Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE: This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS: Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS: With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION: WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.     

High glucose inhibits glucose uptake in renal proximal tubule cells by oxidative stress and protein kinase C

BACKGROUND: High glucose has been considered to play an important role in alteration of renal proximal tubule transporter's activity. This study examined the mechanism by which high glucose modulates alpha-methyl-D-glucopyranoside (alpha-MG) uptake in primary cultured rabbit renal proximal tubule cells (PTCs). METHODS: PTCs were incubated with 25 mmol/L glucose alone or combined with taurine, ascorbic acid, catalase, staurosporine, and bisindolylmaleimide I. Then alpha-MG uptake and lipid peroxide (LPO) formation were examined. RESULTS: Twenty-five mmol/L glucose from four hours, but not 25 mmol/L mannitol, inhibited alpha-MG uptake by 23% compared with 5 mmol/L glucose (control). In the study to examine the relationship of oxidative stress in the high-glucose-induced inhibition of alpha-MG uptake, 25 mmol/L glucose significantly increased LPO by 27% compared with control. However, 10 mmol/L glucose did not affect alpha-MG uptake and LPO formation. Taurine (2 mmol/L), ascorbic acid (1 mmol/L), endogenous antioxidants, or catalase (600 U/mL) significantly blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In the experiment to examine the effects of protein kinase C on LPO formation, 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 ng/mL) increased LPO formation, and staurosporine (10(-7) mol/L) and bisindolylmaleimide I (10(-6) mol/L) totally blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In addition, taurine reduced TPA-induced increase of LPO formation and inhibition of alpha-MG uptake. CONCLUSION: High glucose induces, in part, the inhibition of alpha-MG uptake through LPO formation, and activation of protein kinase C may play a role in high-glucose-induced LPO formation in the primary cultured rabbit renal PTCs.     

细胞凋亡及增殖细胞核抗原在肝癌组织中的表达及意义

目的探讨经肝动脉化疗栓塞(TACE)后肝癌细胞中增殖细胞核抗原(PCNA)广凋亡细胞比值与肝细胞肝癌分化程度的关系。方法应用原位末端标记法(TUNEL)及免疫组化双染色技术，对60例肝细胞肝癌石蜡包埋组织进行检测。结果不同分化程度癌组织中细胞凋亡和PCNA的阳性率不同。分化程度高，细胞凋亡阳性率高、PCNA阳性率偏低；分化程度低，细胞凋亡阳性率偏低、PCNA阳性率高。随分化程度的降低，PCNA广凋亡细胞的比值显著增加，两者有相关性。结论PCNA/凋亡细胞的比值可作为评估肝细胞肝癌分化程度的指标。     

中药脑肺康对地鼠实验性肺气肿及肺动脉高压的防治作用

目的 观察中药肺康对缺氧性肺动脉高压和肺气肿的防治效果并探讨其作用机制。方法 以弹性蛋白酶溶液滴注入金黄地鼠气管内,正常饲养３０ｄ后,常压下缺氧１５ｄ,分别设立中药脑肺康预防组、治疗组、肺气肿＋缺氧组及正常对照组。于处死动物前,测量平均肺动脉压,取静脉血进行循环内皮细胞计数;处死后测量右心肥大指数,光镜下计数左侧肺支气管肺泡灌洗液内细胞总数,对右侧肺进行光镜图像分析。结果 中药脑肺康预防组和治疗３     

Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 ± 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 ± 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.     

参龙降压灵对自发性高血压大鼠血压及血浆ET、CGRP含量的影响

目的与方法本实验观察了中药制剂参龙降压灵对自发性高血压大鼠（ＳＨＲ）血压、血浆内皮素（ＥＴ）及降钙素基因相关肽（ＣＧＲＰ）含量及心室结构的影响,并与尼群地平（ｎｉｆｅｄｉｐｉｎ）及牛黄降压丸作对比。结果各给药组给药１－８周后血压均比ＳＨＲ对照组明显降低（Ｐ＜０.０５－０.０１）,给药６周后参龙降压灵大剂量组血压下降幅度最大,效果优于小剂量组及其他两给药组（Ｐ＜０．０５－０．０１）。各给药组心室结构各参数多有降低,虽无统计学意义（可能例数较少）,但已显示出心室肥厚逆转的趋势。各给药组ＳＨＲ血浆ＥＴ含量均有明显降低,ＣＧＲＰ含量升高（Ｐ＜０.０５－０.０１）,而大剂量参龙降压灵作用更显著,与Ｗｉｓｔａｒ正常组大鼠含量接近。结论参龙降压灵降低ＳＨＲ血压作用确实,有逆转心室肥厚趋势及调节血浆ＥＴ和ＣＧＲＰ含量的作用,且有一定的量效关系。     

Nutritional origins of insulin resistance: a rat model for diabetes-prone human populations

While there has been little success identifying the genetic bases of noninsulin-dependent (type-2) diabetes, current epidemiological data and animal models implicate fetal undernutrition in the development of type-2 diabetes. We examined the effects of fetal undernutrition on insulin responses and glucose tolerance in adulthood in genetically normal rats. Control rats were adequately nourished in utero and consumed nutritionally adequate (N) diets throughout life. Experimental rats (F1 generation) were undernourished in utero and consumed either N or high-energy, high-fat (HF) diets postweaning. The offspring of the experimental rats (F2 generation) received the respective diets of their parent. Body weights of experimental F1 rats at d 4 were 40% less than that of control pups, and they remained significantly smaller than controls throughout adulthood. The experimental F1 rats consuming N diets postweaning had a reduced insulin response (-30%) at 30-min postglucose challenge in adulthood (P > 0.05). However, their offspring (F2 generation) displayed a markedly elevated insulin response [+80% at 30 min (P < 0.05) and + 230% at 120 min (P < 0.001) postglucose challenge]. The insulin response of the F2 generation rats fed the high-energy, HF diet was even more pronounced [+130% at 30 min (P < 0.003) and + 250% at 120 min (P < 0.001) postglucose challenge]. Thus, undernourishment in utero produces striking insulin resistance in genetically normal, well-nourished second-generation rats.