Hormone rhythms and breast cancer chronoepidemiology: salivary progesterone concentrations in pre- and post-menarchal girls and in normal premenopausal women

Orcadian and circatrigintan time series of salivary progesterone levels in premenarchal and adolescent girls and healthy mature premenopausal women have been investigated as a possible determinant for breast cancer risk. Circadian variations in progesterone appear to be more random than systematic and estimates of total daily progesterone output are better represented by samples pooled from several 2-hr specimens. Different patterns of circatrigintan progesterone secretion in girls are recognised and relate to those experienced in infertile and fertile women, though their relation to chronological or menarchal age is as yet uncertain. These data suggest that the measurement of salivary progesterone at premenarche, adolescence and maturity is a feasible, though statistically difficult, study for prospective identification of individuals at risk for breast cancer.     

蛇毒抗肝癌作用的研究

眼镜蛇毒具有抗肝癌作用.我们采用多种小鼠移植性肝癌研究了眼镜蛇毒抗肝癌作用.通过多项指标的体内实验证实眼镜蛇毒经腹腔给药,对小鼠腹水型肝癌 H_(22)(HepA)均有明显的抑制作用,其生存时间,癌重生长抑制率接近5-Fu.我们认为眼镜蛇毒是一种新型的,有一定抗癌活性药物,有在临床上进一步研究的价值.     

Incorporation of the gene for a cell-cell channel protein into transformed cells leads to normalization of growth

Summary Incorporation of the gene for connexin 43, a cell-cell channel protein of gap junction, into the genome of communication-deficient transformed mouse 10T1/2 cells restored junctional communication and inhibited growth. Growth was slowed, saturation density reduced and focus formation suppressed, and these effects were contingent on overexpression of the exogenous gene and the consequent enhancement of communication. In coculture with normal cells the growth of the connexin overexpressors was completely arrested, as these cells established strong communication with the normal ones. Thus, in culture by themselves or in coculture, the connexin overexpressor cells grew like normal cells. These results demonstrate that the cell-cell channel is instrumental in growth control; they are the expected behavior if the channel transmits cytoplasmic growth-regulatory signals.     

Alterations in Cortical [3H]Kainate and α-[3H]Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Binding in a Spontaneous Canine Model of Chronic Hepatic Encephalopathy

Excitatory amino acid receptor binding parameters were investigated in a spontaneous dog model of chronic hepatic encephalopathy. L-[3H]Glutamate, (+)-[3H]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine maleate ([3H]MK-801), [3H]kainate, and alpha-[3H]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding experiments were performed using crude cerebrocortical synaptosomal membrane preparations from dogs with congenital portosystemic encephalopathy (PSE) and control dogs. There was no change in the affinity or density of L-[3H]-glutamate or [3H]MK-801 binding sites in dogs with congenital PSE compared with control dogs. However, in the PSE dogs there was a significant reduction in the density of [3H]kainate binding sites compared with control dogs and abolition of the low-affinity [3H]AMPA binding site. The relative binding capacity of PSE synaptosomal membranes for [3H]kainate and [3H]AMPA was expressed as the ratio Bmax/KD. There was a significant inverse correlation between the Bmax/KD ratio for [3H]AMPA binding and the worst grade of encephalopathy experienced by each dog. These results suggest that there is a significant perturbation of cerebrocortical non-N-methyl-D-aspartate receptor binding in dogs with congenital PSE which may have relevance to the pathogenesis of hepatic encephalopathy.     

Roles of iron in neoplasia

Research and clinical observations during the past six decades have shown that: 1. Iron promotes cancer cell growth; 2. Hosts attempt to withhold or withdraw iron from cancer cells; and 3. Iron is a factor in prevention and in therapy of neoplastic disease. Although normal and neoplastic cells have similar qualitative requirements for iron, the neoplastic cells have more flexibility in acquisition of the metal. Excessive iron levels in animals and humans are associated with enhanced neoplastic cell growth. In invaded hosts, cytokine-activated macrophages increase intracellular ferritin retention of the metal, scavenge iron in areas of tumor growth, and secrete reactive nitrogen intermediates to effect efflux of nonheme iron from tumor cells. Procedures associated with lowering host intake of excess iron can assist in prevention and in management of neoplastic disease. Chemical methods for prevention of iron assimilation by neoplastic cells are being developed in experimental and clinical protocols. The antineoplastic activity of a considerable variety of chemicals, as well as of radiation, is modulated by iron. The present article focuses on recent findings and suggests directions for further cancer-iron research.     

