Biomedical subjects

Akio Horiguchi

Publications and source records attributed to Akio Horiguchi.

17 recordsLinked to original sources

PubMed2006

Increased serum leptin levels and over expression of leptin receptors are associated with the invasion and progression of renal cell carcinoma.

PURPOSE: Leptin, an adipocyte derived cytokine that is closely associated with obesity, was recently shown to be involved in carcinogenesis and cancer progression. Because obesity is a significant risk factor for renal cell carcinoma, we investigated the link between leptin and the development of renal cell carcinoma. MATERIALS AND METHODS: Associations between preoperative serum leptin levels and leptin receptor expression in tumor specimens and various clinicopathological parameters were analyzed in 57 patients with renal cell carcinoma. RESULTS: Serum leptin levels were 1.2 to 16.2 ng/ml (mean 4.5). Of 57 tumors 22 (38.6%) demonstrated high leptin receptor expression. Serum leptin levels were significantly higher in patients with vs without tumor specimen venous invasion (p = 0.030) and higher in patients with high vs low leptin receptor expression (p = 0.019). There were significant associations between high leptin receptor expression and the presence of venous invasion (p = 0.013), histological type (p = 0.0076) and regional lymph node metastasis (p = 0.047). Of 42 patients with N0M0 disease those with serum leptin 5.0 ng/ml or more had significantly shorter progression-free survival than patients with lower levels (p = 0.0043). Multivariate Cox proportional hazards model analysis demonstrated that higher serum leptin was an independent predictor of progression-free survival (p = 0.0406). CONCLUSIONS: Leptin and leptin receptor could have a key role in the invasion of renal cell carcinoma and they could be valuable predictors of progression.

Adult↗

PubMed2006

Leptin promotes invasiveness of murine renal cancer cells via extracellular signal-regulated kinases and rho dependent pathway.

PURPOSE: Obesity is a significant risk factor for renal cell carcinoma. The adipocyte derived cytokine leptin, which controls body weight homeostasis through food intake and energy expenditure, recently provided a potential link between obesity and cancer development. We examined whether leptin promotes the invasiveness of renal cancer cells and we investigated its underlying signaling pathway. MATERIALS AND METHODS: Leptin receptor expression in the 6 human renal cancer cell lines Caki-1, ACHN, 769P, A498, SKRC44 and SKRC49, and in the murine renal cancer cell line Renca was examined by reverse transcriptase-polymerase chain reaction and Western blotting. The effect of leptin on renal cancer cell invasiveness was assessed by the invasion of cells through Matrigel coated Transwell inserts. Leptin induced intracellular signaling was examined by Western blotting. RESULTS: Leptin receptor was detected in all renal cancer cells examined at the mRNA and protein levels. Leptin increased Renca cell invasiveness at 1 ng/ml (p < 0.05). There was up to 3-fold invasiveness compared to untreated cells at 100 ng/ml with the activation of extracellular signal-regulated kinases and rho guanosine triphosphatase (p < 0.01). Leptin induced activation of rho guanosine triphosphatase was inhibited not only by the rho kinase inhibitor Y27632, but also by the MEK1 inhibitor PD98059, of which each inhibited leptin induced invasion of Renca cells (p < 0.01). CONCLUSIONS: Leptin promoted the invasiveness of murine renal cancer cells via extracellular signal-regulated kinases and rho guanosine triphosphatase dependent pathways. Rho guanosine triphosphatase was a downstream effector of extracellular signal-regulated kinases in leptin induced invasion. Leptin signaling could have a key role in renal cell carcinoma invasion.

Animals↗

PubMed2006

Retroperitoneoscopic partial nephrectomy using radiofrequency ablation.

Two patients with renal tumors underwent retroperitoneoscopic partial nephrectomy. The renal tumors were initially treated with radiofrequency ablation. This method allowed tumor excision to be achieved without clamping the renal pedicle. Residual renal function was well maintained as determined by enhanced computed tomography scanning and measurement of the serum creatinine level. There were no complications such as vascular damage or collecting system injury. The pathological diagnosis was clear cell carcinoma (pT1) in Patient 1 and was not determined in Patient 2 because of entire ablation. No recurrence has been observed after 3 years and 2 years of follow up, respectively. Radiofrequency ablation was useful for control of local bleeding during retroperitonaoscopic partial nephrectomy.

