Tight-binding inhibitory sequences against pp60(c-src) identified using a random 15-amino-acid peptide library.

A bacteriophage peptide library containing a random 15-amino-acid insert was screened for identification of peptide sequence(s) that bind pp60(c-src). Sequencing the random insert from more than 100 virions indicated that more than 60% of the phage virions that bound to this enzyme contained a GXXG sequence motif in which X was frequently a hydrophobic residue. The GXXG sequence was often repeated as GXXGXXG.

Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid.

Malignant gliomas account for more than 60% of all primary brain tumors in adults. Adjuvant chemotherapy in addition to radical surgery and radiation therapy has provided only a modest increase in survival. Retinoic acid has been shown to have growth-inhibitory activity against glioma cells in culture.

Adenoid cystic carcinoma of the trachea. A report of 2 cases.

Two cases of adenoid cystic carcinomas arising from the trachea are presented. Epidemiology, presenting features, available therapeutic options and a review of the literature are discussed.

Combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas.

Objective: To determine the efficacy of the combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas after failure of either previous radiotherapy alone or previous radiotherapy plus nitrosourea-based chemotherapy.

Methods: Seventy-seven patients with recurrent malignant gliomas were studied. 6-Thioguanine was administered for 4 days before lomustine, and procarbazine was administered for 1 day before and 2 days after lomustine to potentiate lomustine's antitumor effect.

Hypermethylation of the CpG island of p16/CDKN2 correlates with gene inactivation in gliomas.

There is considerable evidence that lack of p16 protein expression is a frequent event in human gliomas. Nevertheless, the molecular mechanisms underlying this absence of p16 protein expression are not completely understood. In some gliomas, homozygous deletions are the main cause of p16/CDKN2 gene inactivation.

Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy.

Purpose: To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy.

Patients And Methods: Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA).

Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment.

This study examined the relationship between cognitive function, tumor malignancy, adjunctive therapy, and lesion lateralization following surgery for intracerebral glioma. Neuropsychological test battery results showed no difference between patients with highly malignant gliomas and those with less malignant gliomas, but differences were found for tumor lateralization and type of therapy. Scores on a test of graphomotor speed were lowest for patients who had received radiation or a combination of radiation and chemotherapy, regardless of lesion location.

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

Background: Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes.

Methods: In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes.

Controversies in the treatment of low-grade astrocytomas and oligodendrogliomas.

Patients with low-grade infiltrative astrocytomas and oligodendrogliomas are young, with a relatively long expected survival because their tumors grow slowly. Unfortunately, because radiation therapy, a potential mainstay of the various treatment options, can cause significant damage to the brain, much controversy revolves around the appropriate management of patients diagnosed with these tumors. In this editorial review, I try to cover reasons for this controversy and conclusions that can be drawn from published studies.

Mutagen sensitivity and risk of gliomas: a case-control analysis.

Although the risk factors contributing to the etiology of brain tumors remain largely unknown, this pilot study suggests that genetically determined sensitivity to environmental carcinogens may play a role in the pathogenesis of these tumors. In this study, we examined short-term lymphocyte cultures from 45 adult malignant glioma patients and 117 age-, sex-, and ethnicity-matched healthy controls for mutagen-induced chromatid breaks and evaluated their family history of cancer, smoking, and demographic variables to ascertain the association between mutagen sensitivity and risk of brain tumors. The mutagen selected was gamma-radiation.

Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis.

Wild-type p53 is involved in several aspects of cell cycle control and suppression of transformation, inducing either apoptosis or G1 block in cell cycle progression. Using a recombinant adenovirus containing the wild-type p53 cDNA, the biological effects of the newly expressed wild-type p53 protein were examined in six human glioma cell lines. Three cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous mutant p53, and the other three (U-87 MG, EFC-2, and D54 MG) expressed wild-type p53.

Mutations of the p16 gene in gliomas.

In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp).

Adenovirus-mediated p16/CDKN2 gene transfer induces growth arrest and modifies the transformed phenotype of glioma cells.

The p16 (MTS1/CDKN2) gene localized at the 9p21 chromosomal region encodes for a cell cycle inhibitor protein and is altered in many human cancers. The frequency of p16 alterations in gliomas exceeds 50%. To restore the missing wild-type p16 gene efficiently in glioma cells an adenovirus vector carrying the full length coding sequence of the wild-type p16 cDNA, Ad5RSV-p16, was constructed.

Toxicity in patients with testicular seminoma treated with radiotherapy. Different dose levels and treatment fields.

The aim of this study was to evaluate the acute and late effects of irradiation in 56 patients with stage I and II testicular seminomas. A retrospective study of patients' records was performed paying attention to the acute and late toxicity of radiation in relation to treatment fields and radiation doses. Treatment groups were compared using the chi squared-test.

Correlation of p53 immunoreactivity and sequencing in patients with glioma.

This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 cDNA from these samples was analyzed by direct sequencing.

Prognostic significance of p53 immunoreactivity in patients with glioma.

Abnormal p53 as revealed by immunostaining has been shown to be a predictor of poor outcome in a variety of malignant tumors. This study examines the relationship of p53 immunostaining and survival in 182 adult patients with gliomas. Tumor tissues obtained from patients with glioma within 4 months of initial diagnosis were investigated by immunohistochemical analysis for detection of p53 protein abnormalities using the monoclonal antibody PAb 1801.

Increased levels of p21WAF1/Cip1 in human brain tumors.

The cdk inhibitor p21WAF1/Cip1 (p21), which can be transcriptionally activated by p53, functions to block cell cycle progression. In this study, we analysed the expression of p21 in normal and reactive brain and in gliomas of various malignancy grades. Southern blotting showed no p21 gene deletion.

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme.

Purpose: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors.

Methods And Materials: Between 1988 and 1992, 83 patients received 1.9-2.

Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53.

The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and inhibits the kinase activity that is required for cell cycle progression. We investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines and found that WAF1/Cip1 expression was detectable in many of the cell lines, even when mutant p53 was present.

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients.

Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.

Purpose: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors.

Methods And Materials: Between 1983 and 1987, study patients received 1.7-1.

The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy.

Purpose: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors.

Methods: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day).