胃癌癌区动—静脉血及其癌组织胃泌素变化的研究

目的：临床观察胃癌癌区动－静脉血及其癌区组织、癌旁区粘膜和外周区正常粘膜中胃泌素的变化,探讨病人体内胃泌素变化的原因和意义。方法：采用放射免疫法测定２６例胃癌患者癌区动－静脉血及其癌区组织、癌旁区粘膜和外周区正常粘膜中胃泌素水平。结果：胃癌癌区静脉血中胃泌素水平显著高于癌区动脉血（Ｐ＜０．０５）。胃窦部癌癌旁粘膜中胃泌素水平显著高于癌区组织和外周区正常粘膜（Ｐ＜０．０１）,也显著高于胃体部癌癌旁区粘膜（Ｐ＜０．０１）。胃体部癌癌旁区粘膜中胃泌素水平显著高于癌区组织（Ｐ＜０．０５）。结论：胃癌组织能分泌和释放胃泌素,可能是导致静脉血中胃泌素水平升高的主要原因。癌旁区粘膜中胃泌素的增多可能在胃癌的发生发展中起重要作用。     

大肠癌病人外周血,肿瘤及癌旁粘膜中胃泌素,生长抑素水平的…

对４８例大肠癌病人外周血，肿瘤及癌旁粘膜匀浆中胃泌素，生长抑素水平的ＲＩＡ测定。结果表明：癌患者平均血清胃泌素水平显著高于对照组，肿瘤切除后明显下降；分组比较表明Ｄｕｋｅｓ Ｃ期和直肠癌病人平均ＳＧ水平显著高对照组；肿瘤及癌旁粘膜中胃泌素水平很低，无法测出     

结直肠癌患者手术前后血清唾液酸浓度的变化

为探讨结直肠癌患者手术前后血清唾液酸（Ｓｉａｌｉｃａｃｉｄ，ＳＡ）浓度的变化及临床意义，作者采用单一试剂比色法检测了４５例正常人和５３例结直肠癌患者的血清ＳＡ浓度。结果显示，结直肠癌组血清ＳＡ浓度显著高于正常对照组（Ｐ＜０．０１），且Ｄｕｋｅｓ′Ｃ组显著高于Ｄｕｋｅｓ′Ｂ组（Ｐ＜０．０５），Ｄｕｋｅｓ′Ｂ组显著高于Ｄｕｋｅｓ′Ａ组（Ｐ＜０．０５），根治性切除术后各组的血清ＳＡ均显著下降（Ｐ＜０．０５）。表明血清ＳＡ浓度可作为结直肠癌辅助诊断和评估疗效的指标之一。     

生长抑素 SMS201-995 对小鼠结肠腺癌肝转移瘤的实验研究

目的本研究观察生长抑素衍生物ＳＭＳ２０１┐９９５对ＢＡＬＢ／ｃ小鼠结肠腺癌（ＣＴ２６）肝转移瘤细胞周期的影响，检测血清ＣＥＡ水平的变化，并观察小鼠生存期的改变。方法采用流式细胞术。结果与对照组相比，ＳＭＳ２０１┐９９５治疗组的瘤细胞增殖指数和Ｓ期细胞百分比明显降低（Ｐ＜０．０１），而Ｇ０／Ｇ１期细胞百分比则明显增加（Ｐ＜０．０１）。治疗组血清ＣＥＡ水平较对照组显著降低（Ｐ＜０．０５），生存期明显延长。治疗组细胞增殖指数，Ｓ期和Ｇ０／Ｇ１期细胞百分比与血清ＣＥＡ的变化密切相关（相关系数与Ｐ值分别为：ｒ＝０．６６７７，Ｐ＜０．０５；ｒ＝０．７１７０，Ｐ＜０．０１；ｒ＝－０．６７０３，Ｐ＜０．０５）。结论ＳＭＳ２０１┐９９５对结肠腺癌（ＣＴ２６）肝转移性肿瘤的生长具有一定的抑制作用。     

