• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5687-5690
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• 2015

Background: Factors predictive of survival have been identified in Western patients with metastatic clear cell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictive of survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients with mCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46 consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemical markers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniand multivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associated with poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International Metastatic RCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations (p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorer PFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in response to sunitinib was significantly higher in patients with normal (${\leq}0.5mg/dl$) than elevated baseline CRP (p<0.001). Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treated with first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response to sunitinib treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.867-872
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• 2012

Background: $FOXP3^+$ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. Design: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect $FOXP3^+$ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. Results: The presence of $FOXP3^+$ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between $FOXP3^+$ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between $FOXP3^+$ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. Conclusions: In this study, a positive correlation between the presence of $FOXP3^+$ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3161-3166
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• 2016

Background: Metastatic renal cell carcinoma (mRCC) status as poor prognosis improved with the introduction of tyrosine-kinase inhibitors, especially sunitinib. There is sparse data reporting from our region on use of sunitinib in metastatic RCC. Thus the present study explores sunitinib usage at our institute. Materials and Methods: An unselected population of patients with metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. Results: Fourty-nine patients with a median age of 50.5 years (range 21-71 years) were included. Most were male (61.2%). Twenty‑one (42.9%) had metastatic disease at presentation. Sunitinib was first line therapy in 45. Conventional clear cell carcinoma was the most common pathology present (39 patients; 79.59 %). The most common site of metastasis was the lung (75.5%). Most patients (30) were started at a dose of 50 mg once a day for 4 weeks and then 2 weeks rest. Clinical benefit rate was 73.5% (n= 36), and 22.5% (n= 11) demonstrated progressive disease at first imaging evaluation within the first 3-6 months. The following objective response performed for patients was 48.9% (n=24) and progression at 24.5 % (n=12). The median follow‑up was 16 months (range, 4-34 months), the overall estimated median PFS was 9 months and the estimated median OS was 15 months. Conclusions: This study demonstrated sunitinib is tolerable and effective in advanced/metastatic RCC Egyptian patients and indicates we should further seek second and third lines to increase survival equivalence as reported in the worldwide literature.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.82-89
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• 2006

Background: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix, which is an important step in tumor invasion and metastasis. A positive correlation between the expression of MMP-9 and aggressive behavior of renal cell carcinomas (RCCs) has been reported. MMP-9 expression in RCCs and adjacent normal kidney tissues were examined in this study. Materials and Methods: Twenty-five patients pathologically diagnosed as clear cell RCCs, from specimens obtained at radical nephrectomy, between May 2003 and December 2004 were enrolled in this study. MMP-9 activity was estimated using gelatin zymography, and quantified using a laser densitometer. The results were compared with clinicopathological characteristics. Results: The expression of MMP-9 was significantly elevated in the RCC compared with non-tumor kidney specimens (p<0.01). The levels of MMP-9 expression in the RCC patients with large tumors (>4 cm) or vascular invasion were significantly higher than in those without these clinical manifestations (p<0.01). There were also significant differences in the expression of MMP-9 among T stages (p<0.01). The tissue MMP-9 level was the highest in nuclear grade 4, but there was no statistical significance between the histological grades (p=0.17). Conclusions: These results suggest that enhanced MMP-9 expression contributes to carcinogenesis and tumor progression in the later stages of RCC.

• The Korean Journal of Urological Oncology
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• v.16 no.3
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• pp.89-96
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• 2018