Adenocarcinoma, Clear Cell↗

PubMed2006

Mucoid pseudocyst of the obturator nerve.

A 71-year-old man visited the outpatients' clinic of National Saitama Hospital, Japan, complaining of pain in the right leg. Magnetic resonance imaging (MRI) revealed a cystic mass adjacent to the right side of the urinary bladder. He underwent the removal of the cystic mass and the pathological diagnosis was a mucoid pseudocyst of the obturator nerve. After tumor resection, the pain was diminished and he has been free of disease for 3 years.

Aged↗

PubMed2005

Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.

Apoptosis↗

PubMed2005

[Clinical experience of laparoscopic adrenalectomy: the National Defense Medical College experience].

Twenty-seven laparoscopic adrenalectomies (LapAdx) were performed at the National Defense Medical College between 1999 and 2004. We evaluated the results of LapAdx (group L) compared to the results of open adrenalectomy (group O). Twenty-six of the 27 LapAdx were successfully performed, but one patient with a large pheochromocytoma required open surgey because of arterial bleeding in the renal hilus. The mean operating time in group L (185 +/- 19 min) was not significantly different from that in group O (206 +/- 13 min). The mean estimated blood loss in group L (111 +/- 61 g) was significantly lower than that in group O (308 +/- 67 g). The starting time for oral feeding and for ambulation was significantly earlier in group L than in group O. There was a major complication (intraoperative bleeding) in which a group L patient required a blood transfusion. We also compared the surgical results of 26 patients in LapAdx divided chronologically into the first half and the last half to determine the surgical skill acquired. The operating time was significantly shorter and blood loss significantly less for patients in the last half. In addition, the operating time and blood loss for the first-time LapAdx operators were comparable with those of experienced surgeons. Our results support the efficacy and the minimal invasiveness of LapAdx. The accumulated experience and knowledge regarding laparoscopic surgery in our institute were important in improving surgical procedures and results.

Adrenal Gland Neoplasms↗

PubMed2004

3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor, fluvastatin, as a novel agent for prophylaxis of renal cancer metastasis.

PURPOSE: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also called statins, are currently used widely as a safe, effective therapeutic in the treatment of hypercholesterolemia. Recently, statins have been recognized for their activity against cancer. In the present study, we examined the effect of a synthetic statin, fluvastatin, on the development of renal cancer. EXPERIMENTAL DESIGN: The effects of fluvastatin on cell viability, cell cycle, in vitro angiogenesis, and invasive properties were examined in murine renal cancer cell Renca. The changes in cell cycle-associated proteins, p21(Waf1/Cip1) and p53, and rac1 phosphorylation were analyzed by Western blotting. The prophylactic efficacy of fluvastatin to murine pulmonary metastasis of Renca was examined. RESULTS: Fluvastatin inhibited in vitro growth of Renca cells in a time- and dose-dependent manner, with up to 70% inhibition at a concentration of 10 mumol/L. This inhibitory effect was due to cell cycle arrest at the G(1) phase and induction of apoptosis accompanied by up-regulation of p21(Waf1/Cip1) and p53. The invasive properties of Renca cells through Matrigel were inhibited by fluvastatin, with decreased phosphorylation of rac1. In vitro angiogenesis was also inhibited by fluvastatin. Furthermore, oral administration at doses of 1 to 10 mg/kg/d, for 12 days after inoculation of Renca cells via the tail vein, significantly decreased the amount of pulmonary metastasis. CONCLUSIONS: Because our results suggest that fluvastatin may effectively inhibit in vitro tumor growth, invasion, angiogenesis, and metastasis of Renca cells, oral administration of fluvastatin could be a novel, safe, and effective agent for preventing metastasis of renal cancer.

Animals↗

PubMed2004

ZD1839 modulates paclitaxel response in renal cancer by blocking paclitaxel-induced activation of the epidermal growth factor receptor-extracellular signal-regulated kinase pathway.