结直肠肿瘤细胞核形态计量和PCNA相对含量测定及其意义

应用图像分析技术测定６２例结直肠癌、１０例腺瘤、２７例癌旁粘膜及８例正常大肠粘膜细胞核的形态参数和ＰＣＮＡ相对含量。结果显示：腺瘤及腺癌的核面积（１１８９８±３８６６，１１７３６±３９５９μｍ）、核周长（５４２２±１０８４，４８１７±１０４３μｍ）及核长径（２０００±５８０，１６５２±３１８μｍ）大于正常粘膜及癌旁粘膜（Ｐ＜００１或Ｐ＜００５）。腺瘤的核形状因子（２０２±０３３）大于正常粘膜及癌旁粘膜，也大于结直肠癌（Ｐ＜００５、Ｐ＜００１及Ｐ＜００１）。乳头状腺癌的核形状因子大于除高分化腺癌以外其它组织学类型的结直肠癌（Ｐ＜００１或Ｐ＜００５）。癌细胞核形状因子数值大的病人五年生存率高（Ｐ＜００１）。ＰＣＮＡ相对含量与结直肠癌的生物学行为和预后无明显关系（（Ｐ＞００５）。结果提示：结直肠癌细胞核的形状因子可作为估计结直肠癌病人预后的指标之一，核形状因子数值大者，反映结直肠癌的分化较好，恶性程度较低。     

大肠癌病人血清胃泌素水平变化的临床研究

目的 探讨血清胃泌素与大肠癌的关系及其临床意义。方法 用放免法测定３９例行根治术的大肠癌病人空腹血清胃泌素水平。结果 大肠癌病人血清胃泌素水平明显高于对照组（Ｐ〈０．０５）；高分化腺癌组术前血清胃泌素水平显示高于对照组及中、低分化腺癌组（Ｐ〈０．０５），Ｄｕｋｅｓ’Ａ期病人根治术后其胃泌素水平较术前明显下降（Ｐ〈０．０５）。结论 血清胃泌素可能对大肠癌细胞有内分泌促生长作用；血清胃泌素水平测定可作     

大肠癌中DCC基因201密码子点突变的研究

目的：探寻结直肠癌缺陷基因（ＤＣＣ基因）２０１密码子在大肠癌中的突变规律。方法：采用等位基因特异性ＰＣＲＡＳ－ＰＧＲ结合ＳａｌⅠ酶切方法检测３５例大肠癌组织及配对的癌旁粘膜ＤＣＣ基因２０１密友子突变情况。结果：ＤＣＣ基因２０１密码子纯合突变率大肠癌（４０％）显高于癌旁粘膜（２．８％）,（Ｐ〈０．０５）。且与肿瘤侵袭深度、Ｄｕｋｅｓ分期相关,至少有１７例（４９％）大肠癌与相应癌旁粘膜相比增获一个密     

恶性肿瘤患者血液中LPO,SOD,GSH—PX临床价值的初步分析

本文对１０９例恶性肿瘤及５０例正常对照者血浆脂质过氧化物（ＬＰＯ）、全血超氧化物歧化酶（ＳＯＤ）及谷胱甘肽过氧化物酶（ＧＳＨ—ＰＸ）进行测定，结果显示：结肠癌的ＬＰＯ值最高；胃癌的ＳＯＤ值最高；骨癌的ＧＳＨ—ＰＸ值最高。各肿瘤组之间，肿瘤组与正常对照组之间两两比较，ｑ检验，多数组间的Ｐ＜０．０１或ＰＭ０．０５，ＳＯＤ与ＬＰＯ呈负相关，ｒ＝０．１７，Ｐ＜０．０５。经判别分析，在Ｆ＝３水平上选入ＬＰＯ、ＳＯＤ、ＧＳＨ—ＰＸ三因素与判别癌与非癌有关，符合率达８０．５％，特异性９０％，灵敏性７６．１％，可供探讨肿瘤与自由基的关系及临床诊断作参考。     

nm23基因在食管癌中表达的免疫组化研究

目的研究ｎｍ２３基因表达与食管癌生物学行为和预后的关系。方法应用免疫组织化学ＳＰ法检测７６例食管鳞状细胞癌手术标本中ｎｍ２３表达。结果食管癌原发灶癌组织中ｎｍ２３表达阳性率８１．６％，癌旁形态学正常食管粘膜ｎｍ２３阳性率３６．８％，差异具有显著性意义（Ｐ＜０．００１）；食管癌ｎｍ２３高表达者的区域淋巴结转移发生率（５８．２％）明显高于低表达者（２２．２％，Ｐ＜０．００５）；ｎｍ２３表达水平与癌组织浸润食管深度及食管癌ＴＮＭ分期呈正相关，统计学均具有显著性意义（分别为Ｐ＜０．０５、Ｐ＜０．０２）；ｎｍ２３低表达的患者术后三年和五年生存率分别为６０．０％和５１．６％，显著高于ｎｍ２３高表达者（３８．７％和２２．６％），Ｐ＜０．０５和Ｐ＜０．０１。结论ｎｍ２３基因过度表达与食管鳞状细胞癌的浸润及淋巴结转移有关，是预后不良的指标     

