• Natural Product Sciences
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• 제26권4호
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• pp.311-316
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• 2020

The chemical investigation of the methanolic crude extract of leaves of Diospyros iturensis gave us 15 known secondary metabolites identified as mixture of α-amyrenone (1) and β-amyrenone (2), β-amyrin (3), mixture of β-sitosterol (4) and stigmasterol (5), betulin (6), uvaol (7), betulinic acid (8), ursolic acid (9), corosolic acid (10), actinidic acid (11),11-O-p-hydroxybenzoylbergenin (12), bergenin (13) and mixture of stigmasterol glucoside (14) and β-sitosterol glucoside (15) respectively. The structures of secondary metabolites were elucidated with the help of NMR and mass spectral data and by comparison of their spectral data with literature. Among the fifteen isolated compounds, four compounds were identified for the first time in Diospyros genus. These included uvaol (7), corosolic acid (10), actinidic acid (11) and 11-O-p-hydroxybenzoylbergenin (12). Crude methanolic extract of leaves and four isolated compounds including betulin (6), betulinic acid (8), 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) were evaluated for their antiproliferative activity against two cancer cell lines CAL-27 and NCI-H460 by the MTT assay, antioxidant potential and inhibitory activity against the lipoxygenase and urease enzymes, respectively. The results indicated that the methanolic crude extract of leaves exhibited moderate antioxidant activity and was inactive against the two cancer cell lines. Betulin (6), 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) exhibited moderate antioxidant and lipoxygenase inhibition with IC50 = 65.8, 85.6, 82.5 μM and IC50 = 58.5, 95.2, 76.2 μM, respectively. Furthermore, 11-O-p-hydroxybenzoylbergenin (12) and bergenin (13) exhibited moderate urease inhibition activity with IC50 values of 45.6 μM and 49.8 μM, respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5289-5296
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• 2015

Background: Despite the decreased incidence, gastric cancer is still a frequent cause of cancer related death. The 1st line 2 or 3 drugs regimen is still a debatable issue. HER2 targeted therapy has emerged as the standard of care, but it is unavailable in the Brazilian Public Health System. The end-point of this trial was overall survival (OS) in patients with metastatic gastric cancer treated in a public university hospital in Brazil. The secondary end-points were efficacy and safety of regimens with 2 (F+P) or 3 (EOX) drugs to develop an institutional guideline to facilitate optimal treatments. Materials and Methods: In this retrospective study, 1st line regimens were evaluated for OS and PFS stratified by age and ECOG using Cox regression. Results: 47 patients were treated over the last 3 years. In 1st line, 29 were treated with F+P (mean 59.3 years, 34.5% ECOG 2 and a mean of 5.69 cycles) and 16 with EOX (mean 47 years, 18.8% ECOG 2 and a mean of 5.44 cycles). The median OS was 13.8 months (95%CI 10.7-16.9). Response was evaluated in 40 cases and was 64.3% for EOX and 37.5% for F+P (p=0.25). The median PFS was 9.5 months for EOX and 5.6 months for F+P (HR 0.85, 95%CI 0.41-1.74). However, among patients with ECOG 2 mPFS was 3.70 vs 5.40 months, respectively (p=0.86). Regimens showed similar manageable adverse events. A total of 34 patients suffered progression and 14 received $2^{nd}$ line therapy. Diffuse histology (HR 1.89, 95%CI 1.22-2.88), achieving 2nd line (HR: 0.25, 95%CI 0.11-0.58) and treatment response (HR 0.23, 95%CI 0.12-0.47) were OS prognostic factors. Conclusions: Patients treated in our hospital had outcomes compatible with the literature. The regimen choice should be related to patient features. Second line treatment should be considered.

• Journal of Hospice and Palliative Care
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• 제14권4호
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• pp.197-203
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• 2011

