Tumor antigenicity and the immune system in gynecological cancer: a review

A review of tumor immunology with particular emphasis on three gynecological malignancies, gestational trophoblastic disease, uterine cervical carcinoma, and ovarian carcinoma. Commentary includes the immune reactive cells and their functions as determined by in vitro and in vivo tests; serum and tissue antigen markers; and effects on the immune response of ionizing radiation, surgery, and chemotherapy.     

Modulation of tissue immunogenicity by organ culture. Comparison of adult islets and fetal pancreas

Uncultured mouse islet allografts (BALB/c to CBA) are rejected 2 to 4 weeks after transplantation. Allografts, cultured in 95% O2 and 5% CO2 for 7 days before transplantation, show no sign of rejection up to 3 months post-transplantation. However, the cultured allografts are rejected if the CBA recipient is given an i.v. injection of 10(5) peritoneal cells at the time of transplantation. Organ culture of BALB/c fetal pancreas (16 to 17 days gestation) under the same conditions failed to prevent allograft rejection. The immunogenicity of fetal pancreas is reduced if this tissue is cultured in 95% O2 and 5% CO2 for 17 days before transplantation.     

Maximizing worksite survey response rates through community organization strategies and multiple contacts

BACKGROUND. Worksites are natural settings for health promotion. In many cases, the effectiveness of such interventions is appraised by surveying employees to assess worksite-wide changes in the targeted behavior. Little attention has been paid to increasing worksite survey response rates. One way is to utilize community organization strategies, which involve enlisting the individuals within a group to work together with researchers to affect the social environment. METHODS. Community organization strategies and multiple contacts were used to obtain responses from employees in five worksites involved in a smoking cessation project. Employee Advisory Board members in each worksite reviewed, adapted, and revised the survey distribution method, the messages that accompanied the survey, and the survey content. Three major survey waves were undertaken: a worksite effort, a home mailing (in the pilot worksite only), and a telephone call to nonrespondents. RESULTS. Response rates to a worksite-wide survey in one worksite the first year and four additional worksites the next year yielded 99.3% and 98.4% response rates, respectively. In the pilot worksite, 273 employees were eligible for the survey with 366 eligible employees in the four other worksites. Chi-square or analysis of variance computations were used, as appropriate, to test for differences in characteristics of respondents in the various data collection waves. DISCUSSION. These results suggest that there may be merit in adapting such community organization intervention methods for research applications.     

Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys.

kappa-Opioid agonists may functionally antagonize some behavioral effects of cocaine, but the role of mixed kappa/mu receptor activity is unclear. The effects of three mixed kappa/mu agonists (MCL-101, (-)cyclorphan, and Mr2034) and one kappa-selective agonist (enadoline) on cocaine self-administration and cocaine discrimination were compared in rhesus monkeys. Acute treatment with all kappa agonists dose dependently reduced cocaine-maintained responding and produced a downward shift in the cocaine self-administration dose-effect curve (0.001-0.32 mg/kg/inj, i.v.). During 7 days of chronic treatment, (-)cyclorphan (0.0032-0.032 mg/kg/h) and MCL-101 (0.0032-0.032 mg/kg/h) each dose dependently reduced cocaine self-administration maintained by a dose near the peak of the cocaine self-administration dose-effect curve. MCL-101 (0.032 mg/kg/h) produced selective and sustained decreases in cocaine self-administration, whereas (-)cyclorphan (0.032 mg/kg/h) had selective but transient effects. In addition, these mixed kappa/mu agonists produced fewer side effects (some salivation) than the kappa-selective agonist (sedation, salivation, emesis). However, none of these kappa agonists substituted for or antagonized cocaine's discriminative stimulus effects in monkeys trained to discriminate cocaine (0.4 mg/kg, i.m.) from saline. Thus, kappa and mixed kappa/mu-opioid agonists may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects. Mixed kappa/mu agonists appear to offer some advantages over selective kappa agonists as potential treatments for cocaine abuse.     

Minority recruitment in hereditary breast cancer research.

Although recruitment of ethnic and racial minorities in medical research has been evaluated in several studies, much less is known about the methods used to recruit these populations to participate in cancer genetics research. This report reviews the resources that have been used to identify and recruit ethnic and racial minorities to participate in hereditary breast cancer research. Overall, hospital-based resources were used most often to identify potential subjects, and active recruitment methods were used most frequently to enroll eligible subjects. This review suggests that there appears to be a finite number of resources and strategies to identify and recruit potential subjects to participate in cancer genetics research; however, options for improving awareness about cancer genetics research among ethnic and racial minorities have not been extensively evaluated. To study ethnic and racial minority participation in cancer genetics research, stronger evaluation components will need to be integrated into research methods. Both observational and experimental studies are needed to determine resources that are most effective for identifying potential subjects who are ethnic and racial minorities and to evaluate the effects of different recruitment strategies on enrollment decisions among these populations.     

