• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.5
• /
• pp.2383-2388
• /
• 2016

Background: The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene linked to several malignancies. Objective: To analyze any association between RECK gene rs10814325 single-nucleotide polymorphism (SNP) and HCC susceptibility with various clinicopathological and laboratory data. Materials and Methods: RECK gene rs10814325 SNP was estimated, using real-time PCR, in 30 HCC patients on top of HCV infection, 30 HCV related cirrhotic patients and 30 healthy controls. Results: No special pattern of association could be detected on comparing the RECK gene rs10814325 genotypes(P=0.5), or alleles(P=0.49) among the studied groups. HCC patients with TT genotype had younger age (mean of $54.1{\pm}6.0$ years vs $60.6{\pm}10.2$ years for TC/CC genotypes, P=0.035). Abdominal distension was significantly greater in TT genotype patients (75% vs 30%for TC/CC genotypes, P=0.045). The TT genotype was present in 75% of patients with lymph node metastasis. Serum GGT levels were higher in TT genotype patients [80 (48.5-134.8) IU/L vs 40 (33-87.5) IU/L for TC/CCgenotypes], and lower limb edema was observed in 60% for TT vs 20% for TC/CCgenotypes, but both just failed to reach significance (p=0.05 and p=0.06 respectively). Conclusions: RECK gene rs10814325 T>C could not be considered a risk factor for HCC development on top of HCV, but may be related to the disease progression and metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.5
• /
• pp.2435-2438
• /
• 2016

Background: MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Materials and Methods: Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Results: The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. Conclusions: The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.10
• /
• pp.4583-4586
• /
• 2016

Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma, with a pathognomonic chromosomal translocation t (11;14). Prognosis is uniformly dismal but there is a paucity of information on MCL from India. Materials and methods: We retrospectively analysed clinicopathological information on all treated patients with MCL at our centre. STATA 14.0 was used for analysis. Survival was assessed by Kaplan-Meier analysis and the Cox's proportional hazards method. Statistical significance was defined as a P value of < 0.05. Results: Fifty-one patients with MCL were reviewed. The median age at presentation was 57.0 years. Extranodal involvement was seen in 39.0 (74.0%) while bone marrow positivity at presentation was found in 27.0 (54.0%). Initial treatment was chemotherapy with or without rituximab. Patients receiving rituximab-based therapy (n = 24) had 5-year progression-free survival (PFS) of 21.0 (88.0%), compared with 14.0 (61.0%) for those not receiving rituximab (n = 23, P = 0.036). Twenty-three patients were alive with a median follow-up of 20.7 months (range 2.5-89.2). PFS at 1 and 2 years was 51.0% and 27.0%, and overall survival (OS) 78.0% and 72.0%, respectively. Use of more than 2.0 lines of therapy, use of bendamustine-rituximab, and high TLC (>10,000.0/cu.mm) significantly affected PFS. Conclusions: In our experience, MCL patients from north India have an early age at presentation. When treated with regimens including rituximab results in an improved response rate and PFS. This study provided comprehensive insights into the treatment of MCL in a developing country.

• Journal of Yeungnam Medical Science
• /
• v.33 no.2
• /
• pp.166-169
• /
• 2016

Afferent loop obstruction following gastrectomy is a rare but fatal complication. Clinical features of afferent loop obstruction are mainly gastrointestinal symptoms. A 56-year-old female underwent radical total gastrectomy with Roux-en-Y esophagojejunostomy for treatment of advanced gastric cancer. After fourteen months postoperatively, she showed gradual development of edema of both legs. Computed tomography (CT) scan showed disease progression at the jejunojejunostomy site and consequent dilated afferent loop, which resulted in inferior vena cava (IVC) compression. A drainage catheter was placed percutaneously into the afferent loop through the intrahepatic duct and an IVC filter was placed at the suprarenal IVC, and self-expanding metal stents were inserted into bilateral common iliac veins. With these procedures, sympotms related with afferent loop obstruction and deep vein thrombosis were improved dramatically. The follow-up abdominal CT scan was taken 3 weeks later and revealed the completely decompressed afferent loop and improved IVC patency. Surgical treatment should be considered as the first choice for afferent loop obstruction; however, because it is more immediate and less invasive, non-surgical modalities, such as percutaneous catheter drainage or stent placement, can be effective alternatives for inoperable cases or risky patients who have severe medical comorbidities.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2003.10a
• /
• pp.107-107
• /
• 2003

The activation of protooncogenes or the inactivation of their gene products may be a specific and effective functional study for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the HccR-2 protooncogene in vivo. The new human cervical cancer protooncogene (HccR-2) was detected from cervical cancer cell line. To elucidate its biological functions, we generated transgenic mice that expressed the HccR-2 gene. The sustained expression of the HccR-2 transgene culminated chronic neutrophilic leukemia (CNL). CNL is a rare chronic myeloproliferative disorder that presents as a sustained, mature neutrophilic leukocytosis with few or no circulating immature granulocytes, the absence of peripheral blood monocytosis, basophilia, or eosinophilia, and infiltration of neutrophils at the liver, spleen and kidney. Mice expressing the HccR-2 and tetracycline-transactivating protein (tTa) transgene were found to have altered myeloid development that was characterized by increased percentages of mature neutrophil and band form neutrophil in the peripheral blood, liver and spleen. Activation of the transgene causes CNL. In our model, expression of HccR-2 transgene mice was similar in many respects to the human CNL. This model will be valuable not only for investigating the biological properties of the HccR-2 and other protooncogenes in vivo but also for analyzing the mechanism involved in the progression of CNL.

