• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1213-1217
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• 2015

Background: Gastric cancer is the second most common cause of cancer- related deaths worldwide and ranks $11^{th}$ or $14^{th}$ among all deaths. Patients with advanced disease require supportive care along with the medical and/or surgical treatment. Aim: To assess the need for palliative care for patients with advanced tumours along with standard clinical therapy. Materials and Methods: Eighty-four patients with metastatic (stage 4) gastric cancer, including both patients who had received surgical treatment or not, were followed up in Bagcilar Training and Research Hospital, Division of Medical Oncology between 2011 and 2014. They were categorised as supportive care (-) (Group 1, n=37) and (+) groups (Group 2, n=47) and evaluated retrospectively. Results: Demographic characteristics of the patients were as follows: mean age, Group 1, $65.2{\pm}10.5$ years, Group $2,63.7{\pm}11.3$ years; male/female ratio, Group 1, 21/16, Group 2, 28/19; distribution of Eastern Cooperative Oncology Group (ECOG) performance scores of 0 and 1, Group 1, ECOG 0 (n=9) and 1 (n=14), Group 2, ECOG 0 (34) and 1 (n=13) (p<0.0001); patients receiving second-line, Group 1 (n=7) and Group 2 (n=22) (p<0.008) or third - line chemotherapy,Group 2 (n=6) (p<0.02); mortality rates, Group 1, (n=28; 75.6%) and Group 2 (n=30; 63.8%); progression-free survival (PFS) rates, Group 1, $17.4{\pm}6$ weeks, Group 2, $28.3{\pm}16.2$ weeks; statistically significant overall survival rates, Group 1, $20.8{\pm}8.2$ weeks and Group 2, $28.3{\pm}162$ weeks (p<0.01). Conclusions: The supportive care team (medical oncologist, general surgeon, internal medicine specialist, algologist, psychiatrist and radiologist) can play a role in the treatment of metastatic gastric tumours, with improvements shown in terms of the performance status of cases, eligibility of patients to be on chemotherapy programmes for longer duration and overall survival rates in Turkey.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.339-346
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• 2000

Background : The moot important prognostic factor in non-small cell lung cancer is the TNM stage. Even after complete resection in early non-small cell lung cancer, the five-year survival rate is still low. However, new prognostic factors, including molecular biologic factors, have recently been found to guide the treatment of patients with non-small cell lung cancer. We evaluated the prognostic value of the loss of blood-group antigen A in tumor tissue, which has been implicated as an important prognostic factor for overall survival and the timing of the disease progression. Methods : The loss of blood-group antigen A was assessed immunohistochemically in paraffin-embedded tumor samples from 26 patients with blood types A or AB, who had undergone curative surgery. Monoclonal antibody was used to detect the blood group antigen A expression. Results : Fifteen patients (58%) expressed antigen A in their tumor tissue, whereas 11 patients (42%) did not show antigen A. The median survival time of the blood A antigen positive group was 11 months, while the median survival time of the blood A antigen negative group was 18 months. The difference in survival between the two groups was not statistically significant. Conclusion : The loss of blood-group antigen A in tumor tissue was not found to be a significant prognostic factor in patients with non-small cell lung cancer. This study needs to be extended for further evaluation.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.34-39
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• 2005

Purpose: KLF6, a member of the KLF family, is a ubiquitous zinc finger tumor suppressor protein that is mutated in several human cancers. Our aim was to determine whether the expression pattern of KLF6 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 85 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF6 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF6 protein was expressed on superficial and foveolar epithelial cells in the gastric mucosa. We found loss of KLF6 expression in 28 ($32.9\%$) of the 85 gastric cancer tissues. There was a significant correlation between loss of KLF6 expression and lymph-node metastasis. However, other pathologic parameters, such as histologic type, depth of invasion, and peritoneal dissemination, were not statistically associated with loss of KLF6 expression. Conclusion: Our findings suggest that loss of KLF6 expression may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development and/or progression of Korean gastric cancer.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.82-88
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• 2004

Purpose: E-cadherin and CD44H have been shown to play a role in the progression and the metastasis of tumors. This study evaluated the clinical correlations between expression of E-cadherin and CD44H and various clinicopathologic factors and the value of expressions of E-cadherin and CD44H as prognostic factors in Borrmann type IV gastric cancer. Materials and Methods: In 122 patients with Borrmann type IV gastric cancer, we performed the immunohistochemical stainings for E-cadherin and CD44H. We analyzed the correlation between the expressions of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, stage, and peritoneal dissemination, and survival. Results: There were no correlations between reduced expression of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, and stage. However, there was a significant correlation between lymph node metastasis and the lymphatic invasion (P=0.022). There was also a significant correlation between the peritoneal dissemination and CD44H expression (P=0.005). The 5-year survival rate was correlated with CD44H expression expression (P=0.026), peritoneal dissemination (P<0.01), depth of invasion (P<0.01), lymph node metastasis (P<0.01), stage of tumor (P<0.01), and lymphatic invasion (P<0.01). There was no correlation between expression of E-cadherin and survival rate. Conclusion: The expression of CD44H and peritoneal dissemination was correlated. The expression of CD44H was an independent prognostic factor in Borrmann type IV gastric cancer. Further prospective studies with a large number of cases are required.

