• Title/Summary/Keyword: Therapeutic flow

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Calnexin as a dual-role biomarker: antibody-based diagnosis and therapeutic targeting in lung cancer

  • Soyeon Lim;Youngeun Ha;Boram Lee;Junho Shin;Taiyoun Rhim
    • BMB Reports
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    • v.57 no.3
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    • pp.155-160
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    • 2024
  • Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.

Therapeutic effects of dihydroartemisinin and transferrin against glioblastoma

  • Kim, Suk Hee;Kang, Seong Hee;Kang, Bo Sun
    • Nutrition Research and Practice
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    • v.10 no.4
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    • pp.393-397
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    • 2016
  • BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

Development and Evaluation of the Herbal Medicine for Hair Growth-promoting Activity (발모 향상을 위한 한약재의 개발 및 효과 확인)

  • Choi, Sunkyung;Cho, Namjoon;Kim, Kee K.
    • KSBB Journal
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    • v.31 no.4
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    • pp.237-245
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    • 2016
  • Hair loss affects both men and women of all ages and often significantly affects social and psychologic health. Recent therapeutic approach for hair loss such as finasteride and minoxidil focused on regulation of hormonal system blood flow. However, long-term use of these drugs caused adverse effects. To develop herbal medicine for therapeutic effect on hair growth, here we screened the 10 medicinal herbs (Red ginseng, Licorice, Ulmus, Barberry root, Lycium root, Rehmanniae radix crudus, Sophora root, Sweet flag, Polygala root, Achyranthes) based on oriental medicine literature. We measured cytotoxicity, anti-oxidant activity, and $5-{\alpha}$ reductase inhibitory effect of the herbal medicine on human dermal papilla (DP) cells to investigate therapeutic effect of the herbal medicine. Treatment of the 1% herbal medicine did not show any cytotoxic effects, and cell growth was increased by treatment of the 0.1% herbal medicine. In addition, the herbal medicine showed stronger antioxidant activity than resveratrol and comparable inhibitory activity of $5-{\alpha}$ reductase with finasteride. Furthermore, when applied to in vivo mouse model, we also observed increases in the number and length of hair of the herbal medicine-treated group. These results suggest that the herbal medicine promotes hair growth by its antioxidant activity and inhibitory activity of $5-{\alpha}$ reductase and might therefore be a promising hair growth-promoting agent.

Review of the Neuroscientific Evidences for the People With Schizophrenia (조현병 환자의 신경과학적 근거에 대한 고찰)

  • Shin, Eun-Sik
    • Therapeutic Science for Rehabilitation
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    • v.2 no.1
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    • pp.5-12
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    • 2013
  • The purpose of this review is to address the flow of current neuroscientific researches and to provide for the clinicians with therapeutic evidences for schizophrenia which can help them clinical decision making. Since the very beginning, a lot of scientific studies about schizophrenia have been undertaken. In this review, I describes the evidences focused on development of schizophrenia including neurobiological dysfunction, neurodevelopmental model, Kalirin, and Brain-Derived Neurotrophic Factor(BDNF) and neuroanatomic abnormalities based on neuroimaging studies. In conclusion, schizophrenia influencing on broad impairment of human function such as activities of daily life, occupations, and relationships has been studied underlying causes and treatments, but still remained uncertainty. However, there are plenty of useful evidences available for the clinicians to make a good therapeutic choice.

Tumor-Infiltrating Neutrophils and Non-Classical Monocytes May Be Potential Therapeutic Targets for HER2negative Gastric Cancer

  • Juhee Jeong;Duk Ki Kim;Ji-Hyeon Park;Do Joong Park;Hyuk-Joon Lee;Han-Kwang Yang;Seong-Ho Kong;Keehoon Jung
    • IMMUNE NETWORK
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    • v.21 no.4
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    • pp.31.1-31.16
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    • 2021
  • Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45+ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2negative AGC.

Experimental Study of CheonghunHwadam-tang on the Cerebral Blood Flow in Rats (청훈화담탕이 국소뇌혈류량에 미치는 실험적 연구)

  • Kim Cheon Joong;Cho Su In;Jeong Hyun Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.2
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    • pp.316-321
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    • 2002
  • CheonghunHwadam-tang(CHT) have been used in oriental medicine for many centuries as a therapeutic agent of vertigo by wind, fire and phlegm. CheonghunHwadam-tangGamypang(CHTG) was CHT adding Aurantii Fructus(AF), Gastrodae Rhizoma(GR). The effects of CHT on the cerebral blood flow and cardiacvascular system is not known. The purpose of this Study was to investigate effects of CHT and CHTG on the regional cerebral blood flow(rCBF), mean arterial blood pressure(BP), cardiac muscle contractile force(CMF), heart rate(HR). The changes of cerebral blood flow and movement of cardiacvascular system(BP, CMF, HR) was determinated by Laser-Doppler Rowmetry(LDF). The results were as follows; 1. CHT extract increased rCBF, but decreased BP, HR in a dose-dependent manner. 2. AF extract accelerated rCBF and movement of cardiacvascular system in a dose-dependent manner. 3. GR extract increased significantly rCBF(10.0mg/kg, p<0.05) as well as accelerated BP and rCBF in a dose-dependent manner. 4. CHTG extract increased significantly rCBF(10.0mg/kg, p<0.01) in a dose-dependent, but was not changed movement of cardiacvascular system. This results suggest that CHTG is significantly treated more than CHT in vertigo by wind, fire and phlegm.