• BMB Reports
• /
• v.32 no.2
• /
• pp.112-118
• /
• 1999

The presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment such as in radiation therapy or treatment with some anticancer drugs. It has been suggested that hypoxic cells are involved in the development of a more aggressive phenotype and contribute to metastasis. In this study, as an attempt to understand how tumor cells adapt to hypoxic stress, we investigated the regulation of the hypoxia-induced expression of proteins that control essential processes of tumor cell survival and angiogenesis. We first examined whether hypoxia induces stress protein gene expression of murine solid tumor RIF cells. We also examined hypoxia-induced changes in angiogenic gene expression in these cells. Finally, we investigated the association of the elevated levels of stress proteins with the regulation of hypoxia-induced angiogenic gene expression. Results demonstrated that hypoxia induced the expression of the erythropoietin (EPO) gene and at least two major members of stress proteins, heat shock protein 70 (HSP70) and 25 (HSP25) in RIF tumor cells. Evidence that the expression of EPO gene was greatly potentiated in TR cells suggested that the elevated levels of HSPs may play an important role in the regulation of the hypoxia-induced EPO gene expression. One of the RIF variant cell lines, TR, displays elevated levels of HSPs constitutively. Taken together, our results suggest that a hypoxic tumor microenvironment may promote the survival and malignant progression of the tumor cells by temporarily increasing the level of stress proteins and expressing angiogenic genes. We suspect that stress proteins may be associated with the increase of the angiogenic potential of tumor cells under hypoxia.

• Development and Reproduction
• /
• v.16 no.4
• /
• pp.363-370
• /
• 2012

The outer dense fiber 2 (ODF2) protein is an important component of sperm tail outer dense fiber and localizes at the centrosome. It has been reported that the RO072 ES cell derived homozygote knock out of ODF2 results in an embryonic lethal phenotype, and XL169 ES cell derived heterozygote knock out causes severe defects in sperm tail development. The ODF2s splicing variant, Cenexin1, possesses a C-terminal extension, and the phosphorylation of serine 796 residue in an extended C-terminal is responsible for Plk1 binding. Cenexin1 assembles ninein and causes ciliogenesis in early stages of the cell cycle in a Plk1-independent manner. Alternatively, in the late stages of the cell cycle, G2/M phase, Cenexin1 binds to Plk1 and results in proper mitotic progression. In this study, to identify the in vivo function of Plk1 binding to phosphorylated Cenexin1 S796 residue, and to understand the in vivo functional differences between ODF2 and Cenexin1, we generated ODF2/Cenexin1 S796A/Cenexin1 WT expressing transgenic mice in a RO072 ES cell derived $ODF2^{+/-}$ knock out background. We observed a severe defect of sperm tail development by ectopic expression of Cenexin1 S796A mutant and no phenotypic differences between the ectopic expression of ODF2/Cenexin1 WT in $ODF2^{+/-}$ background and in normal wild type mice.

• Journal of Korean Neurosurgical Society
• /
• v.58 no.3
• /
• pp.205-210
• /
• 2015

Objective : This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. Methods : We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. Results : Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. Conclusions : Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2681-2685
• /
• 2012

Objectives: This study focused on PTEN and Livin expression and associations with malignancy in human renal clear cell carcinomas (RCCC). Methods: PTEN and Livin expression was assessed in 100 RCCC tissue samples, 50 paracarcinoma cases, and 20 normal renal tissue samples using the immunohistochemical Streptavidin proxidase (SP) method. The relationships between binding and corresponding biological characteristics, such as histological grade, lymph node metastases, and clinical stages were analyzed. Results: Positive PTEN expression in RCCC was significantly lower than in renal tissue adjacent to carcinoma tissue and normal renal tissue (P<0.01). Livin expression in the renal tissue adjacent to the carcinoma and normal renal tissues exhibited only low levels, whereas overall Livin expression in RCCC was statistically significant (P<0.01). In RCCC, PTEN expression rate gradually decreased with an increase in clinical stage, whereas that of Livin increased to statistically significant levels (P<0.01), PTEN and Livin levels being negatively correlated (r=-0.395, P<0.01). Conclusions: PTEN and Livin are important in RCCC development. The two factors combined are expected to provide indices for estimating RCCC malignancy and progression levels, as well as references for RCCC diagnosis and treatment.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2467-2471
• /
• 2012

Introduction: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes. Methods & Materials: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 & D15 and either etoposide $100mg/m^2$ IV D1-D5 and cisplatin $20mg/m^2$ IV D1-D5 (5 day BEP regimen) or etoposide $165mg/m^2$ D1-D3 and cisplatin $50mg/m^2$ D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed. Results: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites. Conclusion: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.