• Journal of Gastric Cancer
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• 제4권2호
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• pp.89-94
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• 2004

Purpose: There is no established treatment-related prognostic factor for gastric cancer except a curative tumor resection. This study was done to clarify the prognostic value of early postoperative intraperitoneal chemotherapy (EPIC) in patients with serosa-positive gastric cancer. Materials and Methods: We analyzed retrospectively the postoperative survival data of 209 patients with serosapositive gastric cancer treated by surgery and chemotherapy. The survival period for patients was calculated from the date of resection until cancer-related death or the last date of follow-up; Kaplan-Meier survival curves were plotted and compared by using the log-rank test. A multivariate analysis was done by using the Cox proportional hazards model. Results: Statistically significant differences in survival rates were noted based on gender, depth of invasion, lymph node metastasis, distant metastasis, stage, location of tumor, macroscopic type, extent of gastric resection, curability of surgery, and adjuvant chemotherapy. Five-year survival rates of patients who received EPIC and systemic chemotherapy were 49 per cent and 25 per cent, respectively (P=0.009). A multivariate analysis revealed that invasion of an adjacent organ, lymph node metastasis, total gastrectomy, and palliative surgery were poor independent prognostic factors. Also, EPIC had a marginal prognostic value (P=0.056). Conclusion: Perioperative intraperitoneal chemotherapy can possibly be one of the independent prognostic indicators in case of serosa-positive gastric cancer. (J Korean Gastric Cancer Assoc 2004;4:89-94)

• 대한한방내과학회지
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• 제30권1호
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• pp.36-50
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• 2009

Objectives : This study was aimed to verify the cytoprotective function, antioxidative effect and inflammation genes inhibitory effects of Lycium chinense Milie. Therefore the generation of superoxide anion radical ( $O_2\;^-$), peroxynitrite ($ONOO^-$), nitric oxide (NO) and prostaglandin $E_2$ $(PGE_2)$ was investigated in the renal epithelial cells of mouse. Effects of Lycium chinense Milie on the expression of inflammation-related proteins, $IKK-{\alpha}$. $p-IKK-\alpha\beta$, $p-I{\kappa}B-\alpha$, $NF-{\kappa}B$ (p50, p65), COX-2 and iNOS, were examined by western blotting. Methods : For this study, the fluorescent probes were used, namely dihydrorhodamine 123 (DHR 123), 4.5-diaminofluorescein (DAF-2) and 2',7'-dichlorodihydrofluorescein diacetate (DCFDA). Western blotting was performed using anti-$IKK-\alpha$, anti-phospho $IKK-\alpha\beta$, anti-phospho $I{\kappa}B-\alpha$, anti-$NF-{\kappa}B$ (p50, p65), anti-COX-2 and anti-iNOS, respectively. Results : Lyciutn chinense Milie reduced $H_{2}O_{2}$-induced cell death dose-dependently. It inhibited the generation of $O_2\;^-$, $ONOO^-$, NO and $PGE_2$ in the $H_{2}O_{2}$-treated renal epithelial cells of mouse in vitro. Lycium chinense Milie inhibited the expression of $IKK-\alpha$, $p-IKK-\alpha\beta,\;p-I{\kappa}B-\alpha$, COX-2 and iNOS genes by means of decreasing activation of $NF-{\kappa}B$. Conclusions : According to above results. Lycium chinense Milie recommended to be applied in treatment for the inflammatory process and inflammation-related diseases.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.213-220
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• 2022

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• Journal of Ginseng Research
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• 제47권4호
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• pp.493-505
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• 2023

In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related "ingredients-targets" network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5263-5272
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• 2012

