血管内皮细胞条件培养基促进胃癌细胞增殖和迁移

探讨血管内皮细胞培养基对胃癌细胞增殖和迁移的影响,分析血管内皮细胞调控胃癌细胞发生转移的机制。方法 设置对照组和共培养组,分别将正常培养基和人脐静脉血管内皮细胞HUVEC条件培养基作用于胃癌细胞HGC27,采用MTT法和划痕试验检测胃癌细胞HGC27的增殖活性和迁移能力。设置Control组、6 h组、12 h组和24 h组,以HUVEC的条件培养基作用于胃癌细胞6、12和24 h,Western blot检测EMT标志物和紧密连接蛋白的表达变化,激光共聚焦显微镜观察细胞骨架和紧密连接蛋白的分布变化。结果 MTT及划痕试验表明HUVEC条件培养基促进胃癌细胞HGC27的增殖和迁移。与Control组比较,间接共培养后胃癌细胞的形态呈间充质状改变,丝状伪足样凸起数量显著增加。 Western blot结果显示间接共培养后胃癌细胞上皮标志物E-cadherin表达水平逐渐下降,而间充质标志物N-cadherin和MMP-9逐渐增加,具有时序性变化规律。ZO-1和Occludin的表达也逐渐下降,细胞膜分布减少。结论 间接共培养下,血管内皮细胞通过上调胃癌细胞MMP-9,破坏紧密连接,促进胃癌细胞增殖和迁移     

胃癌术前淋巴结转移评估方法研究进展

胃癌在我国的发病率及病死率较高,目前,手术仍然是胃癌的主要治疗方式。术前诊断淋巴结转移对于胃癌手术方式的选择有着重大意义。目前,临床中对于胃癌术前淋巴结转移的诊断尚没有金标准。本文对胃癌术前淋巴结转移评估方法的研究进展进行综述。     

FANCD2、PALB2表达水平与非小细胞肺癌临床特征及预后的关系

目的 探讨范科尼贫血D2蛋白（FANCD2）、乳腺癌易感基因2定位协作蛋白（PALB2）表达水平与非小细胞肺癌（NSCLC）临床特征及预后的关系。方法 选取2017年11月—2019年10月成都市第二人民医院收治的194例NSCLC患者作为研究对象。将手术过程中取得癌组织标本作为NSCLC组,将对应的癌旁组织标本作为癌旁组,每组194例。采用免疫组织化学法检测FANCD2、PALB2在NSCLC患者癌组织及癌旁组织中的表达情况;分析FANCD2、PALB2表达与NSCLC患者临床病理特征的关系;采用Kaplan-Meier法绘制生存曲线,采用Cox比例风险模型分析探讨NSCLC患者预后的影响因素。结果 NSCLC组FANCD2、PALB2阳性率高于癌旁组（P <0.05）。Spearman相关性分析显示,NSCLC患者癌组织中FANCD2蛋白与PALB2蛋白呈正相关（r_s =0.486,P <0.05）。不同年龄、性别、吸烟、组织学分型、肿瘤直径患者FANCD2、PALB2阳性率比较,差异均无统计学意义（P >0.05）。TNM分期为Ⅲ、Ⅳ期,低分化,有淋巴结转移患者高于TNM分期为I、Ⅱ期,中/高分化,无淋巴结转移患者（P <0.05）。多因素逐步Cox回归分析结果显示：TNM分期Ⅲ、Ⅳ期［H^R=4.125,（95% CI：2.187,10.035）］、低分化［H^R=3.146,（95% CI：3.115,9.264）］、淋巴结转移［H^R=4.124,（95% CI：3.005,13.145）］、FANCD2阳性［H^R=5.146,（95% CI：3.784,12.689）］、PALB2阳性［H^R=4.563,（95% CI：2.845,7.398）］是NSCLC患者复发的影响因素（P <0.05）。多因素逐步Cox回归分析结果显示,TNM分期Ⅲ/Ⅳ期［H^R=3.689,（95% CI：2.963,11.254）］、低分化［H^R=2.167,（95% CI：1.998,5.996）］、淋巴结转移［H^R=5.648,（95% CI：3.552,12.953）］、FANCD2阳性［H^R=3.886,（95% CI：2.958,12.775）］、PALB2阳性［H^R=4.633,（95% CI：1.968,11.547）］是NSCLC患者预后的影响因素（P <0.05）。FANCD2阳性患者与阴性患者生存率比较,差异有统计学意义（P <0.05）;PALB2阳性患者与阴性患者的生存率比较,差异有统计学意义（P <0.05）。结论 FANCD2、PALB2在NSCLC患者癌组织中呈高表达,与TNM分期、分化程度、淋巴结转移密切相关,可作为辅助评估患者预后和复发的潜在标志物。     

Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer

Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects.The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/-hydroxymetoprolol).The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.     

