• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.86-87
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• 2015

Objectives: Condurango is widely used in various systems of complementary and alternative medicine (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats in vivo to validate its use as a traditional medicine. Methods: After one month of scheduled BaP feeding (50 mg/kg body-weight), lung cancer developed after four months. BaP-intoxicated rats were then treated with Condurango (0.06 mL) twice daily starting at the end of the four months for an additional one, two and three months, respectively. Effects of Condurango were evaluated by analyzing lung histology, reactive oxygen species (ROS) and antioxidant biomarkers, DNA-fragmentation, RT-PCR (Reverese Transcriptase-Polymerase Chain Reaction), ELISA (Enzyme linked immunosorbent assay) and western blot of several apoptotic signalling markers and comparing the results against those obtained for controls. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer-cell death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusions: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2757-2760
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• 2016

Gastric cancer (GC) is the fourth most prevalant cancer and the second leading cause of cancer-related mortality worldwide. As in other cancers gastric carcinogenesis is multifactorial involving environmental, genetic and epigenetic components. Epigenetic silencing due to hypermethylation of tumour suppressor genes is one of the key events in gastric carcinogenesis. This study was aimed to analyse the hypermethylation status of the E-Cadherin (CDH1) gene promoter in GCs in the ethnic Kashmiri population. In this study a total of 80 GC patients were recruited. Hypermethylation in tumour tissue was detected by methylation specific PCR (MS-PCR). Hypermethylation of CDH1 promoter was observed in 52 (65%) of gastric carcinoma cases which was significantly much higher than adjacent normal tissue [$p{\leq}0.0001$]. Further the frequency of CDH1 promoter methylation was significantly different with intestinal and diffuse types of gastric cancer [55.7% vs 82.1%; p<0.05]. Moreover females and cases with lymph node invasion had higher frequencies of CDH1 hypermethylation [$P{\leq}0.05$]. Thus the current data indicate a vital role of epigenetic alteration of CDH1 in the causation and development of gastric cancer, particularly of diffuse type, in our population.

• Journal of Life Science
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• v.22 no.12
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• pp.1621-1627
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• 2012

Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2004.11a
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• pp.126-129
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• 2004

We compared intensity-modulated radiotherapy (IMRT) treatment plans with commercially available multileaf collimators (MLCs) of different leaf width for intracranial lesions. Twelve cases previously treated with micro-MLCs(mMLCs) were replanned using the Varian 120 and 80 MLCs. These collimators have minimum leaf width of 3mm, 5 mm and 10 mm at isocenter, respectively. These three plans were compared with respect to the uniformity and the conformity indices, doses to normal tissue. For the uniformity index of planning target volume (PTV),there was no statistically significant difference between mMLCs with 120 MLCs (p = 0.06). However, there was a little difference between mMLCs with 80 MLCs (p = 0.001). Maximum target dose to the PTV showedno dependency with respect to the leaf width. On the contrary, there were statistically significant differences in the conformity indices between mMLCs and 120 MLCs (p = 0.003) and between mMLCs and 80 MLCs (p = 0.003).The volumetric increments for MLCs with leaf widths of 5 mm and 10 mm were 6.3% and 23.2% for the normal tissue Irradiated to = 50% dose, and 8.7% and 32.7% for the normal tissue Irradiated to = 70% dose, respectively, compared to the volume for MLCs with leaf width of 3 mm. This shows that for the sparing of normal tissue, MLCs with leaf width of 3 mm are more effective, compared to MLCs with leaf widths of 5 mm and 10 mm.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.180-185
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• 2005

Purpose: Among tumor-associated antigens, MAGE (melanoma antigen) was named as cancer/testis specific antigens because they are detected exclusively in the testis or cancer cells, including gastric carcinomas. Due to the elicitation of autoimmunitiy to tumors by these antigens either in vitro or in vivo and their tumor specificity, these antigens, thus, appear to be potential targets for tumor-specific immunotherapy. Materials and Methods: The fresh tumor tissue and normal gastric tissue samples were obtained from resected surgical specimens in 53 patients with gastric carcinomas. From the obtained cells, total cellular mRNA was extracted, and RT-PCR and nested PCR were run in 30 and 35 cycles respectively, with two different kinds of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results: In the 53 normal tissue, there was no expression of MAGE, but in the 53 cancer tissues, MAGE was expressed in 13 tissues (24.5%). Our data did not exhibit any correlation with the expression of the MAGE gene and clinicopathological factors. Conclusion: In our data, since 24.5% of gastric cancer tissues expressed MAGE, it should become possible to immunize a significant proportion of patients with advanced gastric carcinomas against the antigens encoded by these genes, provided that more antigenic peptides encoded by the genes of the MAGE family can be identified in the near future. (J Korean Gastric Cancer Assoc 2005;5:180-185)

