• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1993-1995
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• 2015

Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.

• Advances in nano research
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• 제12권6호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3045-3050
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• 2014

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.261-268
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• 2016

$Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

• 대한세포병리학회지
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• 제2권2호
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• pp.90-97
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• 1991

Liver is generally known as an organ which is most commonly involved by the metastic tumors. According to the tendency of using fine needle aspiration in the diagnosis of hepatic tumors, the differentital diagnosis between hepatocellular carcinoma and metastatic carcinoma frequently has been a main issue in the poorly differentitated cases, especially to the pathologists of Korea, an endemic area of hepatocellular carcinoma. Until now the problem has been usually solved by the comparison of cytologic characteristics of their tumor cells but not by background cytologic features which rarely have been studied. We observed the background cytologic features helpful for the differential diagnosis through the analysis of 20 cases who had confirmed primary cancer and were diagnosed as metastatic carcinomas in the liver by fine needle aspiration cytology. Twenty cases included 9 adenocarcinomas, 7 spuamous cell carcinomas, 1 small cell carcinoma, 1 carcinoid, 1 adenoid cystic carcinoma, and 1 renal cell cacinoma. Analysis of background cytologic features revealed that 77% of adenocacinoma cases showed benign mesenchymal components and hepatocytes and spuamous cell carcinoma cases disclosed benign mesenchymal tissue (71%) and necrosis (57%), Remaining cases showed variable combinations of benign mesenchymal component, necrosis, hepatocytes, and bile duct epithelial cells. No case revealed atypical hepatocytic naked nuclei, a useful cytologic finding of hepatocellular carcinoma. In summary, the background cytologic features more commonly observed in metastatic carcinomas than in the hepatocellular carcinoma were benign mesenchymal components, hepatocytes, necrosis, and bile duct epithelium. The endothelial cells and hepatocytic naked nuclei, two relatively specific findings of hepatocellular carcinoma were not observed except for renal ceil carcinoma. Above background cytologic features are thought to be helpful for the differential diagnosis between the hepatocellular carcinoma and various metastatic carcinomas in the poorly differentiated cases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1971-1976
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• 2015

Background: To evaluate our results in terms of response, survival and toxicity profile of sunitinib among Egyptian patients with metastatic renal cell carcinoma. Materials and Methods: Between January 2010 and December 2013, 44 patients with metastatic renal cell carcinoma who received sunitinib at an oncology center of Cairo university hospitals were enrolled in this retrospective analysis. Results: The median age of the patients was 53 years, 22 (50%) having localized disease at presentation, while the remaining half of the patients presented with metastasis. At a median follow up of 19 months, 9 (21%) patients achieved partial remission, while disease was reported stable in 20 cases (45%) and progressive in 7 (16%), 4 (9%) being lost to follow up, and 4 (9%) had discontinued therapy due to toxicity. The median overall survival was 23 months (95%CI 15.2 - 30.9), while progression free survival was 12 months (95%CI 11.6 - 12.3). The most commonly reported non hematological grade 3 adverse events included mucositis (15.9%), hand-foot syndrome (13.6%), and fatigue (9%), while the predominant grade 3 or 4 laboratory abnormalities were neutropenia (6.8%), followed by anemia in 4.5% of patients. Conclusions: Our efficacy data were comparable to the published literature in terms of progression free survival and overall survival, while toxicity profile is different from Asian and western countries. However, sunitinib adverse events were manageable and tolerable in most of our Egyptian patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4503-4506
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• 2016

Background: Lymph node and distant metastases are known as the prognostic factor in renal cell carcinoma (RCC). Clinical parameters are needed to predict metastases preoperatively. The aim of this study was to assess clinical predictive factors for lymph node and distant metastases. Materials and Methods: We collected RCC data from January 1995 until December 2015 at Cipto Mangunkusumo hospital in Jakarta. We only reviewed data that had renal cell carcinoma histopathology by operation or biopsy. Clinical information such as patient age, gender, hemoglobin (Hb), erythrocyte sedimentation rate (ESR), and tumor size (clinical T stage) were reviewed and analyzed by Chi-squre and logistic regression to establish clinical predictive value. Results: A total of 102 patients were reviewed. There were 32 (31.4%) with lymph node metastases and 27 (26.5%) with distant metastases. Age, Hb and clinical T staging were associated with nodal metastases. However, only Hb and clinical T staging were found to be associated with distant metastases. By logistic regression, we found T3-4 in clinical T-stage to be the only predictor of nodal metastases (OR 5.14; 1.87 - 14.09) and distant metastases (OR 3.42; 1.27 - .9.23). Conclusions: Clinical T-stages of T3 and T4 according to The AJCC TNM classification could be used as independent clinical predictive factors for lymph node or distant metastases in patients with RCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2253-2255
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• 2012

Objective: The objective of our present study was to assess the role of serum amyloid A (SAA) in stages and prognosis of renal cell carcinoma. Material and Methods: It was a hospital based retrospective study carried out in the Department of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January 2008 and $31^{st}$ December 2011. The variables collected were SAA, CRP. Approval for the study was obtained from the institutional research ethical committee. Quantitative analysis of human SAA and C-reactive protein (CRP) was performed by radial immune diffusion (RID) assay for all cases. Results: Of the 422 total cases of renal cell carcinoma, 218 patients had normal and 204 abnormal SAA. SAA levels were grossly elevated in T3 stage ($122.3{\pm}SD35.7$) when compared to the mean for the T2 stage ($84.2{\pm}SD24.4$) (p value: 0.0001). Similarly, SAA levels were grossly elevated in M1 stage ($190.0{\pm}SD12.7$) when compared to the M0 stage ($160.9{\pm}SD24.8$) (p: 0.0001). There was no significant association with elevated CRP levels ($209.1{\pm}SD22.7$, normal $199.0{\pm}SD19.5$). Conclusion: The validity of SAA in serum as being of independent prognostic significance in RCC was demonstrated with higher levels in advanced stage disease.

• The Korean Journal of Physiology and Pharmacology
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• 제7권2호
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• pp.111-117
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• 2003

Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum(II) coordination complexes (PC-1 & PC-2) containing trans-${\iota}$ and cis-1,2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum(II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.34-40
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• 2019

Transglutaminase 2 (TGase 2) plays a key role in p53 regulation, depleting p53 tumor suppressor through autophagy in renal cell carcinoma. We found that microtubule-associated protein 1A/1B-light chain 3 (LC3), a hallmark of autophagy, were tightly associated with the level of TGase 2 in cancer cells. TGase 2 overexpression increased LC3 levels, and TGase 2 knockdown decreased LC3 levels in cancer cells. Transcript abundance of LC3 was inversely correlated with level of wild type p53. TGase 2 knockdown using siRNA, or TGase 2 inhibition using GK921 significantly reduced autophagy through reduction of LC3 transcription, which was followed by restoration of p53 levels in cancer cells. TGase 2 overexpression promoted the autophagy process by LC3 induction, which was correlated with p53 depletion in cancer cells. Rapamycin-resistant cancer cells also showed higher expression of LC3 compared to the rapamycin-sensitive cancer cells, which was tightly correlated with TGase 2 levels. TGase 2 knockdown or TGase 2 inhibition sensitized rapamycin-resistant cancer cells to drug treatment. In summary, TGase 2 induces drug resistance by potentiating autophagy through LC3 induction via p53 regulation in cancer.