Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity,in node-negative breast carcinoma

In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03).With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS)(Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 ( 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (– vs +/++; p = 0.041); tumor size (pT1 vs pT2–3; p = 0.042) and grading (GI vs GII–III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic.In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age ( 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model.In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.     

PDGF-B链基因三链形成寡核苷酸对C6胶质瘤细胞增殖和细胞周期的影响

目的观察PDGF-B链基因三链形成寡核苷酸(triplex-forming oligonucleotide,TFO)对C6胶质瘤细胞增殖和细胞周期的影响.方法应用免疫荧光流式细胞技术观察PDGF-B链基因TFO对C6胶质瘤细胞PDGF-B、PCNA表达的影响.应用流式细胞技术观察PDGF-B链基因TFO对C6胶质瘤细胞细胞周期的影响.结果 PDGF-B链基因TFO对C6胶质瘤细胞PDGF-B链基因、PCNA的表达有明显抑制作用,而且抑制作用存在浓度依赖性.PDGF-B链基因TFO能使C6胶质瘤细胞S期的百分率明显降低,阻止细胞由静止期(G0-G1期)进入(S期).结论 PDGF-B链基因TFO能够抑制C6胶质瘤细胞PDGF-B链基因的表达,阻碍细胞进入S期,降低细胞增殖能力.     

结直肠癌组织中Survivin表达与细胞增殖的关系

目的 :探讨结直肠癌组织中Survivin表达的临床病理学意义及其与癌细胞增殖的关系。方法 :免疫组织化学染色方法 (SP法 )检测 10 6例结直肠癌组织中Survivin、Ki 6 7、P5 3的表达 ,分析Survivin表达与Ki 6 7增殖指数、P5 3表达及各临床病理因素的关系。结果 :Survivin阳性表达结直肠癌的Ki 6 7增殖指数 (4 1.31%± 19.83% )明显高于Survivin阴性者 (2 6 .2 1%± 2 0 .36 % ) ,Survivin表达与肿瘤细胞增殖呈正相关 (P <0 .0 5 )。Survivin表达与P5 3表达无显著相关。Survivin在结直肠癌组织中的表达率为 6 4 .2 % (6 8/10 6例 ) ,癌旁形态学正常的结直肠粘膜未见Survivin表达 ;Survivin在中高分化结直肠癌表达阳性率 72 .4 % (6 3/87例 ) ,明显高于低分化结直肠癌 (2 6 .3% ,5 /19例 ) ,P <0 .0 5。此外 ,Survivin表达与患者性别、肿瘤位置、浸润深度、淋巴结转移、远处转移以及Dukes’分期无显著相关 (P >0 .0 5 )。结论 :凋亡抑制蛋白Survivin在结直肠癌组织中阳性表达率为 6 4 .2 % ,与细胞分化程度有关 ,可促进结直肠癌细胞的增殖     

癌基因、妊娠性滋养细胞增生与葡萄胎恶变关系的研究

目的：探讨癌基因、妊娠性滋养细胞增生程度与葡萄胎恶变的关系。方法：采用针对Ｃ－Ｈａ－ｒａｓ及Ｃ－ｅｒｂＢ２基因表达产物Ｐ２１和Ｐ１８５的单克隆抗体进行免疫组织化学染色。检测８２例葡萄胎中两种基因产物的表达情况，经２年以上随访证实未发生恶变３２例为非恶变组，经手术和临床证实发生恶变５０例为恶变组，其中３５例行手术治疗。结果：恶变组Ｐ２１的表达程度低于非恶变组（Ｐ＝０．００８２）；Ｐ１８５的表达显著高于非恶变组（Ｐ＝０．００２８）。手术治疗的３５例中，恶变后两种基因产物的表达改变较恶变前更明显。两组葡萄胎中滋养细胞增生程度差异无显著性（Ｐ＝０．４１３）。不同来源的绒毛膜癌（绒癌）之间及绒癌与侵蚀性葡萄胎（侵葡）之间，Ｐ２１和Ｐ１８５的表达差异亦无显著性（Ｐ＝０．２６８，Ｐ＝０．７１９）。结论：Ｐ２１的低表达及Ｐ１８５的高表达与葡萄胎恶变有关，但与其恶性转化方向无关；滋养细胞增生程度与葡萄胎恶变亦无关。     