• Journal of Life Science
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• v.21 no.5
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• pp.631-646
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• 2011

Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

• Progress in Medical Physics
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• v.15 no.3
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• pp.149-155
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• 2004

Purpose: To investigate the effects of tissue inhomogeneity corrections on the dose delivered to prostate cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT). Methods and Materials: For five prostate cancer patients, IMRT treatment plans were generated using 6 MV or 10 MV X-rays. In each plan, seven equally spaced ports of photon beams were directed to the isocenter, neglecting the tissue heterogeneity in the body. The dose at the isocenter, mean dose, maximum dose, minimum dose and volume that received more than 95% of the isocenter dose in the planning target volume ( $V_{p>95%}$) were measured. The maximum doses to the rectum and the bladder, and the volumes that received more than 50, 75 and 90% of the prescribed dose were measured. Treatment plans were then recomputed using tissue inhomogeneity correction maintaining the intensity profiles and monitor units of each port. The prescription point dose and other dosimetric parameters were remeasured. Results: The inhomogeneity correction reduced the prescription point dose by an average 4.9 and 4.0% with 6 and 10 MV X-rays, respectively. The average reductions of the $V_{p>95%}$ were 0.8 and 0.9% with the 6 and 10 MV X-rays, respectively. The mean doses in the PTV were reduced by an average of 4.2 and 3.4% with the 6 and 10 MV X-rays, respectively. The irradiated volume parameters in the rectum and bladder were less decreased; less than 2.1 % (1.2%) of the reduction in the rectum (bladder). The average reductions in the mean dose were 1.0 and 0.5% in the rectum and bladder, respectively. Conclusions: Neglect of tissue inhomogeneity in the IMRT treatment of prostate cancer gives rise to a notable overestimation of the dose delivered to the target, whereas the impact of tissue inhomogeneity correction to the surrounding critical organs is less significant.

• BMB Reports
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• v.34 no.1
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• pp.66-72
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• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.997-1000
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• 2015

Esophageal cancer represents the fourth most common gastrointestinal cancer and generally confers a poor prognosis. Prostaglandin-producing cyclo-oxygenase has been implicated in the pathogenesis of esophageal cancer growth. Here we report that prostaglandin dehydrogenase, the major enzyme responsible for prostaglandin degradation, is significantly reduced in expression in esophageal cancer in comparison to normal esophageal tissue. Reconstitution of PGDH expression in esophageal cancer cells suppresses cancer cell growth, at least in part through preventing cell proliferation and promoting cell apoptosis. The tumor suppressive role of PGDH applies equally to both squamous cell carcinoma and adenocarcinoma, which enriches our understanding of the pathogenesis of esophageal cancer and may provide an important therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6761-6763
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• 2015

Aims: To investigate the role of swelling anesthesia in repairing facial soft tissue defects after tumor resection and temporal superficial artery frontal branch of narrow pedicle flap. Materials and Methods: From January 2008 to June 2008, 16 patients from Department of Ophthalmology with eye or eyelid tumors after eyeball removal of eye and part resection of surrounding soft tissue, undergoing postoperative swelling anesthesia with superficial temporal artery flap repair to prevent facial soft tissue defect formation and bone exposure, were recruited. Results: In all 16 patients facial soft tissue defect repair had good effects, with limited bleeding, and short operation times. Seven days after surgery, all flaps were in good repair. On postoperative follow-up after 3 months, flaps showed a similar appearance as with facial tissue. Conclusions: Swelling anesthesia for superficial temporoparietal artery frontal branch of narrow pedicle flap to repair soft tissue defect after facial tumor resection is feasible, and is linked with good analgesic effects, high postoperative survival of skin flaps, and good cosmetic effects.