Analysis of the P300/CBP-Associated Factor (PCAF) Gene in Astrocytic Tumors

The PCAF gene encodes the p300/CBP-Associated Factor (PCAF), a histone acetyltransferase, which regulates p53 by acetylation of Lys320 in the C-terminal portion of p53. While the p53 gene is one of the most frequently mutated tumor suppressor genes in human tumors, such mutations occur in only 30% of astrocytic tumors. Since PCAF can regulate p53 activity, abrogation of PCAF function by PCAF gene mutation could be an alternate mechanism to inactivate the p53 pathway in tumors lacking p53 mutations. To test this hypothesis, we determined the nucleotide sequence of the entire PCAF coding region in 37 astrocytic tumors (17 glioblastomas, 10 anaplastic astrocytomas, 7 low-grade astrocytomas, and 3 pilocytic astrocytomas). We detected two single-nucleotide alterations that represented non-deleterious polymorphisms (GAG > GAA Glu103Glu, AAT > AGT Asn386Ser) but no obvious functional mutations. Moreover, the frequency of the Asn386Ser allele that contained Ser386 in glioma patients was not statistically different from its frequency in individuals without disease, and no significant association was observed between the PCAF polymorphisms and the presence or absence of p53 mutations in the tumors. We conclude that the PCAF gene is not mutated during the development of the astrocytic tumors studied here.     

Brain stem auditory evoked potentials in medical coma

BAEPS are coming up as an important investigatory tool in the hands of present clinicians and have a diagnostic and prognostic significance. The present study was carried on 25 patients. BAEPS were recorded at the time of admission and analysed. Absent BAEPS were associated with high mortality. Abnormal BAEPS were seen in infective and CVA group. Followup BAEPS showed no change in those patients who died.     

Brainstem auditory evoked potentials in severe head injury

25 patients of severe head injury were taken in this study and their BAEPS recorded. Absolute peak latencies II, III, V were significantly delayed (P < .05). Interpeak latencies III– V and I– V were also significantly delayed (P < .01). Absent BAEPS were associated with worst prognosis.     

Cognitive impairments in breast cancer survivors treated with chemotherapy: a study based on event-related potentials

Cancer Chemotherapy and Pharmacology - Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective...     

Osseointegration of dental implants in patients with and without radiotherapy

Between 1987 and 1997, 275 dental implants were inserted in the mandibles of 63 patients with squamous cell carcinoma of the lower oropharyngeal level following a radical surgical procedure. Thirty-five of these patients had been preirradiated with a complete dose of 60 Gy. In a retrospective analysis we have reviewed the data of these patients for age, sex, localization of the implants, irradiation, interval of implantation and interval of the abutment operation. Thus far, the median follow-up time is 65 months. The 5-year success rate for all implants was 97.9%. We found that radiotherapy, age, sex, localization of implantation or the interval between the end of the tumor therapy and the time of implantation did not have any significant influence on osseointegration or loss of osseointegration. Only the time interval between implantation and the abutment operation was recorded to be of any great significance (p = 0.0001). No augmentation in the osteoradionecrosis rate could be recorded after dental implantation (1.6%), which leads us to conclude that radiotherapy (60 Gy) in patients with head and neck cancers should not be regarded as a contraindication for dental implantation.     

Evaluation of desmethylmisonidazole-induced neurotoxicity in the rat using brainstem auditory evoked potentials

Brainstem auditory evoked responses (BAEPs) and a scale that evaluates clinical signs of neurotoxicity were used to measure the onset of neurotoxic effects seen in rats after chronic injection of 400 mg/kg/day of the radiosensitizer desmethylmisonidazole (DMM) for 5 days/week for 7 weeks. A significant neurotoxic effect was indicated by increases in the latencies of peaks 4 and 5 of the BAEP after the 24th injection of DMM; clinical signs of neurotoxicity were observed after the 30th injection. Histologic examination of brainstems from rats sacrificed after selected number of injections during treatment showed that the onset of lesions in the brainstem was gradual but not extensive. Pentobarbital used as an anesthetic agent had no effect on the induction of neurotoxicity.     

300 mg/m2 carboplatin (Cb), adriamycin (A) cyclophosphamide (C) (CACb-300) combination in advanced ovarian carcinoma: a feasibility study

Summary Carboplatin (Cb) is an active drug in ovarian carcinoma that has fewer visceral side effects than cisplatin (CDDP) but higher myelotoxicity, which makes it difficult to combine at efficient doses with other myelotoxic drugs. In a preliminary study in advanced ovarian carcinoma, Rosso et al. [4] showed the maximum tolerated dose of Cb given in combination with cyclophosphamide (C) and adriamycin (A) to be 200 mg/m². Since the efficacy of Cb may be dose-dependent, as is that of CDDP, we started a feasibility study of a CACb-300 regimen, that is, using Cb at 300 mg/m² with lower C and A doses. Our data shows that the CACb-300 combination can safely be given in previously untreated patients for at least six 28-day cycles.     

