A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma

Lessons Learned

• A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
• This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.

BackgroundThis study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical‐grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV).MethodsThis study was an open‐label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m² capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21‐day cycle. The primary endpoint was 6‐month survival rate, and secondary endpoints were progression‐free survival, overall survival, disease control rate, and safety.ResultsThirty‐nine subjects completed the study with a 46.2% stable disease rate. The median progression‐free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6‐month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha‐fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome.ConclusionOur data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.     

Purification and identification of a polysaccharide from medicinal mushroom Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor growth

Medicinal mushrooms in recent years have been the subject of many experiments searching for anticancer properties. We previously screened thirteen mushrooms for their potential in inhibiting tumor growth, and found that the water extract of Amauroderma rude exerted the highest activity. Previous studies have shown that the polysaccharides contained in the water extract were responsible for the anticancer properties. This study was designed to explore the potential effects of the polysaccharides on immune regulation and tumor growth. Using the crude Amauroderma rude extract, in vitro experiments showed that the capacities of spleen lymphocytes, macrophages, and natural killer cells were all increased. In vivo experiments showed that the extract increased macrophage metabolism, lymphocyte proliferation, and antibody production. In addition, the partially purified product stimulated the secretion of cytokines in vitro, and in vivo. Overall, the extract decreased tumor growth rates. Lastly, the active compound was purified and identified as polysaccharide F212. Most importantly, the purified polysaccharide had the highest activity in increasing lymphocyte proliferation. In summary, this molecule may serve as a lead compound for drug development.     

Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient

Calcineurin and mTOR inhibitors are commonly used immunosuppressive agents with narrow therapeutic range. As the drugs are mainly metabolized by the P450 cytochrome system, the interaction between food and herbs are also commonly seen and affect the drug levels. We present a case of a kidney transplant recipient with toxic therapeutic levels of cyclosporine A and sirolimus due to interaction between the immunosuppressive agents and Chinese herbal tea. Ingredients within the herbal tea were reported to have inhibitory effect on cytochrome CYP3A4 in-vitro studies. Transplant recipients should be alert that there may be potent interaction between the immunosuppressive drugs and herbs resulting in adverse effect on allograft function.     

Ephedra alkaloid contents of Chinese herbal formulae sold in Taiwan

Consumption of Ephedra alkaloids is prohibited in‐competition by the World Anti‐Doping Agency (WADA). In Taiwan, colds are often treated with Chinese herbal formulae containing Herba Ephedrae. We screened products sold in Taiwan and preliminarily assessed their relationships with WADA threshold violations. Fifty‐six concentrated powder products, including 19 Chinese herbal formulae that contained Herba Ephedrae, were collected. The content of Ephedra alkaloids, namely ephedrine (E), methylephedrine (ME), norpseudoephedrine (NPE; cathine), pseudoephedrine (PE), and norephedrine (NE; phenylpropanolamine), was determined using a validated high‐performance liquid chromatography method. The results revealed that the phenotypic indicators of the collected products, E/PE and E/total ratios, were 1.52–4.70 and 0.49–0.72, respectively, indicating that the Herba Ephedrae species in these products was probably E. sinica or E. equisetina, but not E. intermedia. The contents of E, ME, NPE, PE, and NE and the total alkaloid contents in the daily doses of the products were 0.45–34.97, 0.05–4.87, 0.04–3.61, 0.15–12.09, and 0.01–2.00 mg and 0.68–53.64 mg, respectively. The alkaloid contents followed a relatively consistent order (E > PE > ME ≈ NPE > NE), even for products from different manufacturers. We calculated that single doses of 50.0% and 3.6% of the products would result in the WADA thresholds of E and NPE being exceeded, respectively. Our data provide critical information for athletes and medical personnel, who should be wary of using complex Chinese herbal formulae in addition to over‐the‐counter products.     