Isoflavone genistein inhibits the initiation and promotion of two-stage skin carcinogenesis in mice

Isoflavone genistein is a specific inhibitor of protein tyrosine kinase (PTK) and has been shown to have a variety of anticancer activities in cultured cells and animal models. We report here that genistein significantly inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-promoted skin tumorigenesis in a two-stage carcinogenesis model. In an initiation study, 10 micromol genistein was applied daily to female SENCAR mouse skin for 1 week, followed by initiation with 10 nmol DMBA. Mice were then treated with twice weekly 4 microg TPA. Genistein was shown to reduce tumor incidence and multiplicity in DMBA-initiated skin tumors by approximately 20 (P < 0.05) and 50% (P < 0.01), respectively. Two promotion studies were conducted using CD-1 and SENCAR mice. In experiment 1, CD-1 mice were initiated with 100 nmol DMBA and followed by a twice weekly regimen of 1 and 5 micromol genistein/4 microg TPA. In experiment 2, SENCAR mice were initiated with 10 nmol DMBA and followed by a regimen of 5, 10 and 20 micromol genistein/2 microg TPA. Both studies consistently showed that genistein substantially inhibited TPA-promoted skin tumorigenesis by reducing the tumor multiplicity by approximately 60 and 75%, respectively (P < 0.01). However, the tumor incidence appeared to be less affected. Mechanistic studies showed that genistein inhibited DMBA-induced bulky DNA adduct formation and substantially suppressed TPA-stimulated H2O2 and inflammatory responses in mouse skin by >60% (P < 0.01). In contrast, genistein only exhibited a moderate inhibition of TPA-induced ornithine decarboxylase activity (P > 0.05). Our results suggest that genistein exerts its anti- initiational and anti-promotional effects on skin carcinogenesis probably through blockage of DNA adduct formation and inhibition of oxidative and inflammatory events in vivo.      

乳腺恶性淋巴瘤细针吸取细胞学诊断

目的讨论细针吸取细胞学诊断乳腺恶性淋巴瘤病例的细胞形态学特征，鉴别诊断和诊断价值。（方法）对7例患者的临床、病理及细胞学资料进行回顾性分析。（结果）在4918例乳腺肿瘤病例中，发现7例恶性淋巴瘤，占乳腺恶性肿瘤的1．08％（7／647）。7例均为非何杰金淋巴瘤，对照分析其细胞学、组织学及超微结构等形态学表现，证明细胞学结果是可靠的。（结论）细针吸取细胞学诊断乳腺恶性淋巴瘤具有安全、方便和可重复性等优点，诊断时需与良性淋巴组织增生、小细胞未分化癌和具有浆细胞样特征的腺癌鉴别。     

Initial response to portoenterostomy determines long-term outcome in patients with biliary atresia

PURPOSE: The aim of this study was to assess the efficacy of portoenterostomy in biliary atresia and determine factors that predict outcomes. METHODS: The outcomes after portoenterostomy for biliary atresia from 1976 to 1996 were graded into 3 defined groups: G (good, jaundice free); I (intermediate, progressive liver disease with liver transplant if needed after 3 years of age); P (poor, liver transplant or death at less than 3 years of age). RESULTS: Twenty-seven of 49 children (55%) who underwent portoenterostomy responded. Of these, 13 (26%) were jaundice free (G). Of 14 children (28%) in I, 6 underwent liver transplant after 3 years of age. Of 22 children (44.8%) in P, 14 (28%) died before 3 years and 8 underwent liver transplant before 3 years. Thus, 42% of the children in this series are surviving with native liver. Age at operation in P was significantly different compared with G. Preoperative values of bilirubin and alanine transaminase were comparable in the 3 groups. Postoperative values of bilirubin and alanine transaminase were lower in G and I compared with P Complications were significantly lower in group G. CONCLUSIONS: Portoenterostomy alone in biliary atresia is beneficial in 40% of cases. Factors associated with the outcome include age at operation, postoperative cholangitis, and change in values of bilirubin and alanine transaminase. A classification based on decline of bilirubin and enzyme levels 3 months after portoenterostomy is proposed to predict the long-term outcome of an individual case of biliary atresia. It is particularly relevant in the intermediate group in which timing of referral may preclude or compromise liver transplant.     

Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis

OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.