Growth suppression of HER2-overexpressing breast cancer cells by berberine via modulation of the HER2/PI3K/Akt signaling pathway

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. This study investigated the molecular mechanisms by which BBR suppresses the growth of HER2-overexpressing breast cancer cells. The results show that BBR induces G1-phase cell cycle arrest by interfering with the expression of cyclins D1 and E and that it induces cellular apoptosis through the induction of a mitochondria/caspase pathway. The data also indicate that BBR inhibits cellular growth and promotes apoptosis by down-regulating the HER2/PI3K/Akt signaling pathway. Furthermore, it is also shown that a combination of taxol and BBR significantly slows the growth rate of HER2-overexpressing breast cancer cells. In conclusion, this study suggests that BBR could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.     

Pretreatment with an ethanolic extract of Taiwanofungus camphoratus (Antrodia camphorata) enhances the cytotoxic effects of amphotericin B

Taiwanofungus camphoratus, a well-known Chinese medicine used in Taiwan, possesses several pharmacological functions, including anticancer effects. In the present study, we aimed to investigate a novel anticancer effect by pretreating cancer cells with an ethanolic extract of T. camphoratus (TCEE) followed by the administration of an antifungal agent amphotericin B (AmB). Both TCEE and AmB showed significant dose-dependent cytotoxicity in HT29 cells. Pretreatment with a nontoxic dose of TCEE enhanced the cytotoxicity of AmB. Furthermore, significant apoptotic cell death was found in cells treated with TCEE and AmB. A combination treatment with AmB plus TCEE resulted in a significant repression of tumor growth in HT29 xenografts. Collectively, our results indicated that combined treatment with AmB and TCEE effectively induced apoptosis and inhibited tumor growth. In the future, TCEE may serve as a potential complementary and alternative medicine to treat patients suffering from colorectal cancer.     

Gallic acid induces G2/M phase arrest of breast cancer cell MCF-7 through stabilization of p27(Kip1) attributed to disruption of p27(Kip1)/Skp2 complex

Gallic acid (GA), 3,4,5-trihydroxybenzoic acid, is a natural polyphenolic acid and widely found in gallnuts, tea leaves and various fruits. Previous studies have shown that GA possesses anti-inflammatory, antiallergic and anticarcinogenic activity. In the present study, we aim to investigate the antitumor effects of GA on breast cancer cell. Our results revealed that GA treatment significantly reduced the cell growth of human breast cancer cell MCF-7 in a dose-dependent manner. Further flow cytometric analysis showed that GA induced significant G2/M phase arrest but slightly affected the population of sub-G1MCF-7 cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, CDK2, cyclin B1 and cdc2/CDK1 were diminished; in contrast, levels of the negative regulators p27(Kip1) and p21(Cip1) were increased by GA treatment. Additionally, Skp2, a specific ubiquitin E3 ligase for polyubiquitination of p27(Kip1) was reduced by GA treatment. Further investigation showed that GA attenuated Skp2-p27(Kip1) association and diminished polyubiquitination of p27(Kip1) in MCF-7 cells. Moreover, knockdown of p27(Kip1) but not p21(Cip1) significantly alleviated GA-induced accumulation of G2/M phase. These findings indicate that GA may upregulate p27(Kip1) level via disruption of p27(Kip1)/Skp2 association and the consequent degradation of p27(Kip1) by proteosome, leading to G2/M phase arrest of MCF-7 cell. It is suggested that GA should be beneficial to treatment of breast cancer and p27(Kip1)-deficient carcinomas.     

Compartmentalized and binary behavior of terminal dendrites in hippocampal pyramidal neurons

The dendritic arbor of pyramidal neurons is not a monolithic structure. We show here that the excitability of terminal apical dendrites differs from that of the apical trunk. In response to fluorescence-guided focal photolysis of caged glutamate, individual terminal apical dendrites generated cadmium-sensitive all-or-none responses that were subthreshold for somatic action potentials. Calcium transients produced by all-or-none responses were not restricted to the sites of photolysis, but occurred throughout individual distal dendritic compartments, indicating that electrogenesis is mediated primarily by voltage-gated calcium channels. Compartmentalized and binary behavior of parallel-connected terminal dendrites can greatly expand the computational power of a single neuron.     

