Biomedical subjects

G L Schechter

Publications and source records attributed to G L Schechter.

At least 19 recordsLinked to original sources

PubMed1992

Frequent p53 mutations in head and neck cancer.

Squamous cell carcinomas of the head and neck (SCCHN) are associated strongly with the use of tobacco and alcohol, but little is known about the molecular pathogenesis of these tumors. In the present study, we analyzed SCCHN for mutations in the tumor suppressor gene p53 by immunocytochemistry and complementary DNA sequencing. Overexpression of p53 protein was detected in 13 (100%) of 13 SCCHN cell lines and in tumor cells cultured directly from 10 (77%) of 13 patients with SCCHN. Direct evidence for p53 mutations was obtained by sequencing p53 complementary DNA from eight SCCHN cell lines and two tumor xenografts. The genetic alterations included seven missense mutations resulting in single amino acid substitutions, a mutation encoding a stop codon, one 10-base pair deletion, and one 2-base pair addition. All seven missense mutations were G to T transversions, five of which were clustered at codons 245 and 248. A similar high frequency of G to T transversions predominates in lung cancer, another tobacco-related disease. Mutation of the p53 gene is the most common genetic alteration detected in SCCHN and implicates this gene locus as a critical site of specific damage by mutagenic carcinogens in tobacco, one of the important risk factors in the etiology of this disease.

Adult↗

PubMed1992

Genetic alterations in head and neck cancer.

Mutations of the ras gene family appear to be an uncommon genetic alteration in SCCHN. A common region of DNA amplification on chromosome 11q13 has been identified in SCCHN. A cluster of proto-oncogenes (int-2, hst-1, bcl-1, prad-1) has been localized to the 11q13 region. Studies are needed to determine the critical genes in 11q13 whose expression drive the amplicon. Mutations of the p53 tumor suppressor gene are the most common genetic alteration in SCCHN. The hope is that dysregulated oncogenes or tumor suppressor genes may be targets for specific therapy.

Carcinoma, Squamous Cell↗

PubMed1991

A basic model to study acoustic evaluation of airway obstruction.

Listening to a human airway to determine obstruction is a highly subjective art and an important clinical tool. Sophisticated acoustic monitoring techniques should be developed and tested in the laboratory before they are applied in the clinic. We describe construction of an acoustic tube model to study the mechanism of noise generation in a simulated obstructed human airway. Spectral differences were demonstrated between different amounts and locations of obstruction and changes resulting from variations in airflow using Fast-Fourier transform techniques. With this analog model, systematic research can be conducted to define expected patterns in obstructed human airways for use in the clinical setting.

Air Pressure↗

PubMed1991

Growth and histopathology of human head and neck squamous cell carcinoma implanted intraorally in nude mice.

A human squamous cell carcinoma (SCC) from the floor of the mouth (FOM) was implanted by a needle aspiration technique in the FOM site of athymic nude mice. Mice were killed at 3-week intervals, and the oral cavity, mandible, and neck were sectioned and examined histologically. Tumor growth was observed in 65% of the animals, with histologic features consistent with the engrafted human invasive SCC. These features included invasion of connective tissue in 92%, invasion of muscle in 77%, invasion and destruction of bone in 54%, and vascular invasion in 15% of the mice. In contrast, FOM tumor implanted subcutaneously on back sites of nude mice was totally encapsulated by fibrous connective tissue with evidence of capsular invasion. SCC from other head and neck sites showed similar locally invasive growth after intraoral implantation in nude mice. The results demonstrate the invasive characteristics of human head and neck SCC grown in the homologous oral cavity site in nude mice and support the nude mouse as a biologically relevant in vivo model in the investigation of the biologic characteristics and therapy of head and neck carcinoma.

Animals↗

PubMed1990

Amplification of the int-2 gene in human head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (SCC) from 21 patients were analyzed for structurally rearranged or amplified proto-oncogenes by Southern blot hybridization. The int-2 proto-oncogene was amplified 3-5 fold in 5 (50%) of 10 laryngeal SCC and 2-3 fold in 5 (45%) of 11 nonlaryngeal SCC of the head and neck. Adjacent histologically normal tissue from the same patients had single int-2 gene copy number. Coamplification of int-2 and the epidermal growth factor receptor (c-erbB-1) gene was found in one laryngeal SCC and one SCC metastatic to the neck. No amplification or structural alterations of proto-oncogenes c-erbB-2/HER2, c-myc, H-ras-1, or K-ras-2 was detected in any of the head and neck tumors. In a survey of head and neck tumor-derived cell lines, int-2 was amplified 9 fold in a hypopharyngeal tumor cell line (FaDu), but not amplified in 3 laryngeal tumor cell lines. int-2 has been localized to the q13 band of chromosome 11. We used chromosome 11 specific probes to demonstrate that int-2 amplification was not due to complete or partial chromosome 11 duplication. int-2 amplification was localized to 11q13, but did not extend to the ets-1 locus 11q23. The results indicate that int-2 is frequently amplified in SCC of the head and neck and suggest that int-2 amplification may correlate with clinical disease progression.

Carcinoma, Squamous Cell↗

PubMed1988

Growth of head and neck squamous cell carcinoma in nude mice: potentiation of laryngeal carcinoma by 17 beta-estradiol.