大肠癌亲和酶标法检测雌孕激素受体及临床生物学意义

目的探讨雌孕激素受体与结直肠癌病理、临床及生物学行为的关系。方法应用免疫组织化学的亲和酶标法检测５３例结直肠癌的雌激素受体和孕激素受体。结果雌孕激素受体总阳性率为６０％（３２／５３）；女性和男性阳性率分别为７５％（２１／２８）和４４％（１１／２５），差异有显著意义（Ｐ＜０．０５）。管状乳头状腺癌受体阳性率为７０％，高于印戒细胞和粘液腺癌３８％（Ｐ＜０．０５）；ＤｕｋｅｓＢ期受体阳性率为７５％，高于Ｄ期３３％（Ｐ＜０．０５）；淋巴无转移者受体阳性率为８５％，高于有转移者４５％（Ｐ＜０．０５）。肿瘤体积＜５ｃｍ３者受体阳性率为７１％，高于≥５ｃｍ３者３９％（Ｐ＜０．０５）。直肠癌受体阳性率为７１％，高于结肠癌３３％（Ｐ＜０．０５）。高分化癌受体阳性率为７８％，高于低分化癌３５％（Ｐ＜０．０５）。结论女性大肠癌发病与受体关系密切；受体作用失常参与大肠癌发病始于较早期阶段；直肠癌发病与受体密度增高关系更为密切。     

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

Trends in Breast Cancer Mortality, Incidence, and Survival, and Mammographic screening in Tuscany, Italy

Objective: The study describes breast cancer mortality trends in Tuscany (period 1970–97), comparing Florence with the rest of Tuscany (Florence excluded), and, for Florence, incidence (period 1985–94) and survival (1985–86 versus 1991–92) trends, taking into account the diffusion of screening. Methods: Mortality and incidence rates, age-adjusted on the European population, and 95% confidence intervals (95% CI). Five-year relative survival rates and estimates of risk of dying provided by the Cox model. Results: Mammographic screening, started at the beginning of the 1970s in some municipalities, largely involved the Florence area after 1990 (mammograms/years: from 8000–9000 to 28,000–29,000, respectively, before and after 1990). In the same period no population-based screenings were ongoing in the rest of Tuscany. A significant mortality drop was observed in Tuscany (–3.7%/year), starting at the beginning of the 1990s and observed for ages 74 (especially ages 40–49: –11.2%/year). The drop was similar in Florence and in the rest of Tuscany. In ages 50–69, incidence, increasing between 1985–87 and 1988–90 (+6.5%), rose sharply in 1991–94 (+17.0%); it was stable in other ages. Local disease increased more markedly in ages 50–69 (globally: +88.3%), but also in other ages (+20–30%). Regional and metastatic cancers decreased. A significantly better 5-year survival was observed among cases diagnosed in 1991–92, persisting after adjustment by extent of disease. Conclusion: Even if the causes of breast cancer mortality trends are not easy to clarify in an observational study, our data suggest that the drop in mortality observed in Tuscany at the beginning of the 1990s could be largely explained by both earlier detection, outside of an organized screening program, and by better treatments. The increase in incidence and the shift in stage distribution that occurred before the enlargement of the screening area and in age groups not involved in the program, supports the role of a `spontaneous' widespread earlier detection. The better survival of the period 1991–92, only partly explained by the shift in stage at diagnosis, indirectly supports the role of improvement in therapy.     

Strain and sex differences in N-nitrosohexamethyleneimine carcinogenesis in NZB, NZC, NZO, and NZY mice

The carcinogenic activity of N-nitrosohexamethyleneimine [(NHEX) CAS: 932-83-2; hexahydro-1-nitroso-1H-azepine] was studied in male and female mice of the four inbred strains NZB/BlGd, NZC/BlGd, NZO/BlGd, and NZY/BlGd. A total of 158 mice received NHEX treatment; 1,338 untreated controls were used, all kept under identical laboratory conditions for their natural life-spans. Beginning at age 50 days a 1.56-mM NHEX solution (200 mg/liter) was given instead of drinking water for 8 weeks, which resulted in nearly the same total dosage of 0.7 +/- 0.04 g or 5.7 +/- 0.2 mmol NHEX/kg body weight in both sexes of all four strains. In both sexes of all four strains the main types of tumors after NHEX treatment were squamous papillomas and carcinomas of the esophagus, squamous stomach, and oropharynx and hepatocellular carcinomas. Tumors of the hepatic bile ducts, glandular stomach, and lung and malignant lymphomas were also induced by NHEX, but these tumors had a predilection for certain strains only. The incidences of other tumors characteristic of the untreated mice in each particular strain, such as tumors of the ovary in NZC, tumors of the breast in NZY, and tumors of the duodenum in NZO, were not increased significantly by NHEX treatment. The incidence of main tumor types in NHEX-treated mice varied greatly between strains, e.g., esophageal papillomas and carcinomas in 81% of male NZC versus 32% in male NZB mice. Some marked sex differences also emerged in NHEX-treated animals, e.g., the occurrence of liver angiosarcomas only in males of three strains and the 53% incidence of hepatocellular tumors in male NZY mice compared to the absence of liver tumors in female NZY mice.     

