 68.4% and 63.2% by Bladder Chek NMP22, NMP22 ELISA and urinary cytology. In contrast, the positivity rate for the patients with Grade1 stage was 58.3%, 33.3% and 8.3%. There is no significance of positivity rate between each examination in patients with high grade cancer. However Bladder Chek NMP22 demonstrated the higher positivity in patients with low grade cancer. Bladder Chek NMP22 test could be an easy and confidential method to detect urothelial cancers, especially with low grade, as a screening examination.

Biomarkers, Tumor↗
PubMed2002

Nephron-sparing tumorectomy for a large benign renal mass: a case of massive bilateral renal angiomyolipomas associated with tuberous sclerosis.

A case of massive bilateral angiomyolipomas (AML) associated with tuberous sclerosis in a 33-year-old woman is reported. She was hospitalized because she had been experiencing abdominal fullness and epigastralgia. Several imaging studies revealed massive bilateral renal tumors and she was diagnosed as having renal AML associated with tuberous sclerosis. Left nephrectomy was carried out after renal arterial embolization for intratumor hemorrhage. Two years after left nephrectomy, nephron-sparing surgery (tumorectomy) for right AML was done because of an increase in the size of the right renal AML and she hoped for a future pregnancy. The left kidney with AML weighed 5700 g and the right AML weighed 1700 g. Postoperative serous creatinine did not differ from that before operation and an increase in the size of the residual tumor was not observed 8 months after operation. We consider that tumorectomy is an effective therapy in patients with a very large tumor involving a solitary kidney.

Adult↗
PubMed2002

Impact of arterial occlusion during partial nephrectomy on residual renal function: an evaluation with (99m)technetium-dimercaptosuccinic acid scintigraphy.

BACKGROUND: Partial nephrectomy (PNx) has been performed with temporary renal arterial occlusion and in situ renal hypothermia (conventional PNx). However, the impact of temporary renal arterial occlusion on residual renal function has not been well assessed. To address this question, we performed renal scintigraphy with (99m)technetium-dimercaptosuccinic acid (DMSA) for the quantitative measurement of postoperative residual renal function after conventional PNx and partial nephrectomy without arterial occlusion (non-clamping PNx). METHODS: Thirty-four patients underwent postoperative DMSA scintigraphy after PNx for renal cell carcinoma. No obvious difference in preoperative renal function between the diseased kidney and the contralateral kidney was found in any of the patients. Of these patients, 24 underwent conventional PNx, and 10 underwent non-clamping PNx. Residual renal function was evaluated using the relative DMSA uptake of the operated kidney. RESULTS: The relative DMSA uptake of the operated kidney was 39.9 +/- 7.3% (25.1-58.8) after conventional PNx compared to 34.8 +/- 8.9% (13.5-45.5) after non-clamping PNx. This difference was not statistically significant (P = 0.15). Total ischemic time during conventional PNx had no adverse influence on the residual renal function. In the analysis of the other determinant factors influencing residual renal function, tumor size was the only significant factor that inversely correlated with the relative DMSA uptake. CONCLUSION: Our results showed that arterial clamping during PNx has no negative impact on the functional residual capacity as long as insitu renal hypothermia is adequately performed.

Adult↗
PubMed2002

[A case of focal xanthogranulomatous pyelonephritis difficult to differentiate from renal cell carcinoma].

A 34-year-old female with left flank pain persisting for 3 months consulted us on 19 Feb, 2001. Ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and renal angiography revealed a cystic renal tumor in the upper pole of the left kidney invading the spleen, and paraaortic lymph node swelling. Left radical nephrectomy combined with splenectomy and partial diaphragmectomy was performed under a tentative diagnosis of renal cell carcinoma. However, histopathological findings revealed xanthogranulomatous pyelonephritis (XGP). XGP is a rare, severe, chronic inflammatory disease characterized by accumulation of lipid laden macrophages. XGP is classified as diffuse or focal type. Preoperative diagnosis of focal XGP is difficult because of radiological similarities to renal cell carcinoma. Our case was more difficult to diagnose because she showed few signs of inflammation and had no history of urinary tract infection or stones.

Adult↗