Comparison of the positional cloning methods used to isolate the BRCA1 gene

A critical step in positional cloning is the identificationof candidate genes from a large, genetically defined region.Candidate gene isolation by hybrid selection, genomic sequencing,and direct cDNA library screening identified 45 candidate genefragments (CGFs) from a 600 kb genomic region that containsthe BRCA1 gene. These CGFs define a minimum of 15 genes, sixof which are newly localized to the BRCA1 region. We presentan analysis of the efficiency and the sequences generated foreach of these methods. We also compare our CGF set to thosereported for the BRCA1 region by three other groups, revealinga surprising lack of overlap among the sets.     

Fast neutron irradiation of metastatic cervical adenopathy: the results of a randomized RTOG study

Between 1977 and 1982, 199 evaluable patients with measurable cervical adenopathy were entered on a prospective, randomized RTOG study evaluating the use of fast neutrons in treatment of advanced, inoperable squamous cell carcinomas of the head and neck region. One hundred-eleven patients were randomized to receive mixed beam radiation therapy, and 88 were randomized to the photon control treatment. The complete response rates were 86% for mixed beam vs 75% for photons for Stage N1 nodes, 62% for mixed beam vs 48% for photons for Stage N2 nodes, and 63% for mixed beam vs 53% for photons for N3 nodes. The percents of patients remaining free of their adenopathy for two years were 78% for mixed beam vs 55% for photons for Stage N1 nodes, 39% for both mixed beam and photons for N2 nodes and 24% for mixed beam vs 13% for photons for N3 nodes. The median disease-free status was 20.3 months for mixed beam treated patients and 6.4 months for photon-treated patients. Patients who had clearance of cervical adenopathy survived significantly longer than those who did not.     

Fast neutron therapy for locally advanced head and neck tumors

Between October 1972 and April 1979, 187 patients with locally advanced head and neck tumors were treated with 50 MeV_d→Be neutrons or with conventional treatment in the M. D. Anderson Hospital-Texas A & M University variable energy cyclotron (MDAH-TAMVEC) program. Of these, 114 patients were treated in pilot studies and 73 in a randomized clinical trial. In the pilot studies, 49 patients were treated with neutrons alone, 25 with mixed-beam irradiation (two neutron and three photon fractions per week), and 40 with conventional treatment (surgery, photons, or combined surgery and photons). There was no appreciable difference among patients in these studies with regard to local tenor control or servival. However, the patients in the conventional-treatment pilot study had less advanced disease than those in either of the other studies. The complication rates in the neutrons-only and conventional-treatment studies were significantly greater than the complication rate observed in the mixed-beam pilot study. In the randomized clinical trial, 41 patients were treated with mixed-beam irradiation and 32 with photon irradiation. The preliminary results of this trial show a slight superiority with mixed-beam irradiation. In the mixed-beam group, 61% had local tumor control, 7% developed major complications, and 4996 were alive at the time of analysis; whereas in the photon group, 47% had local tumor control, 3% developed major complications, and 25% were alive at the time of analysis.     

Competitive enzyme-linked immunoassay for Factor VIII antigen.

We describe a competitive enzyme-linked immunoassay for Factor VIII antigen. Binding of anti-factor VIII to solid-phase Factor VIII antigen is competitively inhibited by the free factor VIII antigen that is to be measured. The amount of anti-Factor VIII bound to solid-phase VIII is measured by applying in sequence a heterologous bridging antibody and a soluble antibody/enzyme immune complex. The soluble complex used was rabbit antiperoxidase/horseradish peroxidase. Peroxidase activity is inversely proportional to the Factor VIII antigen concentration in the original test plasma and is measured spectrophotometrically. The assay can be performed in as little as 4 h with only a microtiter plate, antisera, antigen, and a spectrophotometer. It is sensitive to 0.05 units of Factor VIII antigen per milliliter, and reproducibility, linearity, and normal range are similar to those reported for other techniques.     

MiRNAs and Their Association with Locoregional Staging and Survival Following Surgery for Esophageal Carcinoma

Background

Prognostic and staging information for esophageal cancer impacts clinical decision making. miRNAs, a newly discovered class of biomarkers and their expression might add additional information relevant to this. In this study we evaluated the expression of selected miRNAs and their relationship to tumor stage and survival in patients with locally advanced tumors following esophagectomy.

Materials and Methods

A total of 43 individuals undergoing esophagectomy (without neoadjuvant therapy) for locally advanced but not metastatic (pT2/3; pN0/1) disease (22 adenocarcinoma [EAC], 21 squamous cell carcinoma [SCC]) were included in this study. Perioperative clinical and survival data were collected and managed on a database. The expression of miR-21, miR-106a, miR-148a, miR-205 in formalin-fixed paraffin-embedded specimens was evaluated by TaqMan qPCR assays. Expression was compared with clinicopathological features of the cancers and outcome.

Results

In EAC, miR-148a expression levels were inversely associated with cancer differentiation. miR-21 expression levels were higher in SCC if distant lymph node metastases were present. miR-148a levels were lower when EAC was more proximally located, and miR-21 levels were lower when SCC was more proximal. miR-106a and miR-148a were lower in patients with SCC who developed recurrent disease or had a tumor-related death.

Conclusions

In patients with locally advanced esophageal squamous cell carcinoma, but not adenocarcinoma, alterations in the expression of miR-21 correlate with tumor location and lymph node status. Furthermore, miR-106a and miR-148a expression correlates with disease recurrence and tumor-related mortality. miRNA markers might inform the initial assessment of these patients, and predict those at higher risk of postsurgical recurrence.