Effects of excess selenomethionine on selenium status indicators in pregnant long-tailed macaques (Macaca fascicularis)

Forty pregnant long-tailed macaques were treated daily for 30 d with 0, 25, 150 or 300 μg selenium as L-selenomethionine/kg body weight. Erythrocyte and plasma selenium and glutathione peroxidase specific activities, hair and fecal selenium, and urinary selenium excretion were increased by and were linearly related to L-selenomethionine dose. Hair selenium was most sensitive to L-selenomethionine dose, with an 84-fold increase in the 300 μg selenium/(kg-d) group relative to controls (r=0.917). Daily urinary selenium excretion (80-fold,r=0.958), plasma selenium (22-fold,r=0.885), erythrocyte selenium (24-fold,r=0.920), and fecal selenium (18-fold,r=0.911) also responded strongly to L-selenomethionine. Erythrocyte and plasma glutathione peroxidase specific activities increased 154% and 69% over controls, respectively. Toxicity was associated with erythrocyte selenium >2.3 μg/mL, plasma selenium >2.8 μg/mL, and hair selenium >27 μg/g. Plasma, erythrocyte, and hair selenium concentrations may be useful for monitoring and preventing the toxicity of L-selenomethionine administered to humans in cancer chemoprevention trials.     

Out-Patient Peritoneal Lavage Cytology In the Detection of Residual Epithelial Ovarian Cancer

Peritoneal lavage fluid cytology was performed in 87 out-patients with histologically proven epithelial ovarian cancer undergoing primary management. A total of 246 peritoneal lavages were attempted, usually with temporary cannulae (n = 229). From these, 184 samples were obtained, of which 156 (85%) were suitable for cytological analysis. The sensitivity of peritoneal lavage fluid cytology in 67 patients with known residual disease was 57% whereas serum CA 125 levels were elevated in 58 (87%). Pre- and post-treatment peritoneal lavage fluid cytology had prognostic value, but this was less than that of serum CA 125 measurements.     

Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels

Summary A new low shear stress microcarrier culture system has been developed at NASA’s Johnson Space Center that permits three-dimensional tissue culture. Two established human colon adenocarcinoma cell lines, HT-29, an undifferentiated, and HT-29KM, a stable, moderately differentiated subline of HT-29, were grown in new tissue culture bioreactors called Rotating-Wall Vessels (RWVs). RWVs are used in conjunction with multicellular cocultivation to develop a unique in vitro tissue modeling system. Cells were cultivated on Cytodex-3 microcarrier beads, with and without mixed normal human colonic fibroblasts, which served as the mesenchymal layer. Culture of the tumor lines in the absence of fibroblasts produced spheroidlike growth and minimal differentiation. In contrast, when tumor lines were co-cultivated with normal colonic fibroblasts, initial growth was confined to the fibroblast population until the microcarriers were covered. The tumor cells then commenced proliferation at an accelerated rate, organizing themselves into three-dimensional tissue masses that achieved 1.0- to 1.5-cm diameters. The masses displayed glandular structures, apical and internal glandular microvilli, tight intercellular junctions, desmosomes, cellular polarity, sinusoid development, internalized mucin, and structural organization akin to normal colon crypt development. Differentiated samples were subjected to transmission and scanning electron microscopy and histologic analysis, revealing embryoniclike mesenchymal cells lining the areas around the growth matrices. Necrosis was minimal throughout the tissue masses. These data suggest that the RWV affords a new model for investigation and isolation of growth, regulatory, and structural processes within neoplastic and normal tissue.     

~(125)Ⅰ标记单抗LC-I与肺腺癌细胞体内外结合特性的研究

本文用~(125)Ⅰ标记LC-1进行了一些体内外实验。实验结果表明:LC-1单抗的结合常数为4.8×10~8M~(-1),LC-1针对的SPC-A_1细胞表面抗原的位点数为7.2×10~4/细胞;LC-1与LAC-122两单抗针对的抗原决定簇没有交叉;用蛋白酶和过碘酸钠处理SPC-A_1细胞,前者对LC-1的结合抑制39%,后者抑制66%;LC- 1不但有较强的体外结合靶细胞的能力,从LC-1在荷瘤裸鼠中的组织器官分布来看,LC-1与肿瘤有较高的体内亲和性,并且是特异性的结合。