Potent interaction between glucocorticoids and growth hormone-releasing factor in vivo

Administration of dexamethasone significantly enhanced the pituitary growth hormone response to growth hormone-releasing factor in intact as well as adrenalectomized rats. Thus the inhibitory effects of glucocorticosteroids on somatic growth which involve an interaction of these steroids and growth hormone at a peripheral level may also involve a modification of pathways within the central nervous system that regulate normal growth hormone secretion.     

In vivo administration of anti-CD3 prevents malignant progressor tumor growth

Malignant progressor tumors are only weakly immunogenic and can evade host recognition and rejection. One approach to therapy involves activation of the host antitumor cellular effector mechanisms. Since monoclonal antibodies to CD3 (anti-CD3) can activate T cells in vitro, an attempt was made to determine if tumor immunity could be achieved by the administration of anti-CD3 in vivo. T lymphocytes from mice injected with anti-CD3 showed increased interleukin-2 receptor (IL-2R) expression, increased proliferation to recombinant IL-2 (rIL-2), and enhanced reactivity in both an allogeneic mixed lymphocyte reaction and a mixed lymphocyte tumor culture. Malignant tumor growth in treated mice was also examined. The anti-CD3 treatment prevented tumor outgrowth that would have killed untreated animals and also stimulated an in vivo response against a malignant progressor tumor providing lasting tumor immunity.     

Social wasps: discrimination between kin and nonkin brood

In experiments in which nest boxes were switched, colony foundresses of the social wasp Polistes fuscatus accepted sisters' combs with little brood destruction but destroyed younger brood in the combs of less closely related females and sometimes deserted these combs. Discrimination between related and unrelated brood does not appear to depend on prior brood contact or environmentally acquired cues.     

Antigenic similarity between cells transformed by ultraviolet radiation in vitro and in vivo

Cells of the 10T 1/2 mouse fibroblast line transformed in vitro by ultraviolet radiation are antigenically similar to those from skin cancers produced in mice by repeated exposure to ultraviolet radiation. Both types of tumor cells grew preferentially in ultraviolet-irradiated syngeneic mice relative to untreated animals, and both were recognized by ultraviolet radiation-induced tumor-specific suppressor lymphocytes. These properties were not shared by 10T 1/2 cells transformed in vitro by x-rays or 3-methylcholanthrene.     

茶氨酸溴香酰胺对人肝癌细胞体内外生长的抑制作用

以L-茶氨酸作对照,评估本实验室合成的新颖的茶氨酸衍生物-茶氨酸溴香酰胺（TBrC）对人肝癌HepG2细胞系体内外生长的抑制作用,并初步探究其作用的分子机制。采用MTT法检测不同浓度的TBrC对HepG2细胞体外生长的影响,应用蛋白质印迹法检测解析HepG2细胞中与癌细胞凋亡和生长密切相关蛋白的表达和药物可能作用的分子靶点。此外,建立动物肿瘤模型,与对照组茶氨酸和临床常用抗癌药物五氟尿嘧啶组相比较,评价TBrC对荷瘤裸鼠人肝癌HepG2肿瘤生长的抑制效果。实验结果显示,TBrC抑制人肝癌细胞体内外生长的活性超过其母体化合物茶氨酸分别为3倍和4倍以上,对小鼠生长无明显毒性。TBrC比茶氨酸更显著地抑制肝癌细胞生长因子受体c-Met和抗凋亡的Bcl-2等蛋白的表达;此外,TBrC大大上调促进凋亡的Bax蛋白的表达。TBrC抑制c-Met信号传导通路,下调Bcl-2/Bax蛋白比率可能是其作用的分子机制之一。这些结果提示,TBrC具有广泛应用于临床治疗和（或）辅助治疗人肝癌和其他癌症的潜力。     

CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans

Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.     

茶氨酸硝香酰胺对人宫颈癌细胞生长的抑制作用

前期研究发现本试验合成的茶氨酸衍生物茶氨酸硝香酰胺(TNC)具有显著抑制人肺癌细胞体内外生长的作用,为进一步探索研究TNC的抗癌活性和作用的分子机制,以其母体化合物茶氨酸为对照,评估现TNC对人宫颈癌细胞生长的抑制作用。采用MTT方法检测不同浓度的TNC对人宫颈癌细胞生长的影响,应用蛋白质印迹法检测解析这些癌细胞中与凋亡和生长密切相关蛋白的表达和药物可能作用的分子靶点。此外,通过建立动物肿瘤模型,评价TNC对荷瘤裸鼠体内人宫颈癌He La肿瘤生长的抑制效果。实验结果显示,TNC抑制人宫颈癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对小鼠生长无明显毒性;TNC抑制人宫颈癌细胞生长的分子机制可能与抑制VEGFR2-NF-κB信号传导通路相关。本研究结果提示,TNC具有应用于临床治疗和(或)辅助治疗高转移人宫颈癌的潜力。     

Effect of cell-cell interactions on drug sensitivity and growth of drug-sensitive and -resistant tumor cells in spheroids

Multicellular spheroids were grown from mixtures of rat brain tumor cells sensitive (9L) and resistant (R3) to 1,3-bis(2-chloroethyl)-1-nitrosourea. Percentages of each cell subpopulation in these spheroids were estimated with the sister chromatid exchange assay and were found to be approximately the same as those used to initiate spheroids. Spheroids grown from 9L cells alone had a higher growth rate than spheroids grown from R3 cells alone. However, the growth rate of mixed-cell spheroids was essentially the same as that of pure 9L spheroids and was independent of the percentages of R3 cells in mixed-cell spheroids. The sensitivity of 9L cells in mixed-cell spheroids treated with 1,3-bis(2-chloroethyl)-1-nitrosourea, estimated by changes in the number of sister chromatid exchanges per metaphase induced by treatment, decreased as the percentage of R3 cells increased. These effects are probably the result of an interaction between the two cell subpopulations held in three-dimensional contact, a situation similar to that in tumors in situ. The results suggest why one cell subpopulation of tumors does not become dominant during growth and indicate that interactions between cell subpopulations can influence the sensitivity of one subpopulation to 1,3-bis(2-chloroethyl)-1-nitrosourea.     