以电化学分析法探讨堆肥对土壤三价砷活性的影响

台湾西南沿海地区土壤中砷含量有偏高情形，砷含量过高会经由各种途径对人体造成毒害。以X-射线绕射仪与傅立叶转换红外线吸收光谱仪证明普鲁士蓝封三价砷的专一性吸附机制．再以普鲁士蓝修饰电极搭配流动注入系统来侦测土壤三价砷．并探讨堆肥对三价砷在不同土壤中吸附与脱附的影响。试验结果得知电化学分析技术可快速、简便且准确地侦测土壤三价砷。且结果中也指出堆肥处理会增加秀水与後里土壤对三价砷的吸附。此外。三种土壤不论有无施用堆肥，脱附百分率的大小顺序为兴大〉秀水〉后里．其中秀水土壤虽在施用堆肥後吸附力大小明显增加．但脱附百分率下降的情形较不明显．显示黏土矿物种类与含量控制三价砷的脱附行为。     

The effect of progesterone supplementation post mating and shearing of ewes in early pregnancy on the reproductive performance of ewes and birthweight of lambs

AIM: To determine whether short-term progesterone supplementation post mating or shearing of ewes in early pregnancy affected either the proportion of ewes that lambed or that had multiple lambs, or the birthweight of lambs.

METHODS: Romney ewes (n=457) were synchronised in oestrus using controlled internal drug-releasing (CIDR) devices containing progesterone, and mated to Romney rams over a 5-day period. The mid-point of mating (Day 0) occurred 2 days after the withdrawal of CIDR devices. Ewes mated (n=397) were randomly allocated to one of four treatment groups: shearing at Day 5, shearing at Day 30, no shearing, and no shearing plus progesterone supplementation using a CIDR device inserted on Day 3 for 6 days. During the period from Day 5 to Day 27, six harnessed Suffolk rams were placed with the ewes and matings recorded. At Day 48, all ewes that did not return to the Suffolk rams were scanned for pregnancy using ultrasound. At Day 140, single- and multiple-bearing ewes were set-stocked at 15.1 and 12.2 ewes/ha, respectively, and equivalent numbers of ewes from each treatment group were placed in each paddock. Blood samples from 10 unshorn and 10 progesterone-supplemented ewes were collected on Days 3, 6 and 9, and analysed for plasma progesterone concentrations. Lambs were identified to their dam and weighed within 12 h of birth, and again at 27 and 93 days after the mid-point of lambing. The ewes were weighed at regular intervals throughout the trial.

RESULTS: Plasma progesterone concentrations of supplemented ewes were higher than those of unsupplemented ewes (3.28 vs 1.75 ng/ml) on Day 6 (p=0.02) but not on Day 9 (4.58 vs 4.63 ng/ml). Treatment of ewes had no effect on either the proportion of ewes which lambed to the synchronised mating period or that had multiple lambs. Lambs born to ewes shorn at Day 30 tended (p=0.09) to be heavier at birth (by 0.28 kg) than those born to unshorn ewes but this effect was not evident when data were corrected for length of gestation. Neither shearing at Day 5 nor progesterone supplementation had any effect on the birthweight of lambs, and the treatment of ewes had no effect on the survival rate of lambs to weaning.

CONCLUSIONS: Progesterone supplementation for 6 days beginning 3 days post mating did not increase either the proportion of ewes that lambed or that had multiple lambs, or the birthweight of lambs. Shearing 5 days after mating had no significant effect on the reproductive performance of ewes and need not be avoided, but is unlikely to result in an increase in lamb birthweight. Shearing ewes at Day 30 may result in an increase in the birthweight of lambs but, ideally, ewes should be further advanced in pregnancy before shearing is undertaken.     

The effect of individual liveweight and condition scores of ewes at mating on reproductive and scanning performance

Abstract

AIMS: To determine the effects of liveweight (LW) and condition score (CS) of ewes at mating on both mating performance and scanning percentage, and to determine if effects of CS were independent of LW.