PURPOSE: We evaluated the antitumor activity of ZD1839, a selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, in combination with paclitaxel in human renal cell carcinomas (RCCs). EXPERIMENTAL DESIGN: Eight human RCC lines and the surgical specimens obtained from 10 RCC patients were used. The protein expression was detected by Western blotting, immunohistochemistry and/or flow cytometry. Apoptosis was evaluated by flow cytometry and fragmented DNA ELISA. SKRC-49 tumor xenografts in athymic nude mice were treated with ZD1839 and/or paclitaxel, and tumor volume was determined RESULTS: EGFR protein was expressed and phosphorylated in eight RCC lines and EGFR expression was markedly increased in RCC specimens compared with adjacent normal renal tissues. Treatment of SKRC-49 with 1 micro M ZD1839 resulted in a marked decrease in the phosphorylation of EGFR but not of HER-2. Treatment of SKRC-49 with ZD1839 in combination with 5 nM paclitaxel resulted in a significant increase in apoptotic cell number compared with paclitaxel alone, whereas ZD1839 alone failed to induce apoptosis. Although administration of ZD1839 or paclitaxel resulted in a transient growth inhibition in SKRC-49 xenografts, significant tumor regrowth delay was observed when paclitaxel was combined with ZD1839. Paclitaxel phosphorylated extracellular signal-regulated kinase through EGFR activation predominantly in cancer cells. ZD1839 promoted paclitaxel-induced Bcl-2 down-regulation resulting in promoting apoptosis by blocking paclitaxel-induced activation of the EGFR-extracellular signal-regulated kinase antiapoptotic pathway independent of Akt activity in SKRC-49. CONCLUSIONS: Our findings support the idea that the significant clinical benefit is obtained from ZD1839 in combination with paclitaxel for the treatment of RCC.

Animals↗

PubMed2004

Impact of caveolin-1 expression on clinicopathological parameters in renal cell carcinoma.

PURPOSE: Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signaling pathways. Previous studies of the expression and function of caveolin-1 in cancer have shown controversial results, indicating that the physiological role of caveolin-1 varies according to cancer type. We evaluated caveolin-1 expression in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Caveolin-1 expression was evaluated by immunohistochemistry using rabbit polyclonal antibody against caveolin-1 in 60 paraffin embedded primary renal cell carcinoma specimens and 6 metastatic renal cell carcinoma specimens. When more than 50% of all cancer cell cytoplasm stained, the tumor was considered caveolin-1 positive. Associations between caveolin-1 expression, and pathological features and clinical outcomes were analyzed. RESULTS: Of 60 primary tumors 16 (26.7%) and 5 of 6 metastatic tumors (83.3%) were immunoreactive in more than 50% of cancer cells and considered caveolin-1 positive. Although no significant associations between caveolin-1 expression, pathological stage (T stage) and distant metastasis at initial presentation were observed, significant associations between positive caveolin-1 expression and high grade tumor (p = 0.0009) and regional lymph node metastasis at initial presentation (p = 0.0049) and venous invasion (p = 0.0195) were observed. There was no difference in cancer specific survival between caveolin-1 positive and negative groups. However, in 43 patients without metastasis to regional lymph nodes or a distant site at initial presentation (N0M0) the caveolin-1 positive group had significantly shorter progression-free survival than the caveolin-1 negative group (p = 0.0332). CONCLUSIONS: Caveolin-1 over expression could be a common finding in aggressive forms of renal cell carcinoma. Caveolin-1 might have an important role in the invasion and metastatic progression of renal cell carcinoma.

Adult↗

PubMed2004

[Advanced renal cell carcinoma showing a different response to two types of interferon-alpha].