목적: 암환자에게 통증은 가장 흔하고 영향이 큰 증상이다. 그러나 말기암환자에서 통증 강도에 대한 연구는 부족하였다. 본 연구는 중등도 이상의 통증과 연관된 요인을 밝히고자 한다. 방법: 우리나라 완화의료 기관 6곳의 입원 병동을 대상으로 말기 암 환자 162명 자료를 사용하였다. 통증은 담당의가 10점 만점 숫자통증등급으로 측정하였다. 중등도 이상의 통증은 보건복지부 지침의 정의에 따랐다. 증상 평가에는 MD Anderson 증상 평가조사지 한국어본을 활용하였다. 생존기간 예측은 입원 당시 담당 전문의가 하였다. 결과: 예측 생존 기간이 6주 미만인 경우와 지난 24시간 졸린 정도가 6점 이상인 경우가 중등도 이상의 통증과 유의하게 연관되었다(각각 P=0.012, P=0.046). 마약성 진통제 투여량도 중등도 이상의 통증에 비례하였다(P=0.004). 결론: 중등도 이상의 통증과 유의하게 연관된 요인은 예측 생존 기간이 6주 미만인 것과 상당한 졸림이었다. 이러한 요인을 나타내는 말기 암 환자에서 주의 깊은 통증의 감시와 적극적인 대비가 필요하다.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Journal of the Korean Wood Science and Technology
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• 제46권2호
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• pp.118-124
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• 2018

Juglans mandshurica is a fast growing hard species, which is a tree in family of Juglandaceae and has a wide distribution in China, Korea and eastern Russia. Plant materials from J. mandshurica have extensively been used in folk medicines to prevent or cure gastric, esophageal, lung and cardiac cancer. As one chain of our searching for anticomplementary agents from natural sources, two epimeric ellagitannins, [2,3-O-4,4',5,5',6,6',-hexahydroxydiphenoyl (HHDP))-(${\alpha},{\beta}$)-D-glucose] (I) and pedunculagin (II) were purified from 70% acetone extracts of the stem barks of J. mandshurica by Thin Layer Chromatography and Sephadex LH-20 column chromatography approaches. The chemical structures of the isolated compounds were characterized by MS, NMR, and a careful comparation with published literatures. The epimeric ellagitannins I and II exhibited inhibitory properties against a classical pathway of complementary system with 50 % inhibitory concentrations ($IC_{50}$) values of 65.3 and $47.7{\mu}M$, respectively, comparing with riliroside ($IC_{50}=104{\mu}M$) and rosmarinic acid ($IC_{50}=182{\mu}M$), which were used as positive controls. Thus, the work indicated both the two secondary metabolites possess excellent inhibitory activity and might be developed as potential anticomplementary chemicals.

• 대한정형도수물리치료학회지
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• 제22권2호
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• pp.35-39
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• 2016

Background: The superficial lymphatic system is divided into areas called lymphatic territories which are separated by watersheds. When the lymphatic system fails to remove its load either due to surgery, radiotherapy or some congenital malformation of it then the fluid and the proteins and wastes contained within it accumulates in that territory. Anastomotic connections exist across the watersheds and while they can work unaided manual lymph drainage (MLD) can significantly help drainage across them into unaffected lymphatic territories. The purpose of the study is to examine the effectiveness of a manual technique in moving fluids and softening hardened tissues using a tape measure and Patient-Specific Functional Scale. Methods: We examined the movement of fluids from the affected limbs of lymphedema patients who underwent a standardized 30-min treatment using the Dr. Vodder method of MLD. We chose a typical cross section of patients with secondary leg or secondary arm lymphedema. The lymphedema patient was also measured after the conclusion of treatment and underwent a follow-up control measurement, within 8 weeks. Both evaluation tools indicated a movement of fluid to different and unblocked lymphatic territories as well as a softening of tissues in some of the affected limbs. Results: MLD is an effective means of fluid clearance when it accumulates as a consequence of a failure of the lymphatic system. It seems likely that MLD has a systemic effect on the lymphatic system and that it can improve flow from otherwise normal tissues. Conclusions: It is hypothesized that a series of treatments would result in even more significant improvements.

• 한국임상약학회지
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• 제21권2호
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• pp.49-56
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• 2011

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7261-7264
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• 2013

Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

• The Korean Journal of Pain
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• 제29권1호
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• pp.53-56
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• 2016

Sacroiliac (SI) joint pain can result from degeneration, infection, malignancy, and trauma. Patients with metastatic bone pain who do not respond to conventional treatment may need more aggressive neuroinvasive approaches. Recently, pulsed radiofrequency (PRF) neuromodulation has emerged as a promising treatment alternative for refractory cases of SI joint pain. Nevertheless, there is no report on the treatment of pain arising from SI joint metastases with PRF. We are reporting about a 63-year-old woman suffering from buttock pain due to breast cancer metastases in the SI joint. We treated this patient with PRF neuromodulation of the L4-S3 primary dorsal rami and lateral branches using a rotating curved needle technique. The patient tolerated the procedures well, without any complications. She experienced about 70% reduction in pain, and pain relief was sustained for 10 months. This result suggests that PRF neuromodulation is a safe, effective treatment for pain from SI joint metastases.