Background: Gastric cancer (GC) is one of the most common cancers in China. Adjuvant chemotherapy (AC) is a routine auxiliary treatment for GC recommended by the guidelines issued in 2011 by the Ministry of Health of the People's Republic of China, but the relevant credible consequences in China have been insufficient because of China's late start and ethical concerns. Methods: A series of databases, including Cochrane Library, MEDLINE, EMBASE, the Chinese database of the National Knowledge Infrastructure and the VIP database, were searched by 2 reviewers independently for studies investigating AC for GC through March 2012. The retrieved literature was screened according to the eligibility criteria. Results: A total of 35 randomized control trials (RCTs) were subjected to the final analysis, including 4,043 patients in treatment group and 3,884 in the control group, as well as 4 clinical-control trials (CCTs), which accessed the final analysis with 238 and 252 patients, respectively. AC reduced the risk of death as a protective treatment with statistical significance (HR=0.91, 95%CI: [0.85, 0.97], P=0.002), and it seemed more effective for Asian than non-Asian patients. The effects of AC were not influenced by the starting time (P>0.05). D2 lymphadenectomy-based chemotherapy was effective (HR=0.89, 95%CI: [0.80, 0.99], P=0.04). Oral S-1 40 mg/m2 after D2 lymphadenectomy might be a better choice for Asians with advanced GC and might result in a greater reduction of adverse events than in non-Asian patients. GRADE quality assessment determined that the strength of the evidence from foreign studies from Europe, the United States and Asian countries other than China was high, while it was moderate for Chinese studies. Conclusion: AC was effective or even curative in Chinese patients in general, although it is still necessary to optimize a targeted AC scheme for Chinese patients with GC.

• Radiation Oncology Journal
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• 제14권1호
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• pp.33-39
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• 1996

목적 : 초기 자궁경부암은 수술과 방사선치료 모두 가능하며 결과도 비슷하다고 알려져있다. 이에 근치적 방사선치료를 받은 초기 자궁경부암 환자의 생존율, 실패율, 부작용등을 다른 결과와 비교하기 위하여 후향적 분석을 시행하였다. 대상 및 방법 : 근치적 방사선치료를 시행한 자궁경부암 IB 48명과 IIA 32명을 대상으로 하였다. 1985년 11월 부터 1993년 5월 까지 등록된 환자들로 최소 추적기간은 2년이었다. 외부전골반 방사선치료를 40-50Gy 시행후 3가지 다른 1회 조사량으로 고선량 강내치료를 시행후, 추적조사하여 생존율, 실패양상과 합병증등을 분석하였다. 결과 : 5년 생존율과 5년 무병 생존율은 각각 $72.3\%,\; 72.8\%$였으며 예후인자는 병기 병소의 크기, 병리조직 (선암), 방사선치료의 반응이었다. 19명의 치료실패가 있었으며 대부분 24개월이내에 발생하였다. Grade 2이상의 만성합병증은 방광이 $8.8\%$, 직장이 $15\%$, 모두 $17.5\%$ 였으며 발생율과 심한 정도는 강내치료 1회 조사량과 총 선량에 유의한 상관관계가 있었다. 결론 : 초기 자궁암의 방사선치료는 수술의 결과와 비슷하였으며 예후가 나쁜환자는 결과가 안좋아서 더 적극적인 치료방법이 필요하며 만성 합병증을 줄이기 위해서는 적절한 질 packing 등으로 주위조직의 방사선 피폭량을 줄이고 고선량 강내치료시 적절한 1회 조사량의 선택이 필요한 것으로 생각된다.

• Journal of Microbiology and Biotechnology
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• 제25권5호
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• pp.648-657
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• 2015

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

• 생명과학회지
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• 제32권3호
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• pp.210-221
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• 2022

비스테로이드소염제(NSAID)와 γ-secretase 저해제(DAPT) 또는 SIRT1저해제(MHY2245)의 병용 효과를 인간 대장암(KM12) 및 간암(SNU475) 세포를 대상으로 조사한 결과, celecoxib (CCB) 및 2, 5-dimethyl celecoxib (DMC)를 포함하는 NSAID는 DAPT 또는 MHY2245와의 병용에 의하여 COX-2활성과 상관없이 NSAID의 암세포 증식 억제능이 현저히 증강되었다. DAPT와 MHY2245는 p62단백질 감소와 동시에 Notch1, CD44, CD133, octamer- binding transcription factor 4 (Oct4) 등의 다수의 종양 줄기세포 표지자 및 NICD1 발현 양을 감소시켰지만, activating transcription factor 4 (ATF4) 발현은 증강시켰다. 또한 NSAID 단독처리 보다 NSAID/DAPT 및 NSAID/MHY2245 병용 처리에 의하여 오토파지가 촉진되므로서 종양 줄기세포 표지자의 발현 및 단백질양의 감소가 가속화되고, 이에 따라 PARP 활성화 및 세포사멸이 현저히 증강 되었다. 결론적으로 NSAID/DAPT 및 NSAID/MHY2245의 병용 투여는 종양 줄기세포 표지자를 발현하는 인간 암세포의 증식 억제 및 제거에 효과적인 처리방법으로, 임상에 적용시킬 수 있는 학문적 근거로서 제공 될 수 있다.