Upper tract urothelial carcinoma (UTUC) has a relatively low prevalence rate of about 1.8 per 100,000 people. According to the recent literature, the development of diagnostic techniques has gradually increased the prevalence and diagnosis rate. In the past, when UTUC was diagnosed, more than 60% of the patients were diagnosed as locally advanced or metastatic cancer. However, since 2010, approximately 70% of the patients have been diagnosed as operable stage. Although radical nephroureterectomy is known as the basis of treatment for UTUC, overall survival is poor in patients with lymph node invasion. Especially, the finding that a localized UTUC is associated with a high risk of cancer metastasis in approximately 50% of patients suggests that these patients may not have sufficient treatment through surgery alone. The European Association of Urology and the National Comprehensive Cancer Network guideline 2017 suggested that postoperative adjuvant chemotherapy may be considered in patients with advanced UTUC beyond pT2. Also, recent meta-analyses have reported that cisplatin-based adjuvant chemotherapy can be expected to have a synergistic effect of overall survival and disease-free survival. However, many patients with UTUC undergo postoperative renal failure, which may result in failure to perform cisplatin-based adjuvant chemotherapy with adequate dose. For this reason, several researchers have suggested that it is beneficial to apply neoadjuvant chemotherapy when the preoperative renal function is maintained to a certain extent. But, neoadjuvant chemotherapy has not been used by many clinicians because of the lack of studies and the rarity of the disease. We are currently discussing the outcomes and prospects of perioperative chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3901-3905
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• 2015

Objective: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. Materials and Methods: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. Results: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). Conclusions: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.386-389
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• 2001

An endobronchial metastasis is defined as a subsegmental or a more proximal central bronchial metastasis of a nonpulmonary neoplasm in the bronchoscopically visible range. However, the frequencies of endobronchial metastasis range from 2 to 50% of pulmonary metastases from extrathoracic neoplasms by a different definition of an endobronchial metastasis. Primary neoplasms of an endobronchial metastasis including breast cancer, colon cancer, renal cell carcinoma, and ovarian cancer are relatively common. However, an endobronchial metastasis arising from thyroid cancer, parotid gland tumor, bone tumor, bladder cancer, and stomach cancer has only rarely been reported in the literature. Here we report a case of an endobrochial metastases from a hepatocellular carcinoma.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.2
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• pp.197-202
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• 2013

The objective of this study is to evaluate the anti-cancer and anti-inflammatory activities of plum (Formosa, Oishiwase, Soldam) for the future development of functional food products. To determine the anti-inflammatory effect of different types of plums, the inhibitory effect of plum extracts on nitric oxide (NO) production were measured in lipopolysaccharide (LPS)-stimulated Raw 264.7 mouse macrophage cells and human cancer cell lines (A549, Ags, Hela, Hep3B). Among the three different plum cultivars, Oishiwase at a concentration of 1 mg/mL showed the highest inhibitory effects on NO production (%) in Raw 264.7 macrophage cells. Moreover, Oishiwase exhibited a higher anti-cancer activity against A549 (renal carcinoma, 50%), Ags (gastric carcinoma, 35%), HeLa (cervical carcinoma, 50%), and Hep3B (hepatocellular carcinoma, 31%) at a concentration on 1 mg/mL, respectively, compared to Formosa and Soldam. Our findings suggest Oishiwase plum extracts may serve as potential dietary sources of natural health promoting substances.

• International Journal of Oral Biology
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• v.42 no.2
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• pp.79-83
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• 2017

Abnormal HLA-G expression occurs in various diseases such as melanoma, renal cell carcinoma, asthma, and classic Hodgkin's lymphoma. The purpose of this study was to determine whether HLA-G gene is linked with oral squamous cell carcinoma (OSCC). To investigate the possible link with susceptibility to OSCC, 54 OSCC patients and 120 healthy controls were enrolled in this study. HLA-G 14bp insertion/deletion polymorphism is in 3'-untranslated region of HLA-G gene. HLA-G 14bp insertion/deletion polymorphism was analyzed using the polymerase chain reaction (PCR) method. For the analysis of genetic data, SPSS18.0 program was used. Logistic regression models were performed for odds ratio (OR), 95 percent confidence interval (CI), and P value. There was a significant difference in distribution allele between OSCC patients and control subjects (OR=0.018, 95% CI=0.002-0.131, p<0.001). Our results suggest that HLA-G 14bp insertion/deletion polymorphism may be linked with susceptibility to OSCC in the Korean population.

• Advances in nano research
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• v.12 no.6
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.