Diabetes,diabetes treatment,and mammographic density in Danish Diet,Cancer, and Health cohort

Purpose

We examined whether diabetes and diabetes treatment are associated with MD in a cohort study of Danish women above age of 50 years.

Methods

Study cohort consisted of 5,644 women (4,500 postmenopausal) who participated in the Danish Diet, Cancer, and Health cohort (1993–1997) and subsequently attended mammographic screening in Copenhagen (1993–2001). We used MD assessed at the first screening after the cohort entry, defined as mixed/dense or fatty. Diabetes diagnoses and diabetes treatments (diet, insulin, or oral antidiabetic agents) were self-reported at the time of recruitment (1993–1997). The association between MD and diabetes was analyzed by logistic regression adjusted for potential confounders. Effect modification by menopausal status and body mass index (BMI) was performed by introducing an interaction term into the model and tested by Wald test.

Results

Of 5,644 women with mean age of 56 years, 137 (2.4%) had diabetes and 3,180 (56.3%) had mixed/dense breasts. Having diabetes was significantly inversely associated with having mixed/dense breasts, in both, the crude model (odds ratio; 95% confidence interval: 0.33; 0.23–0.48), and after adjustment for adiposity and other risk factors (0.61; 0.40–0.92). Similar inverse associations were observed for 44 women who controlled diabetes by diet only and did not receive any medication (0.56; 0.27–1.14), and 62 who took oral antidiabetic agents only for diabetes (0.59; 0.32–1.09), while women taking insulin had increased odds of mixed/dense breasts (2.08; 0.68–6.35). There was no effect modification of these associations by menopausal status or BMI.

Conclusions

Having diabetes controlled by diet or oral antidiabetic agents is associated with a decrease in MD, whereas taking insulin is associated with an increase in MD.

     

Consumption of alcohol,coffee, and tobacco,and gastric cancer in Spain

A case-control study on gastric cancer was carried out between 1987 and 1989 in four regions of Spain. Three hundred and fifty-four cases of histologically confirmed adenocarcinoma were included (235 men and 119 women). For each case, a control was selected, matched by sex, age, and area of residence, from the same hospital as the case. No association was observed with smoking, nor with the consumption of coffee or tea. The usual consumption of alcohol was associated with gastric cancer in men (odds ratio = 1.54, 95 percent confidence interval = 1.03–2.31), but there was no dose-response relationship. No association was observed in women. All estimations were carried out taking into account the effect of the dietary factors associated with gastric cancer. In accordance with previous evidence, the association observed between gastric cancer and alcohol appears not to be causal.Drs Agudo and González are with the Unit of Epidemiology, Hospital de Mataró, Mataró, Spain. Dr Marcos is with the Department of Preventive Medicine, Hospital Clínico, Zaragoza, Spain. Dr Sanz is with the Department of Pathology, Hospital del INSALUD, Soria, Spain. Dr Saigi is with the Department of Oncology, Hospital General de Granollers, Granollers, Spain. Dr Verge is with the Department of Surgery, Hospital de Terrassa, Terrassa, Spain. Dr Boleda is with the Department of Oncology, Hospital S. Camil, Sant Pere de Riba, Sapin. Dr Ortego is with the Department of Pathology, Hospital Clínico, Zaragoza, Spain. Address correspondence to Dr Agudo, Unit of Epidemiology, Hospital de Mataró, c. Hospital 31, 08301 Mataró, Spain. This study received financial support from the Health Research Fund (FIS) of the Spanish Ministry of Health (Financial Aid for Research exp. 87/1703, exp. 89/0018 and exp. 89/0743) and from the International Agency for Research on Cancer (Collaborative Research Agreement AEP/88/02).