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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-09-30)
    Abstract: Malignant brain tumors consist of malignancies originated primarily within the brain and the metastatic lesions disseminated from other organs. In spite of intensive studies, malignant brain tumors remain to be a medical challenge. Patient-derived organoid (PDO) can recapitulate the biological features of the primary tumor it was derived from and has emerged as a promising drug-screening model for precision therapy. Here we show a proof-of-concept based on early clinical study entailing the organoids derived from the surgically resected tumors of 26 patients with advanced malignant brain tumors enrolled during December 2020 to October 2021. The tumors included nine glioma patients, one malignant meningioma, one primary lymphoma patient, and 15 brain metastases. The primary tumor sites of the metastases included five from the lungs, three from the breasts, two from the ovaries, two from the colon, one from the testis, one of melanoma origin, and one of chondrosarcoma. Out of the 26 tissues, 13 (50%) organoids were successfully generated with a culture time of about 2 weeks. Among these patients, three were further pursued to have the organoids derived from their tumor tissues tested for the sensitivity to different therapeutic drugs in parallel to their clinical care. Our results showed that the therapeutic effects observed by the organoid models were consistent to the responses of these patients to their treatments. Our study suggests that PDO can recapitulate patient responses in the clinic with high potential of implementation in personalized medicine of malignant brain tumors.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2010
    In:  The American Journal of Chinese Medicine Vol. 38, No. 01 ( 2010-01), p. 51-64
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 38, No. 01 ( 2010-01), p. 51-64
    Abstract: Paeoniflorin, a component in Paeonia lactiflora Pall, inhibits nuclear factor-κB expression in chronic hypoperfusion rat and has anti-inflammatory properties. Therefore, the aim of the present study was to investigate the effect of paeoniflorin on cerebral infarct, and the involvement of anti-inflammation. We established an animal model of cerebral infarct by occluding both the common carotid arteries and the right middle cerebral artery for 90 min, followed by reperfusion of 24 hours. The ratios of cerebral infarction area to total brain area, and neuro-deficit score were used as an index to observe the effects of paeoniflorin on cerebral infarct. ED1 (mouse anti rat CD68), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), intercellular adhesion molecular-1 (ICAM-1), myeloperoxidase (MPO) immunostaining and apoptotic cells in the cerebral infarction region also were studied. The results indicated that both pre-treatment and post-treatment with paeoniflorin reduced the ratio of cerebral infarction area; pre-treatment with paeoniflorin also reduced the neurological deficit score. The counts of ED1, IL-1β, TNF-α, ICAM-1 of microvessels and MPO immunoreactive cells and apoptotic cells were increased in the cerebral infarction region; however, these increases were reduced by Paeoniflorin pre-treatment. In conclusion, Paeoniflorin reduced cerebral infarct and neurological deficit in ischemia-reperfusion injured rats, suggesting that paeoniflorin may have a similar effect in humans and might be a suitable treatment for stroke. Paeoniflorin reduced cerebral infarct, at least in part, involves the anti-inflammatory properties.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2010
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  • 3
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2000
    In:  The American Journal of Chinese Medicine Vol. 28, No. 02 ( 2000-01), p. 291-299
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 28, No. 02 ( 2000-01), p. 291-299
    Abstract: Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 μl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2000
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  • 4
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 1999
    In:  The American Journal of Chinese Medicine Vol. 27, No. 02 ( 1999-01), p. 257-264
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 27, No. 02 ( 1999-01), p. 257-264
