• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.61-70
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• 2004

Heptaplatin is a new platinum derivative with antitumor activity against gastric cancer. Preclinical studies showed that it is less toxic than other platinum analogues. The purpose of this study is to evaluate the efficacy and toxicity of the combination therapy of heptaplatin and 5-fluorouracil in Korean advanced gastric cancer patients. This study was investigated retrospectively. The patients group consisted of 65 advanced gastric cancer patients with no prior radiotherapy. All patients received heptaplatin $400\;mg/m^2$ by 2-3 hour infusion on Day 1 and 5-FU $1000\;mg/m^2by 12-24 hour continuous infusion for 5 days. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. As results, objective response occurred in 16 patients $(24.6\%)$. Two were complete and 14 were partial response. Median progression free survival was 32 weeks with $29\%$ of patients progression free at 1 year. The most common hematologic toxicity was anemia. Grade 3 or 4 anemia was seen at $2.7\%$ of treatment cycles. Grade 3 or higher leucopenia was seen at $1.2\%$ of cycles. Grade 3 or 4 neutropenia and thrombocytopenia occurred at $6.1\%\;and\;1.5\%$ of cycles, respectively. The most common nonhematologic toxicity was proteinuria. Though no patients experienced grade 3 or 4 proteinuria, proteinuria was a considerable factor for this chemotherapy. Grade 3 or higher gastrointestinal toxicities were nausea and vomiting ($4.6\%$ of patients) and diarrhea ($1.5\%$ of patients). Grade 2 renal toxicity with elevation of serum creatinine was seen in $0.3\%$ of cycles, which is less than that of other platinum analogues. This study showed that combination therapy of heptaplatin and 5-FU have modest antitumor activity against advanced gastric cancer without severe renal toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6681-6686
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• 2013

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

• The Korean Journal of Cytopathology
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• v.2 no.2
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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.

• Childhood Kidney Diseases
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• v.24 no.2
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• pp.75-82
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• 2020

Objectives: We aimed to investigate the incidence, manifestations, and outcomes of malignancy after pediatric kidney transplantation (KT) at our center over 30 years. Methods: We retrospectively reviewed the medical records of 155 patients under 18 years of age who underwent KT between January 1990 and February 2020 at Asan Medical Center. Results: Twelve patients (7.7%) were diagnosed with a malignancy after KT. Malignancy was diagnosed after a mean period of 6.4±5.9 years (median 4.6, range 0.5-20.6 years) after KT. Nine (75.0%) of the 12 cancer patients were diagnosed with post-transplant lymphoproliferative disease (PTLD), and the other three had papillary thyroid cancer, mucoepidermoid cancer of the hard palate, and T-cell acute lymphoblastic leukemia, respectively. PTLD was diagnosed within a mean of 3.7±3.4 years (median 3.7, range 0.5-9.8 years) after KT. Five patients diagnosed with PTLD were cured without recurrence. Three patients with PTLD died from the disease, and one patient with mucoepidermoid cancer from a non-PTLD malignancy died after progression, despite surgical resection and chemotherapy. Three (33.3%) of the nine survivors progressed to end-stage renal disease (ESRD) after completing cancer treatment. No patient with post-transplant malignancy (PTM) experienced critical renal deterioration during cancer treatment. Conclusion: PTLD was the most common PTM, occurring at 5.8% of the pediatric KT patients after KT in our center. Careful follow up is needed particularly considering the risk of PTLD after KT in children.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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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.

• Journal of Life Science
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• v.26 no.5
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• pp.614-619
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• 2016

The prostate-apoptosis-response-gene-4 (Par-4) protein has been identified as an effector of cell death in response to various apoptotic stimuli in prostate cancer cells. We found that overexpression of Par-4 by stable transfection inhibits cell migration and invasion in Caki cells. The expression of various matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we investigated whether ectopic expression of Par-4 modulates MMP-2 expression and activity in human renal carcinoma Caki cells. We found that overexpression of Par-4 markedly inhibited MMP-2 activity, but not MMP-9 activity. However, loss of the leucine zipper domain of Par-4 (Par-4 ΔLZ#1 and #2) did not inhibit MMP-2 activity. Further, knock-down of Par-4 with the corresponding siRNA resulted in increased invasion and metastasis of renal carcinoma Caki cells. Interestingly, overexpression or knock-down of Par-4 did not affect the expression levels of MMP-2 mRNA. Taken together, our findings suggest that Par-4 may inhibit MMP-2 activity through its post-transcriptional regulation in renal carcinoma Caki cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6637-6641
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• 2013

Background: To evaluate the results of various types of radiofrequency ablation (RFA) treatment of renal tumors in patients with excessive anesthetic and surgical risk. Materials and Methods: Data for RFA performed in in high risk patients were retrospectively evaluated. Other RFA applications in patients with no anesthetic and/or surgical risk were excluded. RFA was by ultrasound or CT guided percutaneous (USG/CT-PRFA) and retroperitoneally or transperitoneally laparoscopic (R/T-LRFA) techniques under general or local anethesia. Follow-up data of enhanced CT or MRI after 1, 3 and 6 months were analysed for twelve RFA applications. Results: The RFA applications included 4 (40%) left-sided, 5 (50%) right-sided and 1 (10%) bilaterally RFA (simultaneously 1 right and 2 left). The localizations of tumors were 2 (16.6%) upper, 5 (41.6%) mid and 5 (41.6%) lower pole. The RFA applications included 9 (75%) USG-PRFA, 1 (8.3%) CT-PRFA, 1 (8.3%) T-LRFA and 1 (8.3%) R-LRFA. The mean age was $65.3{\pm}8.5$ (52-76) years. The mean tumor size was $29.6{\pm}6.08$ (15-40) mm. No complications related to the RFA were encountered in any of the cases. Failure (residual tumour) was determined in 8.3% (1/12) of USG-RFA application. The success rate was thus 91.7% (11/12). Other 1st, 3rd and 6th months follow-up data revealed no residua and recurrence. Conclusions: RFA application appears to be safe as a less invasive and effective treatment modality in selected cases of small renal tumors in individuals with excessive anesthetic and also surgical risk.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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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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• v.15 no.8
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• pp.3789-3795
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• 2014

This study aimed to analyze the expression, clinical significance of filamin A (FLNA) in renal cell carcinoma (RCC) and biological effects in a cell line by regulating FLNA expression. Immunohistochemistry and Western blotting were used to analyze FLNA protein expression in 70 cases of RCC and normal tissues to study the relationship with clinical factors. FLNA lentiviral and empty vectors were transfected into RCC to study the influence of up-regulated expression of FLNA. FLNA siRNA was transiently transfected into ACHN kidney carcinoma cells by a liposome-mediated method and protein was detected by Western blotting. The level of expression was found to be significantly lower in RCC than normal tissues (p<0.05). No correlation was noted with gender, age, tumor size or pathological types (p>0.05), but links with lymph node metastasis, clinic stage and histological grade were noted (p<0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (p<0.05). Results for biological function showed that ACHN cells transfected with FLNA had a lower survival fraction, significant decrease in migration and invasion, higher cell apoptosis, higher percentage of the G0/G1 phases, and lower MMP-9 protein expression compared with ACHN cells untransfected with FLNA (p<0.05). However, renal 786-0 cells transfected with FLNA siRNA had a higher survival fraction, significant increase in migration and invasion, and higher MMP-9 protein expression compared (p<0.05). In conclusion, FLNA expression was decreased in RCC and correlated significantly with lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that FLNA may play important roles as a a tumor suppressor in RCC by promoting degradation of MMP-9.