Interferon (IFN)-alpha has been widely used in systemic therapy for advanced renal cell carcinoma (RCC). IFN-alpha is represented by a large family of structurally related genes expressing at least 14 subtypes, each of which shows quantitatively distinct patterns of biological activities. Although those distinct patterns of biological activities of IFN-alpha subtypes against renal cancer cell lines have been demonstrated, there is no report that demonstrates the difference in each subtype-induced antitumor activity in patients with RCC. Herein, we present a unique case of advanced RCC that is resistant to interleukin-2 and IFN-alpha administration, and we describe its response to another IFN-alpha administration. The difference between the two IFN-alpha types lies in the distribution of the subtypes: this case, therefore, suggests that the difference in the subtype distribution may cause the different response of the RCC. A 47 year-old male was diagnosed as left RCC with multiple lung metastases and underwent radical nephrectomy. The histological diagnosis was pT3b G2 clear cell carcinoma. He received intramuscular administration of 6 x 10(6) units of natural human IFN-alpha (Sumiferon) three times a week following the operation. However, the lung metastases showed progression. Thereafter, he received intravenous administration of 1.4 x 10(6) units of human interleukin-2 everyday. However, the lung metastases showed further progression and the hemoptysis, dyspnea, and chest pain deteriorated. Finally, he was given intramuscular administration of 5 x 10(6) units of another natural human IFN-alpha (OIF) three times a week. After the OIF administration, his complaints subsided and a chest CT scan revealed reduced lung metastases and diminished pleural effusion. He had not received any anti-tumor agents other than IFN-alpha or interleukin-2 since the operation. However, although he remained free of hemoptysis, dyspnea, and chest pain after OIF administration, the lung metastases increased again and multiple brain metastases were also observed five months after the first OIF administration. He died of metastatic RCC one year after the operation.

Antineoplastic Agents↗

PubMed2003

Prediction of extraprostatic cancer by prostate specific antigen density, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

BACKGROUND: The present study was designed to identify the preoperative parameters, including PSA-based parameters, and endorectal MRI, predictive of pathological stage in males who underwent radical prostatectomy. METHODS: We studied 114 patients who underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized prostate cancer. Clinical stage was assessed by DRE, pelvic CT scan, endorectal MRI, and bone scan. The correlation between the preoperative parameters, including PSA-based parameters, clinical stage, and histological findings of biopsy specimens, and the pathological stage was analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for local extent of disease. RESULTS: Seventy-six (66.6%) patients had organ confined cancer and 38 (33.4%) patients had extraprostatic cancer. Of the 38 patients with extraprostatic cancer, four had seminal vesicle involvement, while, none had pelvic lymph node involvement. Biopsy Gleason score, PSA, PSA-alpha1-antichymotrypsin (PSA-ACT), PSA-density (PSAD), PSA-transition zone density, PSA-ACT density, and PSA-ACT transition zone (TZ) density were significantly higher and percent free PSA was lower in the patients with organ confined cancer than those with extraprostatic cancer (P < 0.01). PSAD showed the largest area under the ROC curve (AUC) among those parameters (AUC = 0.732). Sixty-eight (74.7%) of 91 patients with T2 on endorectal MRI had organ confined cancer, while 15 (65.2%) of 23 patients with T3 had extraprostatic cancer (P < 0.01). Multivariate logistic regression analysis indicated that Gleason score (> or =7 vs. < or =6), endorectal MRI findings, and PSAD were significant predictors of extraprostatic cancer (P < 0.01). CONCLUSIONS: The present study demonstrated that preoperative PSAD was the most valuable predictor among PSA-based parameters for extraprostatic disease in patients with clinically localized prostate cancer. The combination of PSAD, endorectal MRI findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

Aged↗

PubMed2003

Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma.

