Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin

The proliferating cell nuclear antigen (PCNA or cyclin) is a nuclear protein recently identified as a cofactor of DNA polymerase delta. When exponentially growing Balb/c3T3 cells are exposed to antisense oligodeoxynucleotides to PCNA, both DNA synthesis and mitosis are completely suppressed. A corresponding sense oligodeoxynucleotide has no inhibitory effects. These experiments indicate that PCNA (cyclin) is important in cellular DNA synthesis and in cell cycle progression.     

BCR-ABL融合蛋白融合区B细胞表位预测

以BCR-ABL融合蛋白氨基酸序列为基础,采用EMBOSS软件及DNAstar软件结合Hopp and Woods亲水性参数、Janin可及性参数、极性参数、柔韧性参数及二级结构方案对慢性粒细胞白血病BCR-ABL融合蛋白(p210~(BCR-ABL))融合区的B细胞表位进行预测。结果表明:BCR-ABL蛋白融合区位于B细胞表位内,该表位含有α-螺旋和无规则卷曲结构。BCR-ABL融合蛋白融合区B细胞表位预测的研究对应用合成肽抗原制备融合区单克隆抗体具有重要的指导意义。     

Selective inhibition of fibronectin-mediated cell adhesion by monoclonal antibodies to a cell-surface glycoprotein

Fibroblasts possess several distinct mechanisms that control cellular adhesion to extracellular matrix macromolecules. Monoclonal antibodies to a 140-kilodalton (kD) cell surface glycoprotein inhibited the adhesion of fibroblastic Chinese hamster ovary cells to fibronectin-coated substrata but did not inhibit adhesion to substrata coated with vitronectin, laminin, serum, or other adhesive macromolecules. Thus the 140-kD glycoprotein appears to be involved in the fibronectin-mediated adhesion mechanism but not in other adhesion processes.     

高良姜挥发油对人HL-60细胞株增殖及凋亡的影响

目的 研究高良姜挥发油对人HL-60细胞株增殖及凋亡的影响.方法 采用CKK-8法检测不同浓度的高良姜挥发油对HL-60细胞增殖的抑制效果,流式细胞术检测其对细胞周期的影响,并用Hoechst 33342染色法观察细胞凋亡的形态学改变.结果 高良姜挥发油可呈不同程度地剂量依赖性抑制HL-60细胞株增殖,能浓度依赖性阻滞HL-60细胞于G0/G1期,且随其浓度增加诱导细胞凋亡的形态越明显.结论 高良姜挥发油能抑制白血病细胞株HL-60的增殖,并具有阻滞细胞周期进程和诱导细胞凋亡的能力.     

Selective inhibition of tubulin synthesis by amiprophos methyl during flagellar regeneration in Chlamydomonas reinhardi

Amiprophos methyl (APM) is a strong, readily reversible and highly selective inhibitor of tubulin synthesis in Chlamydomonas reinhardi. The extensive induction of tubulin synthesis that accompanies flagellar regeneration in this organism is prevented by 3 to 10 micrometerAPM. When applied after induction has begun, APM causes a rapid cessation of tubulin synthesis. Translation studies in vitro indicate that the lack of tubulin production in APM-treated cells is not due to a direct inhibition of tubulin messenger RNA translation but rather to a selective depletion of tubulin messenger RNA.     

Virus-induced murine leukemia: its inhibition and suppression by serum containing erythropoietin

Mice infected at 2 days of age with a virus that induces reticulum cell sarcoma and myeloerythroleukemia were treated with erythropoietin-containing serum obtained from rabbits that had been treated with acetylphenylhydrazine. A marked inhibition of tumor induction occurred, particularly in females, when treatment was begun early. Delayed treatment resulted in instances of regression of overt neoplasia.     

Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors

A systematic series of low molecular weight protein tyrosine kinase inhibitors were synthesized; they had progressively increasing affinity over a 2500-fold range toward the substrate site of epidermal growth factor (EGF) receptor kinase domain. These compounds inhibited EGF receptor kinase activity up to three orders of magnitude more than they inhibited insulin receptor kinase, and they also effectively inhibited the EGF-dependent autophosphorylation of the receptor. The most potent compounds effectively inhibited the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on the EGF-independent proliferation of these cells. The potential use of tyrosine protein kinase inhibitors as antiproliferative agents is demonstrated.     

Selective phagocytosis of nucleated erythrocytes by cytotoxic amebae in cell culture

Strains of Acanthamoeba, which produce cellular damage resembling viral cytopathic effect, are known to occur in cultures of monkey kidney cells. Trophozoites of a similar strain were observed to engulf and denucleate chicken erythrocytes. Nonnucleated guinea pig erythrocytes were apparently left unchanged.     

Cell proliferation: enhancement by extracts from cell surfaces of polyoma-virus-transformed cells

Dispersion of confluent monolayers of BHK21 cells with ethylenediaminetetraacetate yields a material that inhibits cell proliferation, whereas identical extraction of polyoma-virus-transformed cells provides material which enhances cellular proliferation. The material was partially characterized.     

Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis

Many biological processes are regulated through the selective dephosphorylation of proteins. Protein serine-threonine phosphatases are assembled from catalytic subunits bound to diverse regulatory subunits that provide substrate specificity and subcellular localization. We describe a small molecule, guanabenz, that bound to a regulatory subunit of protein phosphatase 1, PPP1R15A/GADD34, selectively disrupting the stress-induced dephosphorylation of the α subunit of translation initiation factor 2 (eIF2α). Without affecting the related PPP1R15B-phosphatase complex and constitutive protein synthesis, guanabenz prolonged eIF2α phosphorylation in human stressed cells, adjusting the protein production rates to levels manageable by available chaperones. This favored protein folding and thereby rescued cells from protein misfolding stress. Thus, regulatory subunits of phosphatases are drug targets, a property used here to restore proteostasis in stressed cells.     

Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand.

In the presence of antigen presenting cells, a murine T helper (Th) cell specific for murine hemoglobin (Hb) responded to its immunogenic peptide by both cytokine (interleukin-4) secretion and proliferation. An altered Hb peptide with a single amino acid substitution induced only cytokine secretion and did not induce proliferation. Interleukin-1 costimulated and restored the Th proliferative response to normal levels. The altered peptide also supported cognate T cell-B cell interactions indicative of T cell helper function. Thus, this result suggests that the T cell receptor has the capacity of differential signaling.     

静磁场对人白血病细胞K562 DNA的损伤模式研究

【目的】研究静磁场处理对人白血病细胞DNA的损伤模式与损伤程度,为肿瘤细胞的物理治疗提供依据。【方法】以人白血病细胞K562为试材,对其进行8.8mT静磁场处理6,12,24,30,36h后,采用MTT检测细胞活力并对细胞进行计数,同时联合使用单细胞凝胶电泳以及原子力显微镜观测方法,分析经过静磁场处理后K562细胞DNA的损伤模式。【结果】K562细胞在8.8mT静磁场中处理24h,细胞生长受到抑制,细胞彗星尾长与对照相比有显著差异(P<0.05);处理时间延长到30h,尾部DNA含量和尾长与对照相比均有极显著性差异(P<0.01),表明随着静磁场处理时间的增加,K562细胞DNA的损伤模式与损伤程度发生变化。原子力显微镜观察结果显示,静磁场处理12h,K562细胞DNA已经发生损伤,细胞DNA分子的平均高度增加,平均长度减小;静磁场处理24h,DNA链变短变粗,小片段DNA明显增多,部分DNA发生断裂;静磁场处理36h,细胞DNA形态发生显著变化,DNA大部分断裂成小片段,小片段DNA之间相互交联成板状聚集体。【结论】8.8mT静磁场对K562细胞有杀伤效应,并且这种杀伤作用具有随处理时间延长而累积的效应。随着静磁场处理时间的延长,细胞DNA经历了解链-断裂-交联和断裂并存的变化过程,DNA损伤程度亦逐步加剧。     

Immunity to colon cancer assessed by antigen-induced inhibition of mixed mononuclear cell migration

A purified preparation of mixed human peripheral blood lymphocytes and monocytes was used in an inhibition-of-migration assay for cell-mediated immunity to cancer of the colon. This preparation was reproducibly antigen-responsive and migrated with greater reliability than did a more complex cell mixture. Of 27 patients with this disease, cells from 24 showed inhibited migratio in response to colon carcinoma antigen. Uninhibited migration patterns were found in each of the 52 cancer-free controls, including eight patients with nonmalignant disease initially diagnosed as cancer of the colon, and in nine patients with surgically cured adenocarcinoma of the colon.     

Human T cell leukemia viruses use a receptor determined by human chromosome 17

Human T cell leukemia viruses (HTLV-I and HTLV-II) can infect many cell types in vitro. HTLV-I and HTLV-II use the same cell surface receptor, as shown by interference with syncytium formation and with infection by vesicular stomatitis virus (VSV) pseudotypes bearing the HTLV envelope glycoproteins. Human-mouse somatic cell hybrids were used to determine which human chromosome was required to confer susceptibility to VSV(HTLV) infection. The only human chromosome common to all susceptible cell hybrids was chromosome 17, and the receptor gene was localized to 17cen-qter. Antibodies to surface antigens known to be determined by genes on 17q did not block the HTLV receptor.     

Zeylenone对急性淋巴细胞白血病细胞增殖及凋亡的影响

目的探讨Zeylenone体外抗急性淋巴细胞白血病(Acute Lymphoblastic Leukemia,ALL)效应及作用的可能机制。方法应用MTT法比较Zeylenone对肿瘤细胞、正常细胞增殖的影响;AO/EB染色观察其对ALL细胞(Reh、RS4;11)凋亡形态学的改变;流式细胞仪检测药物对细胞凋亡及细胞周期的影响。结果 Zeylenone对多种细胞呈现增殖抑制作用,且对ALL细胞株呈现更高的敏感性,而对外周血单个核细胞(Peripheral blood mononuclear cell,PBMC)抑制作用较小,抑制Reh、RS4;11细胞增殖呈时间依赖性和剂量依赖性;Zeylenone能够诱导ALL细胞凋亡,阻滞细胞周期于G0/G1期。结论 Zeylenone体外具有抗ALL细胞增殖的作用,其作用与诱导细胞凋亡、阻滞细胞周期相关。     

G1 events and regulation of cell proliferation

Cells prepare for S phase during the G1 phase of the cell cycle. Cell biological methods have provided knowledge of cycle kinetics and of substages of G1 that are determined by extracellular signals. Through the use of biochemical and molecular biological techniques to study effects of growth factors, oncogenes, and inhibitors, intracellular events during G1 that lead to DNA synthesis are rapidly being discovered. Many cells in vivo are in a quiescent state (G0), with unduplicated DNA. Cells can be activated to reenter the cycle during G1. Similarly, cells in culture can be shifted between G0 and G1. These switches in and out of G1 are the main determinants of post-embryonic cell proliferation rate and are defectively controlled in cancer cells.