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Biomedical subjects

B S Teh

Publications and source records attributed to B S Teh.

27 records · Page 2Linked to original sources

Inhibition of prostaglandin and leukotriene generation by the plant alkaloids tetrandrine and berbamine.

We compared the effects of two bisbenzylisoquinoline compounds on leukotriene and prostaglandin generation by human monocytes and neutrophils. The results show that tetrandrine had a much greater effect than berbamine on leukotriene generation. However, both compounds were equally potent in suppression of prostaglandin generation. This inhibitory effect on prostaglandin generation can be overcome by exogenous arachidonic acid (AA), suggesting that the site of inhibition is not on the cyclooxygenase enzyme complex, but more proximally on the phospholipase-mediated release of AA from the cell membrane, similar to the action of corticosteroids. These results, together with previous findings of inhibitory effects on other inflammatory mediators such as histamine, platelet-activating-factor (PAF) and interleukin 1 (IL-1) indicate that these plant alkaloids may be useful lead compounds for the development of a new class of anti-inflammatory drugs.

Alkaloids↗

Effects of the plant flavonoid baohuoside-1 on cancer cells in vitro.

The novel plant flavonoid 3,5,7,-trihydroxy-4'-methoxyl-8'-prenylflavone-3-O-alpha-L-rham nopranoxide (designated baohuoside-1) was shown to have cytotoxic and cytostatic effects on 6 cancer cell-lines, by means of microscopy, 51Cr-release and growth inhibition. The IC50 on the cells tested ranged from 2.8 to 7.5 micrograms/ml. At tumouricidal concentrations, inhibition of DNA and RNA synthesis, but not protein synthesis was observed.

Animals↗

Anti-inflammatory and immunosuppressive properties of the bis-benzylisoquinolines: in vitro comparisons of tetrandrine and berbamine.

Tetrandrine and berbamine are two naturally occurring analogues with a bis-benzylisoquinoline structure. Comparative in vitro studies show that tetrandrine has significantly greater suppressive effects on adherence, locomotion and 3H-deoxyglucose uptake of neutrophils, as well as the mitogen-induced lymphocyte responses and mixed lymphocyte reactions. Also, tetrandrine displayed anti-oxidant activity while berbamine did not. By contrast, berbamine demonstrated a significantly greater capacity for inhibition of NK cell cytotoxicity. These results show that tetrandrine is superior to berbamine in most aspects of anti-inflammatory and immunosuppressive activity. Since these two alkaloids differ by only one substitution in the side chain of one of the benzene rings, these findings may provide further insight into structure-activity relationships and clues to the synthesis and development of active analogues of this promising class of drugs for the treatment of chronic inflammatory diseases.

Alkaloids↗

Suppression by tetrandrine of human platelet aggregation induced by platelet-activating factor and other stimulants.

Tetrandrine was found to have inhibitory effects on platelet-activating factor induced platelet aggregation in a dose-dependent manner. There was preferential inhibition of platelet aggregation induced by agents such as collagen, thrombin, adrenaline, and adenosine diphosphate. No inhibitory effect of tetrandrine was observed on platelet aggregation induced by adenosine diphosphate, arachidonic acid, and the calcium ionophore A23187. These results support our previous findings of interference with the phosphatidylinositol second-messenger system as one of the sites of action of tetrandrine. Since platelets may have an important role in the pathogenesis of asthma and other allergic diseases, these findings suggest that tetrandrine may have clinical application as a non-steroidal broad-spectrum anti-allergic drug.

Adenosine Diphosphate↗

Effect of tetrandrine on immunological responses and cardiac transplant rejection in mice.

Mice treated with the plant alkaloid tetrandrine have a reduced capacity to mount delayed-type hypersensitivity (DTH) responses. This suppressive effect on DTH was more pronounced when treatment was begun 2 days prior to immunization with sheep erythrocytes. Similar dosage regimens significantly delayed the rejection of cardiac transplants. By contrast, there was significant enhancement of antibody production. These immunomodulatory properties of tetrandrine may account for some of its potential in the treatment of chronic inflammatory diseases, where immunological mechanisms are known to play a major role in pathogenesis.

Alkaloids↗

Inhibition of histamine release from rat mast cells by the plant alkaloid tetrandrine.