    Abstract: This study investigated the anticonvulsant effect of Uncaria rhynchophylla (UR) and the physiological mechanisms of its action in rats. A total of 70 male Sprague-Dawley (SD) rats were selected for study. Thirty four of these rats were divided into 5 groups as follows: 1) Control group (n = 6): received intraperitoneal injection (i.p.) of kainic acid (KA, 12 mg/kg); 2) URl000 group (n = 10), 3) UR500 group (n = 6) 4) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 5) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Behavior and BEG were monitored from 15 min prior to drug administration to 3 hours after KA administration. The number of wet dog shakes were counted at 10 min intervals throughout the experimental course. The remaining 36 rats were used to measure the lipid peroxide level in the cerebral cortex one hour after KA administration. These rats were divided into 6 groups of 6 rats as follows: I) Normal group: no treatment was given; 2) Control group: received KA (12 mg/kg) i.p.; 3) UR l000 group, 4) UR500 group, 5) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 6) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Our results indicated that both UR 1000 and 500 mg/ kg decreased the incidence of KA-induced wet dog shakes, no similar effect was observed in the UR 250 mg/kg and carbamazepine 20 mg/kg group. Treatment with UR 1000 mg/kg, 500 mg/kg, or 250 mg/kg and carbamazepine 20 mg/kg decreased KA-induced lipid peroxide level in the cerebral cortex and was dose-dependent. These findings suggest that the anticonvulsant effect of UR possibly results from its suppressive effect on lipid peroxidation in the brain.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 1999
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  • 5
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2010
    In:  The American Journal of Chinese Medicine Vol. 38, No. 02 ( 2010-01), p. 251-263
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 38, No. 02 ( 2010-01), p. 251-263
    Abstract: Uncaria rhynchophylla (Miq) Jack (UR) is one of many Chinese herbs. Our previous studies have shown that UR has both anticonvulsive and free radical-scavenging activities in kainic acid (KA)-treated rats. The aim of the present study was to use the effect of UR on activated microglia, nitric oxide synthase, and apoptotic cells to investigate its function in neuroproction in KA-treated rats. UR of 1.0 or 0.5 g/kg was orally administered for 3 days (first day, second day, and 30 min prior to KA administration on the third day), or 10 mg/kg (intraperitoneal injection, i.p.) N-nitro-L-arginine methyl ester (L-NAME) 30 min prior to KA (2 μg/2 μl) was injected into the right hippocampus region of Sprague-Dawly rats. ED1 (mouse anti rat CD68), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) immunoreactive cells and apoptotic cells were observed in the hippocampus region. The results indicated that 1.0 g/kg, 0.5 g/kg of UR and 10 mg/kg of L-NAME reduced the counts of ED1, nNOS, iNOS immunoreactive cells and apoptotic cells in KA-treated rats. This study demonstrates that UR can reduce microglia activation, nNOS, iNOS and apoptosis, suggesting that UR plays a neuro-protective role against neuronal damage in KA-treated rats.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2010
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  • 6
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2001
    In:  The American Journal of Chinese Medicine Vol. 29, No. 02 ( 2001-01), p. 331-341
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 29, No. 02 ( 2001-01), p. 331-341
    Abstract: Gastrodia elata Bl. (GE) is a traditional Chinese herb that is commonly used in Chinese communities to treat convulsive disorders such as epilepsy. The purpose of the present study was to determine the anticonvulsive and free radical activities of GE in rats. In vitro studies were conducted by using brain tissue from 6 male Sprague-Dawley (SD) rats treated with 120 μg/ml of kainic acid (KA), with or without the addition of various concentrations of GE. In vivo studies were conducted in a total of 30 male SD rats divided into 5 groups of 6 rats which were treated as follows: 1) the normal group received an intraperitoneal injection (i.p.) of PBS (Phosphate buffer saline, 1 ml/kg); 2) the control group received KA (12 mg/kg) i.p.; 3) the GE 1.0 group received oral administration of GE 1.0 g/kg 30 min prior to KA administration; 4) the GE 0.5 group reveived oral administration of GE 0.5 g/kg 30 min prior to KA administration; 5) the PH group reveived oral administration of phenytoin 20 mg/kg 30 min prior to KA administration. Seizures were verified by behavioral observations, electroencephalograph (EEG) and electromyography (EMG). Lipid peroxide levels in the rat brain, luminol chemiluminescence (CL) and lucigenin-CL in the peripheral blood were measured simultaneously after behavioral observations. The results indicate that GE administration significantly reduced KA-induced lipid peroxide levels in vitro. Oral administration of GE 1.0 g/kg and phenytoin 20 mg/kg significantly reduced counts of wet dog shakes (WSS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats. In addition, oral administration of GE 1.0 g/kg significantly delayed the onset of WDS, from 30 min in the control group to 46 min in the 0.5 g/kg group, and 63 min in the GE 1.0 g/kg group. A significantly reduced level of lipid peroxides in the rat brain was found in the GE 1.0 g/kg, 0.5 g/kg, and phenytoin 20 mg/kg groups. The GE 1.0 g/kg group showed significant reduction of luminol-CL and lucigenin-CL counts in the peripheral blood compared to the control group. The results of the present study demonstrate that GE has anticonvulsive and free radical scavenging activities. Further studies are needed to determine the clinical effectiveness of GE as an anticonvulsant in humans.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2001