Although an aggressive phenotype of renal cell carcinoma (RCC) is known to frequently be associated with inflammatory paraneoplastic syndrome including serum C-reactive protein (CRP) elevation, the molecular mechanism underlying this clinical phenomenon as well as what yields the malignant phenotype leading to the progression of RCC has yet to be elucidated. Based on the increased level of inflammatory cytokines such as interleukin-6 in advanced cases of RCC, a cytokine-inducible transcription factor, namely, nuclear factor-kappa B (NF-kappa B), may thus play a role in the progression of RCC. An electrophoretic mobility shift assay (EMSA) was carried out to determine the activity of NF-kappa B. Out of 45 cases of RCC, 15 cases (33%) showed a >200% increase in the NF-kappa B activity in comparison with that seen in normal renal tissue. In locally advanced cases (> or =pT3), 64% (9/14) showed an increased activity whereas it was only observed in 19% (6/31) of localized cases (< or =pT2). All three cases with metastases showed an increased NF-kappa B activity. The NF-kappa B activity determined by EMSA was further confirmed by an immunohistochemical analysis using an antibody recognizing the nuclear localization signal (NLS) in p65 subunit of NF-kappa B. The serum CRP elevation correlated with the increased NF-kappa B activation, and therefore NF-kappa B may be a causative transcription factor of inflammatory paraneoplastic syndrome. A high NF-kappa B activity was associated with an increased expression of both the p65 and p50 subunits of NF-kappa B and a concomitant decreased expression of I kappa B alpha. No functional mutations of the I kappa B alpha gene were detected. The NF-kappa B activity may therefore be a late event in carcinogenesis related to tumor development, thereby representing a possible molecular target in the treatment of RCC.

Adult↗

PubMed2003

Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma.

PURPOSE: Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed. RESULTS: Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5%) demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis. CONCLUSIONS: Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.

Adult↗

PubMed2003

Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma.

Positive inflammatory reactions in an aggressive phenotype are typical features of renal cell carcinoma (RCC). Although a high blood level of inflammatory cytokines, such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha, has been observed in these patients, the mechanisms underlying this clinical phenomenon remain to be elucidated. CCAAT/enhancer binding protein (C/EBP) family are transcription factors which play a role in cell differentiation and inflammatory reactions. Among these, C/EBP-beta induces a variety of cytokines and thus may play a role in the pathogenesis of RCC. We studied the activation of C/EBP-beta determined by electrophoretic mobility shift assay in nine RCC cell lines and 44 tissue samples. Six cell lines showed an activation of C/EBP-beta, whereas three cell lines did not, and two of these three had no expression at all of C/EBP-beta protein. Of 44 tissue samples, 12 (27.3%) showed a >200% increase in the activity compared with the corresponding normal kidney tissues. Locally advanced cases had a significantly higher rate of increased C/EBP-beta activity (5 of 8 = 62.5% in advanced cases versus 7 of 36 = 19.4% in localized cases). Especially, all four cases with renal vein invasion had an increased C/EBP-beta activity. These data suggest that the increased activation of C/EBP-beta may contribute to promote tumor invasiveness and render a malignant phenotype of RCC, although it needs to be validated in a larger series.

Adult↗

PubMed2002

STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P.

BACKGROUND: Although interleukin-6 (IL-6) has been suggested to function as an autocrine growth factor in renal cell carcinoma (RCC), the underlying mechanism responsible for the IL-6-induced proliferation of RCC has not been defined. The aim of this study was to characterize the signaling cascades mediating IL-6-induced proliferation and to investigate the use of effective novel interventions to block the IL-6-induced autocrine growth of renal cancer cells. METHODS: IL-6-induced proliferation and intracellular signaling cascades were analyzed in four human renal cancer cell lines Caki-1, ACHN, 769P and A498. IL-6-induced activation of STAT3 (signal transducer and activator of transcription-1) and extracellular signal-regulated kinases (ERKs), and the effects of anti-IL-6 neutralizing antibody, Jak inhibitor AG 490, and MEK1 inhibitor PD 98059 were analyzed by Western blotting using phospho-specific antibodies. The DNA-binding activities of STATs were analyzed by EMSA. Apoptosis was determined by using nuclear staining and the TUNEL assay. Changes in the apoptosis-related proteins, bcl-2, bcl-xL, and bax were analyzed by Western blotting. RESULTS: IL-6 induced tyrosine phosphorylation and increased the DNA binding activity of STAT3 and, to a lesser extent, STAT1 in all cell lines except for Caki-1, which did not express the IL-6 receptor subunit gp130. ERKs were constitutively activated in all cell lines and the activation level was not up-regulated further by exogenously added IL-6 nor down-regulated by anti-IL-6 neutralizing antibody. IL-6-induced STAT3 tyrosine phosphorylation and DNA binding activity was inhibited by treatment with Jak specific inhibitor AG 490; however, it was not affected by the MEK1 inhibitor PD 98059. Moreover, treatment with AG 490 inhibited IL-6-induced proliferation of ACHN and 769P cells and induced apoptosis with the down-regulation of bcl-2 and the up-regulation of bax. CONCLUSIONS: This study identified STAT3, but not ERKs, to be a major mediator of IL-6-induced proliferation of renal cancer cells. Although ERKs were constitutively activated, ERKs were not found to be essential for the IL-6-induced proliferation and modulation of the STAT3 activity. Because the Jak specific inhibitor AG 490 effectively inhibited the IL-6-induced STAT3 activity and induced apoptosis, the blockade of the STAT3 signaling pathways is considered to be potentially useful as a novel therapeutic approach for RCC.