The plant alkaloid tetrandrine was shown to have significant inhibitory effects on receptor-ligand-mediated histamine release from rat mast cells at concentrations similar to or lower than that observed with theophylline and sodium cromoglycate. Inhibition of histamine release did not occur when non-specific stimulants such as aspirin, A23187 or adenosine triphosphate were used. Inhibition of ovalbumin-IgE and concanavalin A-mediated histamine release was reversible by washing the cells, showing that tetrandrine does not bind tightly to the cell membrane or cytoplasmic components. These results, taken together with previous reports of its anti-phagocytic, anti-oxidant and immunosuppressive properties, suggest that tetrandrine may be a broad spectrum non-steroidal drug of potential value in the treatment of allergic diseases.

Alkaloids↗

The Baylor College of Medicine experience with gold seed implantation.

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.

Adult↗

The potential use of intensity modulated radiotherapy (IMRT) in women with pectus excavatum desiring breast-conserving therapy.

The purpose of this study was to determine if intensity modulated radiation therapy (IMRT) offers a better treatment plan compared to conventional radiotherapy for patients with pectus excavatum desiring breast-conserving therapy and to assess the feasibility of simultaneous modulated accelerated radiation therapy (SMART) boost. A patient with pectus excavatum desired breast-conserving therapy for her early stage breast cancer. She underwent lumpectomy and axillary lymph node dissection followed by chemotherapy. She was then referred for radiotherapy. A breast board (Med-Tec) with aquaplast body cast was used to limit the movement of the patient, chest wall, and breasts before planning a computed tomography (CT) scan. IMRT including dose-volume histogram (DVH) was compared to that of the conventional plan using parallel opposed tangential beams with a 15-degree wedge pair. Forty-five gray was prescribed to the whole breast to each plan, while 50 Gy was prescribed to the tumor bed using IMRT with SMART boost in 25 fractions over 5 weeks. The coverage of the whole breast was adequate for both plans. IMRT allowed a more homogeneous dose distribution within the breast at the desired dose range. With IMRT there is less volume of ipsilateral lung receiving the radiation dose that is above the tolerance threshold of 15 Gy when compared to that of the conventional plan. However, there is more volume of surrounding normal tissues (the heart, spinal cord, and contralateral breast and lung) receiving low-dose irradiation when IMRT was employed. SMART boost was feasible, allowing a mean dose of 57 Gy to be delivered to the tumor bed simultaneously along with the rest of the breast in 5 weeks. IMRT is feasible in treating early breast cancer patients with pectus excavatum by decreasing the ipsilateral lung volume receiving high-dose radiation when compared to the conventional method. SMART boost shortens the overall treatment time that may have potential radiobiological benefit.

Adult↗

Concurrent chemotherapy and "concomitant boost" radiotherapy for unresectable head and neck cancer.

PURPOSE: For patients with advanced head and neck cancer, various combined chemoradiotherapy regimens have been used to improve local control. This study was carried out to assess the outcome of concomitant chemotherapy with a "concomitant boost" radiotherapy in the treatment of advanced unresectable head and neck cancer patients. MATERIALS AND METHODS: Forty-eight patients were treated with combined chemoradiotherapy between the years of 1990 and 1995. Cisplatinum (100 mg/m2) was given intravenously during week 1 and week 5. A "concomitant boost" external beam radiotherapy approach was used with twice-daily treatment delivered during the last 2 weeks. A total of 70 Gy was delivered over 6 weeks. Median follow-up was 23.5 months (2-79 months). RESULTS: Thirty-one (65%) and 17 (35%) patients achieved complete and partial response, respectively. Median survival in complete responders has not been reached. Overall survival at 2 years, 3 years, and 5 years were 58.7%, 52.8%, and 42.4%, respectively. Median overall survival was 38.8 months. Acute confluent mucositis (Radiation Therapy Oncology [RTOG] grade 3) developed in 50% of patients, but there was no severe long-term treatment-related toxicity. CONCLUSION: This combined chemoradiotherapy approach is safe and efficacious for advanced unresectable head and neck cancer. Treatment-related toxicity was acceptable with 50% of patients developing acute confluent mucositis. There was no severe long-term treatment-related toxicity.

Antineoplastic Agents↗