P300／CBP 在恶性肿瘤中的研究进展

P300/CBP是组蛋白乙酰转移酶（ HAT）中重要的大分子蛋白之一,P300/CBP具有高度的同源性,虽然由不同的基因编码,但因其有相近的氨基酸排序和功能,而且又属于同一类的蛋白质,所以经常把它们写为P300/CBP。 P300/CBP参与了很多种转录因子的激活,它本身也存在着乙酰转移酶活性,能够乙酰化4种核心组蛋白和多种转录因子。越来越多的研究证实P300/CBP的变异与人类多种疾病,糖尿病,炎症、心脏病,特别是肿瘤的发病相关,P300/CBP在肿瘤中也与一些通路有相关性,而这些通路在肿瘤中扮演着不同的角色。 P300/CBP虽然通常被看做是肿瘤抑制因子,但是在不同的肿瘤中P300/CBP也起着不同的作用,本文主要介绍了P300/CBP与一些实体肿瘤发病相关的基因之间的作用以及有关的转录因子和相关的转导通路。     

Biodistribution and dosimetry of (99m)Tc-depreotide (P829) in patients suffering from breast carcinoma

OBJECTIVE: This paper reports on the biodistribution and dosimetry of (99m)Tc-depreotide in patients. METHODS: Whole body planar images were acquired 30 minutes, 1, 2, 4, 9, and 24 hours after intravenous injection of 555-740MBq (99m)Tc-depreotide in 5 breast cancer patients. Urine was collected up to 24 hours after injection, allowing for a calculation of renal clearance and an interpretation of whole body clearance. Time activity curves were generated for the thyroid, lungs, liver, spleen, kidneys, colon, thoracic vertebrae/sternum, and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest (ROIs). The Medical Internal Radiation Dose (MIRD) formulation was applied to calculate the absorbed radiation dose for various organs. RESULTS: The whole body images show most of the activity distributed in the liver, spleen, and kidneys. Nearly all excretion of activity occurred by the renal system, and hepatobiliary excretion was negligible. Elimination of administered activity occurred predominantly through physical decay. The mean cumulative measured urinary excretion at 24 hours postinjection was 14.0% (standard deviation; 11.8%) of the administered activity. The highest absorbed dose was received by the kidneys, thyroid, and spleen. The average effective dose was estimated to be 1.15E-02mSv/MBq (standard deviation; 1.41E-03mSv/MBq). CONCLUSION: The biodistribution of (99m)Tc-depreotide demonstrated low lung and myocardial uptake allowing early imaging of the supradiaphragmatic region and this with a dosimetry favorable for clinical whole body and single photon emission computed tomography (SPECT) imaging.     

Phase II trial of etoposide (V), adriamycin (A), and cisplatinum (P) in patients with metastatic gastric cancer

The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide. Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. Hematologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes.     

Maturation of cochlea,auditory nerve and brainstem as observed by auditory brainstem evoked potentials in human infants and children

Myelination of the 8th nerve and Maturation of the brainstem have a direct relationship to the function of hearing and speech development. If disease conditions affect the pathway daring early childhood, damage results in deficit of auditory and speech skills. We have studied this by employing auditory brainstem evoked potentials in 11 children (1 month to 2 years). From 1 month to 6 months, there is no evidence of significant myelination at ABER testing. It becomes clearly evident soon after and it is completed at 2 years of age which is comparable to adult values. The cochlea fully develops at birth as evidenced by wave I latency which is comparable to adult values.     

300例结直肠癌肝转移患者的临床预后分析

目的 探讨结直肠癌肝转移患者的临床特征及预后因素.方法 对300例结直肠癌首发肝转移患者的临床特征及肝转移后的生存情况进行回顾性分析.结果 300例患者中,原发病灶位于结肠者152例,位于直肠者148例.原发肿瘤为管状腺癌272例,黏液腺癌18例,类癌5例,印戒细胞癌4例,鳞癌1例.原发肿瘤为高分化19例,中分化217例,低分化27例.无区域淋巴结转移104例,有区域淋巴结转移162例.原发肿瘤分期为Ⅰ、Ⅱ期62例,Ⅲ、Ⅳ期为237例.同时性肝转移206例,异时性肝转移94例.肝转移灶为单发48例,多发252例.肝转移灶最大直经≤5 cm249例,>5 cm 51例.300例患者转移后中位生存期为19.0个月,肝转移后1、2和5年生存率分别为79.0%、29.0%和3.0%.单因素分析结果显示,患者KPS评分、组织学分级、原发肿瘤T分期、有无区域淋巴结转移、原发肿瘤分期、有无脉管瘤栓、肝转移灶部位、肝转移灶最大直径、肝转移灶数目、同时合并其他转移均与预后有关.多因素分析结果显示,KPS评分、脉管瘤栓、肝转移灶数目、肝转移灶最大直径是结直肠癌肝转移患者预后的独立影响因素.结论 KPS评分、脉管瘤栓、肝转移灶数目和最大直径是结直肠癌肝转移患者预后的影响因素,KPS评分越高、无脉管瘤栓、肝转移灶数目越少、转移灶最大直径越小的患者预后越好.