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Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy

  • Yin, Mei;Kim, Yeo-Ok;Choi, Jeong-Il;Jeong, Seongtae;Yang, Si-Ho;Bae, Hong-Beom;Yoon, Myung-Ha
    • The Korean Journal of Pain
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    • v.33 no.4
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    • pp.318-325
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    • 2020
  • Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

  • Ma, Ji-wei;Zhang, Yong;Ye, Ji-cheng;Li, Ru;Wen, Yu-Lin;Huang, Jian-xian;Zhong, Xue-yun
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.186-193
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    • 2017
  • Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

  • Mollazade, Mahdie;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Zarghami, Nosratollah;Nasiri, Marzieh;Jahanban-Esfahlan, Rana;Alibakhshi, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6925-6928
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    • 2013
  • Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the $IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.

Effect of Hormone Therapy on Long-term Outcomes of Patients with Human Epidermal Growth Factor Receptor 2-and Hormone Receptor-Positive Metastatic Breast Cancer: Real World Experience in China

  • Du, Feng;Yuan, Peng;Wang, Jia-Yu;Ma, Fei;Fan, Ying;Luo, Yang;Xu, Bing-He
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.903-907
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    • 2015
  • Background: Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer, more than half are also hormone receptor (HR)-positive. Although HR is a predictive factor for the efficacy of hormone therapy, there are still some uncertainties in regard to the effects on patients with HR-positive and HER2-positive metastatic breast cancers due to the potential resistance to hormone therapy caused by co-expression of HR and HER2. There are no clinical trials directly comparing the efficacy of hormonal therapy with chemotherapy. Materials and Methods: To examine the real-world effect of hormone therapy on patients with HR-positive and HER2-positive metastatic breast cancers, a cross-sectional study of a representative sample of the Chinese population was conducted. The study included 113 patients who received first-line and second-line palliative treatment between 2005 and 2010 in the Cancer Institute and Hospital, Chinese Academy of Medical Science. The effect of hormone therapy on overall survival (OS) was studied. Results: The patients who received hormone therapy (n=51) had better overall survival in contrast to those who received chemotherapy with anti-HER2 therapy (n=62) in first- or second-line treatment. The difference was of borderline statistical significance (51.8m vs 31.9m, p=0.065). In addition, the effect of hormone therapy did not differ significantly with other prognostic factors, including age (${\leq}50$ years or >50 years), disease free survival (${\geq}2$ years or < 2 years) and site of metastasis (visceral or bone/soft tissue). On multivariate analysis, administration of hormone therapy was associated with a trend toward a favorable prognosis (p=0.148, HR=0.693, 95%CI 0.422-1.139). Age more than 50 years was the sole independent harmful prognostic factor (p<0.001, HR=2.797, 95%CI 1.676-4.668). Conclusions: Our data suggest that hormonel therapy may improve outcomes of the patients with ER-positive and HER2-positive metastatic breast cancer.

Protective Effect of Acanthopanax senticosus Extract on Alloxan-induced β-cell Damage

  • Rho, Hye-Won;Lee, Ji-Hyun;Kim, Jong-Suk;Kim, Hyung-Rho;Park, Byung-Hyun;Park, Jin-Woo
    • Preventive Nutrition and Food Science
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    • v.10 no.1
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    • pp.46-51
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    • 2005
  • The protective effect of Acanthopanax senticosus (AS) extract on alloxan-induced pancreatic β-cell damage was investigated in HIT T-15 cells, a Syrian hamster pancreatic β-cell line. Alloxan caused the pancreatic β-cell damage through the generation of reactive oxygen free radicals, increased DNA fragmentation, and decreased cellular NAD/sup +/ levels. The β-cell damage was significantly prevented by the pretreatment with water soluble extract of AS roots. These results suggest that the protective effect of AS extract, on alloxan-induced β-cell damage, is primarily due to the inhibition of the generation of reactive oxygen free radical species (ROS) by alloxan.

Studies on the Efficacy of Combined Preparation of Crude Drug (XXIV) -Effect on Diuretic, Antipyretic, Anti-inflammatory and Analgesic Actions of Shirhyung-Tang and Kamishirhyung-Tang- (생약(生藥) 복합제제(複合製劑)의 약효(藥效) 연구(硏究)(제24보)(第24報) -시령탕(柴笭湯) 및 가미시령탕(加味柴笭湯)의 이뇨(利尿), 해열(解熱), 소염(疏髥) 및 진통작용(鎭痛作用)에 대(對)하여-)

  • Hong, Nam-Doo;Kim, Jong-Woo;Doo, Ho-Kyung;Cho, Young-Whan;Hwang, Hwa-Soo
    • Korean Journal of Pharmacognosy
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    • v.16 no.4
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    • pp.191-198
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    • 1985
  • The investigation was aimed to study effects of Shirhyung-tang extract and Kamishirhyung-tang extract on the diuretic, antipyretic, anti-inflammatory, analgesic and the injured kidney induced by $HgCl_2$. The extract was administered to the experimental animals. The following results have been obtained. Duiretic effect was noted to be significant in extracts of Shirhyung-tang and Kamishirhyung-tang. Antipyretic effect was noted to be significant according to the density of Shirhyung-tang and Kamishirhyung-tang. Anti-inflammatory effect was noted to be significant in extract of Shirhyung-tang and Kamishirhyung-tang. Analgesic effect was noted to be significant in extracts of Shirhyung-tang and Kamishirhyung-tang.

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Study on Study on Antitumor Activity of Kamisamchulsamja-tang (가미삼출삼자탕의 항암활성에 관한 연구)

  • Kim Seong Eon;Lee Hyo Jeong;Kim Dong Hee;Song Gyu Yong;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.4
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    • pp.667-673
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    • 2002
  • The purpose of this study was to investigate the effect of Kamisamchulsamja-tang (KSST) water extract on the antitumor activity. The results were summarized as follows: KSST extract exhibited a weak cytotoxicity against HT1080, A549, SK-OV-3, B16-F10 and SK-MEL-2 cells. KSST extract showed a inhibitoty effect on DNA topoisomerase I from calf thymus in a dose-dependent manner. Also, KSST extract showed antiadhesive effect on HT1080 cells but didn't showed on A549 cells to complex extracellular matrix. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in KSST treated group as compared with control group. In vitro neovascularization assays, angiogenesis was significantly inhibited in KSST treated group than control group. In CAM assay, KSST extract inhibited angiogenesis significantly at 15㎍/egg concentration as compared with control. From the above results it was concluded that KSST showed antitumor effect through the antimetastatic effect. So it is expected to be clinically helpful on the prevention of metastasis of cancer.

Protective Effect of Puerariae Radix on Ovariectomy-induced Bone Loss in Rats

  • Park, Jeong-A;Lee, Sung-Ok;Moon, Eun-Jung;Kim, May;Lim, Seong-Cheol;Cho, Min-Hyoung;Kim, Sun-Yeou
    • Natural Product Sciences
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    • v.17 no.3
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    • pp.189-197
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    • 2011
  • To examine the bone-protective effects of Puerariae Radix (PR) in an estrogen-deficient animal model, we treated ovariectomized rats with PR at a dose of 10.0 mg/kg 3 times a week for 16 weeks. Our results showed that PR increased mineral content and density of the trabecular bone at the neck of the left femur. Moreover, biochemical data indicated that PR had a positive effect on bone turnover. No endometrial hyperplasia was detected in the PR group. The present data suggest that PR should be considered for use in the treatment of bone loss in women with postmenopausal osteoporosis.