METHODS: Two groups of ewes, comprising 1,780 mixedaged Romney (Rom MA) and 692 composite two-tooth (? East Friesian 1/16 Finn 13/16 Romney, Comp TT) ewes were grazed separately with harnessed rams for two reproductive cycles. Romney rams were used for the first 17 days of mating and then replaced on the morning of Day 18 by Suffolk rams. Ewes were weighed and CS assessed on a scale of 0–5 before the introduction of the rams. Ewes were identified as having been mated during the first cycle only, during both cycles, during the second cycle only, or not mated. All mated ewes were scanned using ultrasound, 50 days after the end of mating, and identified as being either non pregnant, single-, twin- or triplet-bearing.

RESULTS: Linear relationships (R²=0.99) between mean LW and CS at mating were evident for both Rom MA and Comp TT ewes and the mean increase in LW per unit increase in CS was greater in the Rom MA ewes (7.88 kg) than the Comp TT (4.78 kg) ewes (p<0.05). Ewes mated in the second cycle only were significantly (p<0.05) lighter than those mated in the first cycle only. In Rom MA ewes, a greater proportion were mated in the first cycle only if CS was .2.0 than if CS was <2.0, and the proportions of ewes mated in the first cycle only or in both cycles did not differ if CS was ≥2.5. In Comp TT ewes, there was no difference in the proportions mated in the first cycle or both cycles, if CS was ≥2.0. Triplet-bearing ewes were heavier than twin-bearing ewes, which were in turn heavier than both singleton-bearing and non pregnant ewes. Twin-bearing ewes had higher CS than both single-bearing and non pregnant ewes (p<0.05) but differences were not significant if LW was included as a covariate. In both Rom MA and Comp TT ewes, greater proportions were non pregnant and lower proportions had twins if CS was <2.0 than if CS was ≥2.0. In Rom MA ewes only, a greater proportion again had twins and a lower proportion had singletons if CS was ≥3.0 than if CS was <3.0. In Comp TT ewes, the proportion that were non pregnant or twin-bearing did not vary with CS if CS was ≥2.0. Reproductive performance was maximal for Rom MA and Comp TT ewes that had CS at mating ≥3.0 and ≥2.0, respectively, equating to LW of 62.6 and 48.5 kg, respectively.

CONCLUSIONS: In both groups of ewes, CS and LW at mating positively affected reproductive performance measured at the time of mating and at scanning, however, no reproductive advantage was evident above a minimum CS of 3.0 and 2.0, equating to LW of 62.6 and 48.5 kg, for Rom MA and Comp TT ewes, respectively. Sheep farmers should direct management to ensure that no ewes are below these minimum targets rather than ensuring high average LW and/or CS of a mob.     

Identifying factors which maximise the lambing performance of hoggets: a cross sectional study

AIM: To identity perceptions of farmers with respect to advantages of hogget lambing and to identify optimal management strategies for hogget lambing used in New Zealand.

METHODS: A questionnaire was sent to 1,038 sheep farmers in New Zealand who had indicated their hoggets would be lambing in 2002. Information was gathered on the practice of hogget lambing in New Zealand, in particular on the numbers and breeds of hoggets and rams used, selection criteria used for hoggets, use of teasers (vasectomised rams), length of mating period, use of mating crayons, vaccinations, medications and mineral supplements given, level of feed offered, use of pregnancy scanning, management during pregnancy and lambing, number of lambs present at docking, and shearing policies for hoggets. Farmers were also asked to indicate the relative importance of five stated reasons for choosing to have their hoggets mated in 2002.

RESULTS: A total of 629 (60.6%) responses were incorporated in the analysis, and the average percentage of hogget lambing was 60%. Use of vaccinations, length of the mating period, number of rams used, breed of hogget, weight at mating, management during lactation, and shearing policy were associated (p<0.05) with the lambing performance of hoggets, in the multivariate analysis.

CONCLUSIONS: This study indicated that to ensure high lambing percentages (LP) in hoggets in New Zealand, sheep farmers should: vaccinate hoggets against toxoplasmosis and campylobacteriosis; utilise a 40-day mating period; use 2.6–3.5% of rams during mating; incorporate Finn or East Friesian genetics; ensure liveweights at mating are as high as possible; manage single- and multiple-bearing/-rearing hoggets separately during the lambing and lactation periods; and shear hoggets pre-mating.