Effects of SosokMyeongTang extract on the Regional Cerebral Blood Flow and Blood Pressure in Rats (소속명탕(小續命湯)이 백서(白鼠)의 국소뇌혈류량(局所腦血流量)과 혈압(血壓)에 미치는 영향(影響))

  • Kim, Young-Kyun;Kwon, Jung-Nam;Kim, Kyung-Min;Cho, Eun-Hee;Park, Ji-Eun
    • The Journal of Internal Korean Medicine
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    • v.21 no.5
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    • pp.851-857
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    • 2000
  • SosokMyeongTang(SMT) have been used in oriental medicine for many centuries as a therapeutic agent for cerebral disease. The effects of SMT on the vascular system is not known. The purpose of this study was to investigate the effects of SMT on the changes in blood pressure(BP) and regional cerebral blood flow(rCBF) of rats. SMT consists of the following components : Radix Ledebouriellae(防風), Radix Cocculi or Stephaniae(防己), Semen Armeniacae(杏仁), Cortex Cinnamomi(肉桂), Radix Scutellariae(黃芩), Radix Paeoniae Lactiflorae(白芍藥), Radix Ginseng(人蔘), Rhizoma Cnidll(川芎), Herba Ephedrae(麻黃), Radix Glycyrrhizae(甘草), Radix Aconiti(附子?), Fructus Zizyphi Jujubae(大棗), Rhizoma Zingiberis(生薑) and the changes of BP and rCBF were tested Leser-Doppler Flowmetry(LDF) The experimental results were as follows ; BP was not affected by SMT in rats, but rCBF was increased significantly by SMT in a dose dependent manner. SMT increased previous decreasd rCBF due to pretreatment methylene blue, but did not increased previous decreasd rCBF due to pretreatment L-NNA, indomethacin. Pretreatment with indomethacin decreased BP compaired with control group. These results suggest that SMT causes a diverse response of blood pressure and regional cerebral blood flow(rCBF). The increased rCBF is mediated by nitric oxide synthease.

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Mechanism on the Changed-Regional Cerebral Blood Flow and Mean Arterial Blood Pressure by CheonghunHwadam-tang Adding Schiznepetae Herba in Rats (청훈화담탕가형개로 인해 변동된 국소뇌혈류량 및 평균혈압의 작용기전)

  • Min Byeng Il;Im Gwang Mo;Jeong Hyun Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.4
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    • pp.701-706
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    • 2002
  • CheonghunHwadam-tang(CHT) have been used in oriental medicine for many centuries as a therapeutic agent of vertigo by wind, fire and phlegm. CHTS was CHT adding Schizonepetae Herba. The effects of CHTS on the cerebral blood flow and blood pressure is not known. The purpose of this Study was to investigate effects of CHTS on the regional cerebral blood flow(rCBF) and mean arterial blood pressure(BP), action-mechanism of CHTS-induced changed-rCBF and BP. The changes of rCBF and BP was determinated by Laser-Doppler Flowmetry(LDF). The results were as follows ; CHTS extract was increased significantly rCBF in a dose-dependent, but was not changed BP compared with CHTS non-treated group. Pretreatment with propranolol, indomethacin and methylene blue were inhibited CHTS induced increase of rCBF, propranolol(all CHTS-treated group) and indomethacin(CHTS 0.01 mg/kg) of them were significantly decreased. Pretreatment with propranonol and indomethacin were inhibited CHTS induced increase of BP, but pretreated with methylene blue was significantly accelerated BP in high dosage. This results suggest that CHTS increased rCBF by dilating pial arterial diameter and the action of CHTS is also mediated by adrenergic β -receptor and cyclooxygenase.

Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide (Pentoxifylline과 Nicotinamide의 병용에 의한 생체내 방사선 감수성 증강 효과)

  • Lee Intae;Cho Moon-June
    • Radiation Oncology Journal
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    • v.9 no.1
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    • pp.7-15
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    • 1991
  • Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

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Validity and Reliability of a Korean Version of the Flow State Scale for Occupational Task (한글판 작업과제 몰입상태척도(Korean version of Flow State Scale for Occupational Task: K-FSSOT)의 타당도 및 신뢰도연구)

  • Lee, Jeong-Hoon;Park, Ji-Hyuk
    • Therapeutic Science for Rehabilitation
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    • v.10 no.4
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    • pp.53-63
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    • 2021
  • Objective : This study aimed to develop a Korean version of the Flow State Scale for Occupational Task (K-FSSOT), to measure the level of a flow experience of a subject in occupational therapy activities. Methods : To develop a measure of K-FSSOT, validity and reliability were verified through a systematic development process. The validity was verified by calculating the content validity index (CVI) through the content validity of 10 occupational therapists and a question-and-answer survey of 20 patients. Reliability was verified by investigating the internal consistency and examination-re-test reliability of 33 patients. Results : The item-CVI for each question in the content feasibility study was .90 to 1.00, and the scale-CVI, which is the average of the whole item, was found to be appropriate at .97. The verification of reliability indicated that the intrinsic value of the entire question was high at .855, and the test-retest reliability value was high at .894 (p<.01), showing a high correlation, and very high reliability. Conclusion : K-FSSOT could be used as a useful tool to measure the level of a flow experience of the target in performing occupational therapy activities for occupational therapists concerned about the participation and flow experience of the target.