Primary breast sarcoma: A review of 33 cases with immunohistochemistry and prognostic factors

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas).All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy.Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer.Immunohistochemistry was disappointing for identification of specific histologic sub-types.     

Phase I study of 4′-deoxydoxorubicin (esorubicin) in children with malignant solid tumors

Summary 4 -Deoxydoxorubicin was given to 15 patients with drug-resistant pediatric malignant solid tumors with the objectives of determining the maximum tolerated dosage and dose-limiting toxicity. Maximum tolerated dosage was 36 mg/m₂ given IV once every 3 weeks. Dose limiting toxicity was myelosuppression, which was severe and prolonged. Therapeutic benefits were not observed for these patients.     

2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo

Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. -Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.Dr. Upp was awarded a fellowship grant from the American Cancer Society Texas Division.     

The Stockholm breast cancer screening trial — 5-year results and stage at discovery

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40–64 years. A breakdown by age suggests an effect in age group 50–59 years, but not yet in age groups 40–49 and 60–64 years.When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the hidden number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p<0.05). According to this it could be important to add the estimated number of undetected, hidden cases in the control group in order to utilize the difference in detection rate in the screening- and control group respectively.     

Polypeptide composition of normal and neoplastic human breast tissues and cells analyzed by two-dimensional gel electrophoresis

Summary The protein populations of epithelial cells cultured from two neoplastic and five non-neoplastic human breast tissues were resolved and displayed by two-dimensional polyacrylamide gel electrophoresis and silverstaining. With a computer-based image analysis system, we identified eight polypeptides which are present in both of the neoplastic cell lines, but absent from all five of the cultures of non-neoplastic breast cells. The eight polypeptides are not unique to cells cultured from neoplastic breast, because they are also found in cells cultured from non-breast tissues, both neoplastic and non-neoplastic. Two of the eight polypeptides ( M_r 25,000/pI 4.4 and M_r 31,000/pI 5.5) are present in the patterns of whole tissue samples from infiltrating ductal carcinomas and absent in most normal breast tissue.     

Histopathologic and dietary prognostic factors for canine mammary carcinoma

Summary Histologic and dietary prognostic factors for survival following naturally occurring breast cancer were studied for 145 pet dogs. Information was collected from the dog's owner and veterinarian regarding medical and reproductive history, nutritional status, treatment, tumor recurrence, and length of survival. The usual intake of all dog and table foods consumed 1 year prior to diagnosis was obtained using a validated quantitative food frequency questionnaire. A histologic malignancy score was derived based on 7 histopathologic criteria. The mean age of the dogs was 10.4 ± 2.5 years; 37% had been ovariohysterectomized prior to diagnosis. Product-limit estimates of survival indicated that 6 factors, namely body conformation 1 year prior to diagnosis (p = 0.03), histologic tumor type (p = 0.004), histologic malignancy score (p = 0.02), histologic invasion (p = 0.002), tumor recurrence (p<0.0001), and completeness of surgery (p = 0.01) were of prognostic significance. In addition, when dogs were characterized by the percent of total calories they derived from fat and protein, the median survival time for dogs in the low fat group (<39%) with protein >27%, 23–27%, and <23% was 3 years, 1.2 years, and 6 months, respectively (p = 0.008). For dogs in the high fat group (39%), there was no difference in survival for the different intake levels of dietary protein (p = 0.84). When these data were fitted to a proportional hazards model, recurrence, histologic score, tumor type, percent of calories derived from protein, fat group, and a protein-fat group interaction term were statistically significant. Predicted 1 year survival for dogs on a low fat diet with 15%, 25%, and 35% of total calories derived from protein was 17%, 69%, and 93%, respectively.