Modern approaches to the treatment of breast cancer

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.     

缺血性脑损伤诱导内源性神经干细胞的增殖和迁移

目的:观察缺血性脑损伤对内源性神经干细胞增殖、迁移的影响。方法:实验于2004-09/2005-03在新乡医学院人体解剖与组织胚胎重点实验室进行。10～12周体质量300～350g的健康雄性SD大鼠62只,由新乡医学院实验动物中心提供。按随机数字表方法将其分为正常组6只、假手术对照组14只、脑缺血再灌注组42只(分为再灌注1,3,5,7,10,15,20d7个时间点,每时间点6只)。参照Pulsinelli-Brierley法,夹闭大鼠双侧颈总动脉制作短暂性全脑缺血动物模型,全脑缺血10min后再灌注,假手术对照组不夹闭颈总动脉。于脑缺血再灌注不同时间点应用SABC免疫组化法染色显示5-溴-2-脱氧尿嘧啶阳性细胞和巢蛋白阳性细胞,光镜下观察并分析脑缺血损伤后内源性神经干细胞增殖、迁移的变化过程。结果:正常组、假手术对照组大鼠均存活,脑缺血再灌注组大鼠1d、5d、15d、20d各死亡1只,共58只大鼠进入结果分析。①正常组与假手术对照组室管膜下区、海马CA1区、齿状回区域均偶见5-溴-2-脱氧尿嘧啶阳性细胞和巢蛋白阳性细胞。②脑缺血再灌注后1d于海马、齿状回和室管膜下区均有5-溴-2-脱氧尿嘧啶阳性细胞和巢蛋白阳性细胞,随后逐渐增加,7～10d达高峰,术后20d仍有表达;在室管膜下区的5-溴-2-脱氧尿嘧啶阳性细胞和巢蛋白阳性细胞有向皮质、海马迁移的现象。结论:成年大鼠全脑缺血后7～10d内源性神经干细胞增殖达到高峰;增殖的内源性神经干细胞存在由增殖区向靶区迁移的现象。     

Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection

International Urology and Nephrology - To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with...     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

Effects of IL-6 variants in multiple myeloma: growth inhibition and induction of apoptosis in primary cells

Interleukin-6 (IL-6) plays a pathogenetic role in B-cell malignancies and is a growth factor for multiple myeloma (MM) cells. Elevated serum IL-6 levels and a higher proliferative activity of bone marrow plasma cells are poor prognostic factors in MM patients. In addition to clinical trials with anti-IL-6 monoclonal antibodies, an alternative therapeutic approach based on the use of IL-6 receptor (R) super-antagonists (Sants) has been proposed. Sants are variants of the native cytokine characterized by a wild type affinity for the ligand-specific receptor chain IL-6R alpha and by a reduced ability to bind and/or dimerize the signaling chain gp-130. We report the in vitro effects of four different Sants on cell kinetic modulation and induction of apoptosis of primary cells from MM patients. Ten MM samples were cultured in the presence of four different Sants and heterogeneous effects in terms of reduction of proliferation and induction of apoptosis could be observed. A decrease of the S phase cells (> or = 25%) coupled with the induction of apoptosis was obtained in 4/10 samples: three of these samples had a diploid DNA stem line and an inferior initial percentage of S phase cells. Serum IL-6 concentrations did not correlate with the anti-proliferative activities of the Sants. Cell growth inhibition was observed especially in samples with soluble IL-6R serum concentrations > 200 ng/ml. We conclude that Sants can exert antiproliferative effects on selected MM samples. Such effects may depend on the availability of large amounts of soluble IL-6R. Further studies should aim at defining the conditions necessary for optimal antiproliferative activity.     

Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1

Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains, capable of mediating diverse protein-protein interactions. GRIP1 has been implicated in the regulation of neuronal synaptic function, but its physiologic roles have not been defined in vivo. We find that elimination of murine GRIP1 results in embryonic lethality. GRIP1(-/-) embryos develop abnormalities of the dermo-epidermal junction, resulting in extensive skin blistering around day 12 of embryonic life. Ultra-structural characterization of the blisters (or bullae) revealed cleavage of the dermo-epidermal junction below the lamina densa, an alteration reminiscent of the dystrophic form of human epidermolysis bullosa. Blisters were also observed in the lateral ventricle of the brain and in the meninges covering the cerebral cortex. These genetic data suggest that the GRIP1 scaffolding protein is required for the formation and integrity of the dermo-epidermal junction and reveal the importance of PDZ domains in the organization of supramolecular structures essential for mammalian embryonic development.