We successfully transplanted and serially perpetuated human head and neck tumors in nude mice by using tumor tissue derived from 10 of 14 (71%) independently obtained surgical specimens. Tumor growth was achieved with specimens derived from cancers of the floor of the mouth, hypopharynx, and larynx. Tumors in nude mice retained their histological stage of differentiation and human species origin. Prompted by reports of increased estrogen receptors in laryngeal carcinomas, we tested the effect of estradiol treatment on the growth of laryngeal tumor implants. Time to tumor formation was decreased and tumor size was increased in estradiol-treated animals relative to placebo-treated animals. The results demonstrate that estradiol treatment potentiates growth of laryngeal tumors in nude mice. This tumor model can also be used to evaluate antihormonal therapy in the treatment of some laryngeal carcinomas.

Animals↗

PubMed1988

Cancer of the hypopharynx and cervical esophagus: management concepts.

Treatment of cancer of the pharyngoesophageal region requires a multidisciplinary team approach using combined radiotherapy and surgery. Since patients with this cancer usually present for treatment after their tumors have reached advanced stages, their nutritional status is usually poor and must be dealt with prior to instituting therapy. Resection must be radical and usually produces a multifunctional defect. Reconstructive choices are varied, depending on the patient's general condition, the abilities of the head and neck surgeon, and the availability of other surgical specialties to help with reconstruction. Although treatment has become safer and provides a more functional existence, pharyngoesophageal cancer is still a deadly disease that kills two out of three patients.

Combined Modality Therapy↗

PubMed1987

Functional evaluation of pharyngoesophageal reconstructive techniques.

This work represents a 12-year experience from the Eastern Virginia Medical School, Norfolk, with 115 patients who had pharyngoesophageal resections for cancer treatment. Each patient received reconstruction by one of four major techniques: deltopectoral flaps (n = 43), pectoralis myocutaneous flaps (n = 36), gastric pull-ups (n = 19), and free jejunal autografts (n = 17). An analysis of the procedures with emphasis on the functional results indicates that each technique has advantages in specific circumstances. Guidelines for the application of these techniques are presented.

Adolescent↗

PubMed1987

Free jejunal transfer for the reconstruction of pharyngeal and cervical esophageal defects.

Free jejunal transfer is a useful alternative for the reconstruction of defects of the pharynx and cervical esophagus. We describe 17 patients who received free jejunal grafts between 1980 and 1984 at the Eastern Virginia Medical School. The rationale and indications for the procedure are discussed. We emphasize certain technical considerations and improvements.

Adult↗

PubMed1987

Ectopic gastric mucosa in the cervical esophagus.

Ectopic gastric mucosa is a known entity of the mid and lower esophagus which was initially described by Schmidt in 1805. The presence of ectopic gastric mucosa in the cervical esophagus, however, was not described. A review of the literature reveals that ectopic gastric mucosa of the cervical esophagus is not uncommon, but symptoms rarely have been attributed to its presence. This paper reports five patients with isolated inflamed ectopic gastric mucosa in the cervical esophagus who presented with odynophagia and/or dysphagia. Physical examination was unremarkable in each case, and an acid barium esophagram was negative in four of five patients. Factors that distinguish these patients from other cases of odynophagia and dysphagia, as well as detailed clinical findings and treatment, are described. Debate exists as to whether the origin of ectopic gastric mucosa is congenital or acquired. The embryology, gross and microscopic anatomy, and pathologic features are outlined. Patients with persistent dysphagia should have flexible fiberoptic esophagoscopy with an index of suspicion to the existence of ectopic gastric mucosa. Inflamed or ulcerated ectopic gastric mucosa in the cervical esophagus should be treated to relieve symptoms and because of the potential for complications.

Adult↗

PubMed1986

Management of panesophageal cancer by blunt resection without thoracotomy and reconstruction with stomach.

Encouraged by their experience since 1978 with blunt esophagectomy and gastric reconstruction in the management of pharyngolaryngeal malignancy, the authors have extended their use of this technique to the management of thoracic esophageal cancer. A study of 43 blunt esophageal resections is presented; 23 were performed in the management of pharyngolaryngeal cancer, and 20 were performed (22 attempted) for the resection of intrathoracic esophageal cancer. In the first group, two deaths occurred secondary to liver failure in cirrhotic patients with moist ascites. One death occurred due to anastomotic leak in the neck of a patient with laryngeal cancer treated with extended mediastinal dissection and tracheal resection for surgical and radiation failure. Two tracheal injuries occurred; one could be managed through the neck, and one required thoractomy for repair. In the 20 resections performed for intrathoracic cancer, there were no deaths, no tracheal injuries, and one chest was explored for bleeding in the splenic bed, which decompressed itself into the right chest. The overall mortality was 7.5%. The evaluation emphasizes: The applicability of this technique for the management of esophageal problems at all levels. The safety of the technique, particularly in the typical population with advanced aged and severe underlying medical illness. Good functional results with palliation and/or cure. The benefit of intact mediastinal pleura in avoiding certain thoracic complications. The authors conclude that blunt esophagectomy is a safe resection procedure with limited morbidity and mortality, and that gastric reconstruction is reliable and affords excellent functional results. They are encouraged to continue management of panesophageal cancer with this technique.

Actuarial Analysis↗

PubMed1985

Macroglossia: etiologic considerations and management techniques.

Tongue enlargement of varying degrees occurs in many people and often requires no therapy. However, marked tongue enlargement, when present, requires direct intervention. In this case, the otolaryngologist is presented with a dilemma, for the etiology of the problem is often obscure. In many cases, the tongue enlargement is secondary to systemic disease, and medical management is indicated. When tongue reduction is indicated, there are many modalities available. Of these, only excision offers an acceptable functional result with minimal morbidity. Even large protuberant tongues can be reduced with minimum difficulty. The type of tongue excision can be tailored to the involved area and to special patient requirements. The problem of macroglossia is explored and management techniques are reviewed to present an alternative for optimal management of the enlarged tongue.

Acromegaly↗

PubMed1973