Antibodies, Monoclonal↗

PubMed2002

[Perinephric liposarcoma mimicking cystic renal tumor].

Liposarcoma is one of the most common primary retroperitoneal neoplasms, and the perinephric region is a frequent location for them. Liposarcomas show a variety of radiographic features in terms of histological types and tumor sizes, so the specific diagnosis of liposarcoma is often difficult. We present a unique case of perinephric dedifferentiated liposarcoma mimicking cystic renal tumor. A 71-year-old man presented himself at our hospital with a palpable mass in his upper right abdomen. Abdominal computerized tomography (CT) revealed a well-defined cystic mass at the lower pole of the right kidney that contained heterogeneous solid components and small foci of fat. There were no signs of lymphadenopathy or tumor thrombus in the renal vein. Metastatic evaluation by chest x-ray and bone scan was negative. The probable diagnosis was cystic renal cell carcinoma or atypical angiomyolipoma. Because we could not exclude the possibility of cystic malignancy, a right radical nephrectomy was performed. Grossly, the tumor was predominantly encapsulated by a unilocular fibrous capsule and was filled with bloody fluid and debris. The anterior portion of the tumor was composed of various-sized soft and rubbery masses covered with necrotic tissue. The histological diagnosis was dedifferentiated liposarcoma arising in the perinephric retroperitoneum with extensive necrosis, and the cyst wall was composed of a necrotic tumor with a well differentiated liposarcoma and a fibrous capsule. Although the tumor widely covered the right kidney, there was no microscopic invasion of the kidney. No signs of tumor recurrence were noted six months after the operation.

Aged↗

PubMed2002

Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome.

PURPOSE: Signal transducer and activator of transcription 3 (STAT3) is known to have an important role in cytokine and growth factor signaling pathways. In various types of human malignant tumors STAT3 has been shown to be constitutively activated due to aberrant production of cytokines and growth factors. We examined the presence of STAT3 activation and its association with pathological features and clinical outcome in renal cell carcinoma cases. MATERIALS AND METHODS: We examined 48 paraffin embedded renal cell carcinoma specimens and corresponding nonneoplastic kidney tissues for the activation status of STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3 antibody, which recognizes only activated STAT3. Based on the percent of cells with positive nuclear staining the activation status of STAT3 was determined and categorized into 2 groups, including low-less than 10% and high-90% or more tumor cells positive. The associations of the activation status of STAT3 with pathological features and clinical outcome were analyzed. RESULTS: Of 48 tumors 24 (50%) demonstrated high levels of nuclear immunostaining for p-STAT3, while the other 24 (50%) showed low levels. Adjacent nonneoplastic kidney tissues showed only little immunostaining for p-STAT3. A significant association of high levels of p-STAT3 with metastasis was observed (p = 0.0094). No significant associations of p-STAT3 immunostaining with pathological stage or grade were observed. A high level of p-STAT3 was a significant indicator of a poor prognosis on univariate and multivariate analysis (p = 0.0117 and 0.0439, respectively) CONCLUSIONS: Our results indicate a high frequency of STAT3 activation in renal cell carcinoma, especially in metastatic disease. STAT3 activation was an independent prognostic variable in renal cell carcinoma cases. Our results strongly suggest that the activation of STAT3 contributes to the development and progression of renal cell carcinoma.

Acute-Phase Proteins↗