The results of radiotherapy for brainstem tumors

Objective: This analysis was performed to examine the outcome of adult and pediatric patients with brainstem tumors. Methods and materials: Forty patients with brainstem glioma were evaluated retrospectively. Included were 24 females and 16 males ranging in age from 3 to 81 years (median, 29.5 years). These patients were treated with various combinations of surgery, chemotherapy, and ratiotherapy (RT). The length of follow-up in survivors ranged from 0.6 to 20 years (median: 3.2 years, mean: 6 years). Survival rates were calculated with the Kaplan Meier method and differences between survival curves were calculated using the log-rank test. Results: The overall 2 and 5-year survival rates were 44% and 34%, respectively. The median survival time was 19 months. The 5-year survival rate was 54% for patients with tumors outside the pons compared to 21% for those with tumors involving the pons (p=0.04). The 5-year survival rate was 59% for patients with exophytic tumors as compared to 23% for those with intrinsic tumors (p=0.05). Patients undergoing subtotal resection had a 5-year survival rate of 53% compared to 28% for those having only a biopsy or no surgical intervention (p=0.04). None of the other potential prognostic or treatment related factors evaluated [patient age, tumor grade, tumor histology, radiotherapy parameters (including BID fractionation, 3-D treatment planning, or the use of doses > 55 Gy), or the administration of adjuvant chemotherapy] evaluated were associated with patient survival. Conclusions: Brainstem gliomas generally occur in younger individuals. The survival rates were better for patients with exophytic tumors, those involving sites other than the pons, and tumors amenable to subtotal resection. Improvements in the outcome of patients with brainstem gliomas will require new therapeutic approaches.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Mechanism of action of lonidamine in the 9L brain tumor model involves inhibition of lactate efflux and intracellular acidification

Malignant gliomas have been associated with a high rate of glycolytic activity which is believed necessary to sustain cellular function and integrity. Since lonidamine (LND) is believed to reduce tumor glucose utilization by inhibition of the mitochondrially-bound glycolytic enzyme hexokinase (HK), ³¹P magnetic resonance spectroscopy (MRS) was used to noninvasively follow the effects of LND on both tumor pH and the high-energy phosphate metabolites; ATP, phosphocreatine (PCr) and inorganic phosphate (P_i) in subcutaneous rat 9L gliosarcomas. ³¹P tumor spectra acquired in 5 min intervals pre- and post LND administration of 50 and 100 mg/kg, i.p. revealed an acidotic pH shift of – 0.25 and – 0.45 pH units, respectively within 30 min post administration. The ATP/P_i ratio of 9L tumors decreased to 40% of control and P_i levels increased to 280% of control over a 3 hr period. LND exerted no effect on tumor blood flow and mean arterial blood pressure. Brain and muscle metabolite levels and pH were also unaffected by LND. In vitro measurements of cultured 9L tumor cell intra- and extracellular lactate, pentose phosphate pathway (PPP) and hexokinase (HK) activities suggest that the mode of action of LND involves inhibition of lactate efflux and intracellular acidification. The selective reduction of tumor energy metabolites and pH by LND may be exploitable for sensitizing gliomas to radiation, chemotherapy or hyperthermia.     

宫颈病变液基细胞学筛查与组织病理学对照观察

目的　探讨液基薄层细胞学(ThinPrepCytologyTest, TCT)技术在妇科门诊人群宫颈病变筛查的准确性。方法　回顾性分析10 980例TCT,与组织学对比观察。结果　　TCTLSIL以上阳性率45. 7% ( 373 /817),组织学检查阳性率50. 1% ( 409 /817 ),两者统计学比较无显著性差异(P>0. 05 )。TCT诊断符合率LSIL75. 8% (191 /252),HSIL98. 1% (101 /103),SCC90. 9% (10 /11),AC85. 7% (6 /7)。鳞状上皮内病变诊断符合率HSIL与LSIL统计学比较有显著性差异(P<0. 01)。结论　液基细胞学检查是宫颈癌早期筛查的有效手段,加强制片技术及诊断质量控制对提高诊断的准确性有重要意义。     

The effect of family status and schizotypy on electrophysiologic measures of attention and semantic processing.

BACKGROUND: Disturbances in both attention and language are central to the phenomenology of the schizophrenia spectrum disorders. The purpose of this study was to investigate the relative contributions of two factors, family status and schizotypy, on electrophysiologic measures of attention and semantic processing in family members of individuals with schizophrenia. METHODS: Fifteen first-degree relatives of individuals with schizophrenia and 15 comparison subject controls participated in diagnostic evaluations, an assessment of schizotypy, and two event-related potential (ERP) paradigms. The first paradigm was an auditory P300 "oddball" task designed to assess attentional functioning. The second was an N400 sentence paradigm particularly sensitive to language processing. RESULTS: Both relatives and individuals higher in schizotypy, but not their respective comparison groups, showed reductions in P300 amplitude. In the N400 paradigm, individuals higher in schizotypy, but not relatives, showed a reduced N400 effect. There were no differences in latency for either group on either component. CONCLUSIONS: The results suggest that both family status and schizotypal presentation independently contribute to disturbances in electrophysiologic measures sensitive to attention and language. Whereas higher levels of schizotypy appear to be associated with disturbances in both attention and language processing, family membership appears to place individuals at risk for attentional deficits alone.     

Floating gallbladder: a questionable prelude to torsion: a case report

A 55-year-old woman had recurrent bouts of low substernal and epigastric pain radiating into the interscapular region. A hepatobiliary scan initially showed what was believed to be a dilated common bile duct and nonvisualization of the gallbladder. A delayed image obtained after having the patient move about revealed the presence of a filled gallbladder and normal common bile duct. The combination of recurrent pain with this scintigraphic picture may be representative of a floating gallbladder or an incomplete torsion with spontaneous detorsion. This case is presented to describe the scintigraphic appearance of a mobile gallbladder that may be prone to volvulus and to emphasize the importance of obtaining decubitus or oblique views at the end of a hepatobiliary study in selected cases of unusual findings.