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  • 7
    In: Life Sciences, Elsevier BV, Vol. 65, No. 20 ( 1999-10), p. 2071-2082
    Type of Medium: Online Resource
    ISSN: 0024-3205
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1999
    detail.hit.zdb_id: 2013911-1
    SSG: 12
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  • 8
    In: Life Sciences, Elsevier BV, Vol. 67, No. 10 ( 2000-7), p. 1185-1195
    Type of Medium: Online Resource
    ISSN: 0024-3205
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2000
    detail.hit.zdb_id: 2013911-1
    SSG: 12
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  • 9
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 33, No. 04 ( 2005-01), p. 599-611
    Abstract: Our previous studies showed that Gastrodia elata (GE), an herb used in traditional Chinese medicine, has both anti-convulsive and free radical-scavenging activities in kainic acid (KA)-treated rats. The aim of the present study was to further investigate possible physiological mechanisms of GE against activities of neuronal nitric oxide synthase (nNOS) and microglia in KA-treated rats; 0.5 g/kg and 1.0 g/kg of GE extract were administered orally, whereas 20 mg/kg of N-nitro-L-arginine methyl ester (L-NAME) was administered intraperitoneally (ip), both at 30 minutes prior to KA (2 μg/2 μl) being injected into the right hippocampus region of rats. ED1-staining, apoptotic, inducible nitric oxide synthase (iNOS), and nNOS-staining cells were observed in the hippocampus region. The results indicated that 1.0 g/kg of GE and 20 mg/kg of L-NAME reduced the counts of ED1-stained cells, and 0.5 g/kg and 1.0 g/kg of GE, and 20 mg/kg of L-NAME reduced the numbers of apoptotic cells and nNOS-staining cells. In addition, 20 mg/kg of L-NAME also reduced the numbers of iNOS-staining cells, but 0.5 g/kg and 1.0 g/kg of GE did not. This study demonstrated that GE was able to reduce nNOS, microglia activation and apoptosis, suggesting that GE has a protective effect against neuronal damage in KA-treated rats.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2005
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  • 10
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2002
    In:  The American Journal of Chinese Medicine Vol. 30, No. 02n03 ( 2002-01), p. 369-378
    In: The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 30, No. 02n03 ( 2002-01), p. 369-378
    Abstract: Our previous studies have shown that the cerebral cortex modulates the physiological mechanisms of acupuncture. However, the role of the brain stem and spinal cord in acupuncture remains unclear. The present study investigated the action of the brain stem and spinal cord in acupuncture. A total of eight healthy adult volunteers were studied. Electrical stimulation of the supraorbital nerve in the supraorbital foramen was used to evoke the blink reflex. Electrical stimulation of the posterior tibial nerve in the right popliteal fossa was used to evoke the H reflex. Electroacupuncture (EA) of 2 Hz was applied to the Zusanli acupoint in the right or left leg. The area of the R1 and R2 components of the blink reflex, and the greatest H/M ratio and H-M interval of the H reflex were measured before EA, during EA and at various post-EA periods. These data were analyzed quantitatively by a computerized electromyographic examination system. The results indicate that EA did not change the R1 and ipsilateral R2 components of the blink reflex. EA depressed the contralateral R2 component of the blink reflex 10 minutes and 40 minutes after the start of EA, but not after 5 minutes. EA applied to the Zusanli acupoint did not change the H/M ratio or the H-M interval of the H reflex. The results of this study indicate that 2 Hz EA of the Zusanli acupoint does not change the R1 component of the blink reflex, and the H/M ratio and the H-M interval of the H reflex, suggesting that 2 Hz EA does not change the monosynaptic reflex in the brain stem and spinal cord in humans. We also found that EA at 2-Hz depressed the contralateral but not the ipsilateral R2 component of the blink reflex, suggesting that longer pathways, perhaps including the cerebral cortex, may play a role in the physiological mechanisms responsible for the effectiveness of acupuncture.
    Type of Medium: Online Resource
    ISSN: 0192-415X , 1793-6853
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2002
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