• Journal of Life Science
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• v.26 no.6
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• pp.705-710
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• 2016

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related death worldwide. Although several diagnostic and therapeutic tools have been available, CRC remains difficult to complete cure because of insufficient understanding of the molecular mechanisms underlying this disease progression. MicroRNAs (miRNAs) are small non-coding RNA molecules that strongly regulate gene expression via transcriptional and translational control mechanisms. Many crucial cellular pathways are frequently disrupted in cancer development process due to dysregulation of several miRNAs. Mir-31 functions as an oncogene that modulate expression of multiple cancer related genes. Thus, we aimed to demonstrate clinical relevance of miR-31 in human CRC. Quantitative RT-PCR analysis of miR-31 expression was performed in 175 CRC tissues and 16 normal colonic mucosa (NM). Next, we investigated clinical significances of miR-31 expression in various clinicopathologic features in CRC patients cohort. Mir-31 was significantly up-regulated in CRC tissues compared to NM. In CRC tissues, miR-31 expression level was significantly elevated in a stage-dependent manner, which was associated with poor survival in patients with CRC. High miR-31 levels in CRC tissues significantly correlated with poor prognosis (hazard ratio [HR]=2.4) as well as distant metastasis (odds ratio [OR]=2.3). In conclusion, we identified clinical significance of miR-31 expression in CRC. High miR-31 expression may be clinically able to use as a biomarker for CRC prognosis and predicting metastasis.

• Molecules and Cells
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• v.38 no.2
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• pp.130-137
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• 2015

MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3'-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3'-UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.

• Journal of Korean Neurosurgical Society
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• v.67 no.5
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• pp.560-567
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• 2024

Objective : We investigated how treating large brain metastasis (LBM) using 2-day fraction Gamma Knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for 2 consecutive days, with a biologically effective dose equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods : Between November 2017 and December 2021, 42 patients (mean age, 68.3 years; range, 50-84 years; male, 29 [69.1%]; female, 13 [30.9%]) with 44 tumors underwent 2-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (n=16), small cell lung cancer (n=7), colorectal cancer (n=7), breast cancer (n=3), gastric cancer (n=2), and other cancers (n=7). Twenty-one patients (50.0%) had a single LBM, 19 (46.3%) had a single LBM and other metastases, and two had two (4.7%) large brain metastases. At the time of the 2-day fraction GKRS, the tumors had a mean volume of 23.1 mL (range, 12.5-67.4). On each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results : We obtained clinical and magnetic resonance imaging follow-up data for 34 patients (81%) with 35 tumors, who had undergone 2-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (p=0.019) and lung cancer origin (p=0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat stereotactic radiosurgery (SRS) ranged from 15-878 days (median, 263±38 days; mean, 174±43 days) after the 2-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion : Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.183-189
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. We investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the cell proliferation of human lung carcinoma A549 cells in order to understand its anti-proliferative mechanism. AEPG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. This anti-proliferative effect of A549 cells by AEPG treatment was associated with morphological changes such as membrane shrinking, cell rounding up and inhibition of cell migration. DNA flow cytometric histograms showed that populations of both Sand G2/M phase of the cell cycle were increased by AEPG treatment in a concentration-dependent manner. AEPG treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 and p27. In addition, SSS treatment resulted in down-regulation of Cdk2 and Cdk4 expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of S to G2/M phase progression the induction of apoptosis. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.39-44
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• 2015

Tolfenamic acid (TA) is a traditional non-steroid anti-inflammatory drug (NSAID) and has been broadly used for the treatment of migraines. Nuclear factor kappa B (NF-${\kappa}B$) is a sequence-specific transcription factor and plays a key role in the development and progression of inflammation and cancer. We performed the current study to investigate the underlying mechanisms by which TA suppresses inflammation focusing on NF-${\kappa}B$ pathway in TNF-${\alpha}$ stimulated human normal and cancer cell lines and lipopolysaccharide (LPS)-stimulated mouse macrophages. Different types of human cells (HCT116, HT-29 and HEK293) and mouse macrophages (RAW264.7) were pre-treated with different concentrations of TA and then exposed to inflammatory stimuli such as TNF-${\alpha}$ and LPS. Transcriptional activity of NF-${\kappa}B$, $l{\kappa}B-{\alpha}$-degradation, p65 translocation and mitogen-activated protein kinase (MAPK) activations were measured using luciferase assay and Western blots. Pre-treatment of TA repressed TNF-${\alpha}$- or LPS-stimulated NF-${\kappa}B$ transactivation in a dose-dependent manner. TA treatment reduced degradation of $l{\kappa}B-{\alpha}$ and subsequent translocation of p65 into nucleus. TA significantly down-regulated the phosphorylation of c-Jun N-terminal kinase (JNK). However, TA had no effect on NF-${\kappa}B$ signaling and JNK phosphorylation in HT-29 human colorectal cancer cells. TA possesses anti-inflammatory activities through suppression of JNK/NF-${\kappa}B$ pathway in different types of cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.255-260
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• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.