体外单层肿瘤细胞生长数学模型整体解的存在性

研究一个描述肿瘤生长的自由边界问题,它来源于Helen-Byrne描述的体外模拟单层肿瘤细胞连续性生长的数学模型.该模型主要研究肿瘤生长过程中细胞间的相互作用(张力和斥力)引起的内部变化.作者运用椭圆型偏微分方程的逼近方法、Lp理论和Schauder不动点理论证明了这个问题整体解的存在性.     

Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth

The hormone 17 beta-estradiol acts through its receptor system to induce MCF-7 human breast cancer cells to form tumors in athymic mice. In vitro studies have identified the production of estrogen-induced growth factors from MCF-7 cells that may have a role in growth control. These induced growth factors were sufficient to stimulate MCF-7 tumor growth in ovariectomized athymic mice, thus partially replacing estradiol. Growth factors may act as estrogen-induced "second messengers" in estrogen-responsive growth of human breast cancer.     

Thyroid hormone induction of an autocrine growth factor secreted by pituitary tumor cells

Thyroid hormones stimulate the rate of cell division by poorly understood mechanisms. The possibility that thyroid hormones increase cell growth by stimulating secretion of a growth factor was investigated. Thyroid hormones are nearly an absolute requirement for the division of GH4C1 rat pituitary tumor cells plated at low density. Conditioned media from cells grown with or without L-triiodothyronine (T3) were treated with an ion exchange resin to remove T3 and were tested for ability to stimulate the division of GH4C1 cells. Conditioned medium from T3-treated cells was as active as thyroid hormone at promoting GH4C1 cell growth but did not elicit other thyroid hormone responses, induction of growth hormone, and down-regulation of thyrotropin-releasing hormone receptors, as effectively as T3 did. A substance or substances associated with T3-induced growth stimulatory activity migrated at high molecular weight at neutral pH and was different from known growth-promoting hormones induced by T3. The results demonstrate that thyroid hormones stimulate the division of GH4C1 pituitary cells by stimulating the secretion of an autocrine growth factor.     

正确认识电子期刊与期刊全文数据库

电子期刊和期刊全文数据库是各个图书馆电子资源体系中最重要的组成部分,可是它们的内在区别却没有被充分认识,本文就此问题给予详细阐述。     

Oxygen affinity in red cells: changes induced in vivo by propranolol

Propranolol, a blocking agent for the beta adrenergic receptor, produces a redistribution of 2,3-diphosphoglycerate in the red cell. At concentrations of 3.3 x10(-5)M, 2,3-diphosphoglycerate in the red cell membrane becomes unbound in vitro. The administration of propranolol to hunmns produces similar changes and results in a decrease in the affinity of hemoglobin for oxygen.     

Rejection of tumor cells in vitro

The emergence of lymphoblast-like cells, capable of rapidly destroying tumor cells, was observed in primary cultures of an antigenic sarcoma transplantable in strain 13 guinea pigs. It is likely that these cytotoxic cells represent the progeny of lymphocytes sensitive to tutmor antigens that had infiltrated the tumor tissue.     

Ergot-induced inhibition of pituitary tumor growth in rats

Daily injections of ergocornine or ergonovine, for 3 weeks, into rats carrying a prolactin- and growth hormone-secreting pituitary tumor (MtW15) induced significant regression or inhibition of tumor growth, whereas ergocryptine had no significant effect. Ergocornine caused a decrease in cells and a disappearance or pycnosis of nuclei in the tumor tissue, and a reduced concentration of prolactin in blood.     

Tumor immunity: tumor suppression in vivo initiated by soluble products of specifically stimulated lymphocytes

Supernatant fluids of specifically stimulated lymphocyte cultures were purified. Fractions containing migration inhibition factor when injected intra-dermally into strain-2 guinea pigs produced a reaction similar in appearance to delayed cutaneous hypersensitivity. There was an accumulation of mononuclear cells at the injection sites and the growth of syngeneic tumor grafts at the sites was suppressed.     

Junctions between cancer cells in culture: ultrastructure and permeability

Cell junctions between Novikoff hepatoma cells (N1S1-67) growing as small clumps or chains in suspension culture have been studied with ultrastructural, electrophysiological, and dye-injection techniques. Cells within clumps are commonly electrically coupled and can exchange dyes with a molecular weight of 332 to 500. Gap junctions and intermediate junctions are present, whereas true tight junctions and desmosomes are absent or very rare. This system should provide a useful model for studying the properties of "communicating" junctions.     

Noncycling tumor cells: mitogenic response to antilymphocytic serum

After continuous labeling with tritiated thymidine for a period several times the cell generation time, some ELD ascites cells remained unlabeled. Despite continued exposure to tritiated thymidine, unlabeled mitoses appeared promptly after administration of mouse antilymphocytic serum. Immunosuppression released some noncycling G(2) tumor cells into mitosis.