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer

Increased dietary fat intake and rate of breastepithelial cell proliferation have each been associated withthe development of breast cancer. The goal ofthis study was to measure the effect ofa low fat, high carbohydrate diet on therate of breast epithelial cell proliferation in womenat high risk for breast cancer. Women wererecruited from the intervention and control groups ofa randomized low fat dietary intervention trial, breastepithelial cells were obtained by fine needle aspiration,and cell proliferation was assessed in these samplesusing immunofluorescent detection of Ki-67 and PCNA. Theeffects of needle size and study group oncell yield and cytologic features of the cellswere also examined. Fifty three women (20 inthe intervention group and 33 in the controlgroup) underwent the biopsy procedure. Slides from 38subjects were stained for Ki-67 and from 14subjects for PCNA. No cell proliferation (fluorescence) wasdetected for either Ki-67 or PCNA in anyof the slides. Epithelial cell yield and numberof stromal fragments were greater with a largerneedle size. Numbers of stromal fragments and bipolarnaked nuclei were greater in the low fatas compared to the control group but nodifferences in epithelial cell yield were observed betweenthe two groups. This study confirms that fineneedle aspiration biopsy is a feasible method ofobtaining epithelial cells from women without discrete breastmasses, but suggests that cell proliferation cannot beassessed using Ki-67 and PCNA in such samples.     

Role of sialoglycan structures for the function of the epidermal growth factor receptor and the in vitro proliferation of head and neck cancer

Squamous cell carcinomas of the head and neck have been found to show a high expression of the receptor for epidermal growth factor (EGF). This overexpression of the receptor has been associated with malignant transformation of cells, although there is still debate as to what extent this receptor takes part in the proliferation of malignant cells and which function it fulfills. The factors which determine receptor-ligand interaction are also not clearly defined. That the extracellular domain of the EGF receptor carries carbohydrate or sialoglycan structures might be important for function of the receptor. Since tumor specific enzymes can possibly alter such structures, it was the aim of our study to investigate the role of these structures on the EGF receptor during the proliferation of head and neck carcinomas. We used the human laryngeal squamous carcinoma cell line HLaC 79 and altered, for the first time, specific glycan structures with sialidase α-2,3 and α-2,6, causing desialylation. Changes were also produced by endo-β-galactosidase and sialyltransferase. Findings were monitored by labeling with bromo-deoxyuridine. To determine receptor affinity, ¹²⁵I-labeled EGF was employed. Results showed that both cell proliferation and receptor affinity depended on the level of sialylation of the receptor carbohydrate side chains. Desialylation led to a statistically significant reduction of tumor cell proliferation to 65 ± 33% (P < 0.01), while receptor affinity decreased to 70 ± 26% (P < 0.01).The importance of EGF receptor for the proliferation of malignant cells seems to depend on the level of sialylation of glycan structures on receptor protein. A release of enzymes by tumor cells may then produce auto-control of tumor proliferation on its own. Received: 5 November 1997 / Accepted: 21 April 1998     

Growth and survival of B-chronic lymphocytic leukaemia cells

Although chronic lymphocytic leukaemia of B-cell type (B-CLL) is the most common form of leukaemia in the Western world, several questions about the biology of B-CLL remain to be clarified. To obtain a conceptual model for B-CLL, defined as a relentless accumulation of resting B-CLL cells, it is particularly relevant to ask which cell type is the normal counterpart of B-CLL; what is the site of proliferation; which signals are involved in the recruitment and induction of proliferation and which signals contribute to the survival of the B-CLL cells? The significance of the studies on B-CLL cellsin vitro for the interpretation of thein vivo situation may be questioned since they oversimplify the multiple and complex cellular interactions that occurin vivo. However, thein vitro studies have been instrumental in elucidating signals that may regulate growth, differentiation and survival of B-CLL cells. This knowledge, herein reviewed, can be used to put forward a hypothesis on B-CLL cell regulationin vivo.     

Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids

The interaction between the estrogen receptor and a variety of flavonoids was studied in the presence or absence of estradiol using a stably-transfected human breast cancer cell line (MVLN). On the other hand, flavonoids were evaluated for their effects on proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions and/or substituents essential for estrogenic or antiestrogenic activities. In contrast, we did not find the same relationship for cell proliferation. Among all flavonoids used, only 7-methoxyflavanone and 7,8-dihydroxyflavone at high concentrations (50 μM) possess antiestrogenic and antiproliferative activities. These results suggest that two hydroxyls (in positions 7 and 8) or 7-methoxy substituents are essential for the antiestrogenic activity of flavonoids. However, it seems that flavonoids at high concentrations exert their antiproliferative activity through other estrogen receptor-independent mechanisms.     

Initial transforming event in myelodysplastic syndromes may be viral: case for cytomegalovirus

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders which begin in a pluripotential bone marrow (BM) stem cell. This early stem cell is believed to acquire a growth advantage over its neighbors as a result of an initial transforming event, the nature of which has remained obscure. In this paper, we propose that pathogens such as those belonging to the herpesvirus family of DNA viruses may play a role in the initial transformation of the stem cell. The case for cytomegalovirus (CMV) as a representative of this family of viruses is discussed at length and a molecular mechanism which may be involved in the oncogenic activity of CMV is proposed. No proof has been presented to implicate CMV directly in MDS, but circumstantial evidence which supports such a possibility is provided.