中药膏剂对钳刮术患者术后阴道流血的作用

目的 观察中药膏剂贴敷于相关穴位对行人工流产钳刮术患者术后阴道流血的改善情况。方法 将来我院妇科行人工流产钳刮术的患者分为对照组87例和观察组82例，对照组患者按照常规人工流产钳刮术后护理方式护理；观察组同时采用中药（包括当归、川芎、三七、炮姜）制作的膏药贴敷于相关穴位（包括神阙、气海、中极穴位），观察两组患者术后不同时间阴道流血量和流血持续时间。结果 与对照组相比，观察组患者术后1h、2h及6h阴道流血量和术后阴道流血持续时间均减少（P〈0．05）。结论 采用此中药膏剂贴敷于相关穴位能减少人工流产钳刮术患者术后出血量和出血时间，促进患者术后康复。     

Skin hyperpigmentation treatment using herbs: A review of clinical evidences

Hyperpigmentation of skin is caused by several factors. UV exposure, in addition to oxidative stress, elevates inflammatory mediators stimulating melanogenesis. Herbal-derived compounds for improving skin lightness are gaining interest as they are perceived to be milder, safer, and healthier than fully synthetic products. This review briefly addresses the causes of skin hyperpigmentation and extensively summarizes the status of herbs currently used in skin-lightening cosmetics. The properties of active compounds and their dose rate information are summarized where available, along with human or animal relevant models for activity testing. This review will be of value to cosmetic formulators and dermatologists who are searching for naturally derived ingredients for improving skin lightness, in line with consumer preference and expectations.     

中药复方抗食管癌研究进展

食管癌是恶性程度高、侵袭能力强、预后较差的一类上消化道恶性肿瘤，属中医学“噎膈”范畴。中药复方在抗肿瘤方面具有显著优势。通过查阅国内外相关文献，获知构成食管癌（噎膈）的证素包括气滞、痰、气虚、血瘀、阴虚等，中医临床辨证多分为痰气交阻、气阴两虚、津亏热结、气虚痰湿、痰热互结、痰瘀互结、热毒瘀结、正虚毒蕴等，大半夏汤、启膈散、旋覆代赭汤、六君子汤、沙参麦冬汤、通幽汤等为临床常用方剂，其中启膈散、六君子汤、通幽汤等经体内外实验研究已证明可通过直接抑制肿瘤细胞增殖、或促进凋亡、影响肿瘤微环境、调节细胞能量代谢、抑制血管生成等机制发挥抗食管癌作用，且中药复方通过靶向非编码单链RNA分子（microRNA）发挥抗食管癌作用的研究越来越多，发现临床收效良好的复方大半夏汤、参赭培气汤、小陷胸汤、人参半夏汤、六神丸等尚无深入的机制研究，古籍所载的吴茱萸汤、通关散等复方却于现代少有应用。因此，该文将中医经典古籍中专药专方、现代临床常用复方及实验研究进行梳理，以期推广中药复方抗食管癌的治疗方法，发挥中西医结合治疗的协同优势。     

安眠小复方对小鼠促眠作用的机制研究

目的探讨中药安眠小复方对小鼠脑神经肽P物质(SP)及睡眠相关细胞因子的影响,以揭示其促眠作用机制。方法60只KM小鼠随机分为6组,安眠小复方高、中、低剂量组分别灌胃给予安眠小复方4.16g/kg,2.08g/kg,1.04g/kg,百乐眠组灌胃给予百乐眠胶囊0.28g/kg,地西泮组灌胃给予地西泮片1.30mg/kg,连续给药7d。末次给药30min后,处死动物,取脑组织,检测小鼠脑内神经肽SP、白介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)含量。结果与空白对照组比较,安眠小复方高、中、低剂量组均能明显降低小鼠脑组织中SP含量(P0.05或P0.01)和IL-1β含量(P0.01);安眠小复方高、中、低剂量组亦能降低小鼠脑组织中TNF-α含量,其中高、低剂量组与空白对照组比较差异有统计学意义(P0.05)。结论中药安眠小复方可能通过降低脑内SP含量、破坏觉醒中枢同时调节睡眠相关细胞因子而发挥促眠作用。