We have retrospectively reviewed the treatment results of postoperative radiotherapy (RT) for advanced oral cavity cancers. The purpose of this study was to determine the impact of anatomic subsite on the results of treatment. Between 1975 and 1985, 51 patients with squamous cell carcinoma of the oral tongue (OT = 29 patients) and floor of mouth (FOM = 22 patients) were treated with combined surgery plus RT. All had an indication(s) for RT including advanced primary disease (T3 or T4) (29 patients), close or positive margins (34 patients), and multiple positive neck nodes and/or extracapsular extension (41 patients). With a median follow-up of 6 years, the 5-year actuarial local control rate was 74% and the rate of distant metastasis (DM) was 34%. Despite the similar T stage, margin status and median RT dose, the 5-year actuarial local failure rate was 38% for OT vs. 11% for FOM (p = 0.03). Furthermore, the median survival after recurrence was 9 months for OT and 40 months for FOM (p = 0.02). At 5 years the determinate survival for both sites was (55%), and the likelihood of developing a second malignancy was 31%. The likelihood of developing DM was 50% for FOM (N0-N1 = 3 of 12, N2-N3 = 8 of 10) and 21% for OT (N0-N1 = 4 of 21, N2-N3 = 1 of 8). This study highlights significant differences between FOM and OT cancers in response to combined surgery and RT. Future strategies should be directed at the enhancement of local control for OT and better systemic therapy for those with advanced N-stage FOM.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗

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The current status of adjuvant hormonal therapy combined with radiation therapy for localised prostate cancer.

Analysis of the results of treatment of localised prostate cancer with radiation and surgery has identified patients who are at high risk of developing metastatic dissemination. High histologic grade, serum prostate specific antigen above 20 ng/ml, extension beyond the capsule of the prostate, and involvement of lymph nodes are highly predictive of metastatic risk. Antiandrogen therapy has high rates of activity in the treatment of overt metastatic disease prompting its assessment as an adjuvant treatment added to radiation therapy. There are now major prospective randomized trials which have been completed. The current evidence indicates that a large survival benefit ensues when antiandrogen therapy is added to radiation for appropriately selected patients. This adjuvant approach is likely to become the standard of care. Strategies for further enhancement of adjuvant therapy are discussed.

Androgen Antagonists↗

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Advances in radiation technology can improve survival and quality of life for cancer patients.

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Brain Neoplasms↗

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Sequence and topology of a model intracellular membrane protein, E1 glycoprotein, from a coronavirus.

In the eukaryotic cell, both secreted and plasma membrane proteins are synthesized at the endoplasmic reticulum, then transported, via the Golgi complex, to the cell surface. Each of the compartments of this transport pathway carries out particular metabolic functions, and therefore presumably contains a distinct complement of membrane proteins. Thus, mechanisms must exist for localizing such proteins to their respective destinations. However, a major obstacle to the study of such mechanisms is that the isolation and detailed analysis of such internal membrane proteins pose formidable technical problems. We have therefore used the E1 glycoprotein from coronavirus MHV-A59 as a viral model for this class of protein. Here we present the primary structure of the protein, determined by analysis of cDNA clones prepared from viral mRNA. In combination with a previous study of its assembly into the endoplasmic reticulum membrane, the sequence reveals several unusual features of the protein which may be related to its intracellular localization.

Amino Acid Sequence↗

PubMedDate not supplied

Delivery of adenoviral vectors to the prostate for gene therapy.

Prostate cancer has become the most frequently occurring cancer and the second leading cause of cancer deaths in men. One novel approach to combat prostate cancer is gene therapy. A replication-deficient recombinant adenoviral vector (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) (lacZ) under the control of the Rous sarcoma virus promoter was used to determine which delivery route was best for the transduction of adenoviral vectors to the prostate. Using a canine model, adenoviral vectors were administered by intravenous, intra-arterial, and intraprostatic (i.p.) injections. After injections, the expression of the lacZ gene was measured in canine prostates as well as in various other organs to determine the distribution of the disseminated adenoviral vector by (a) the percentage of cells expressing lacZ in situ (5-bromo-4-chloro-3-indolyl beta-D-galactoside staining), (b) beta-gal enzymatic activity (colorimetric beta-gal assay), and (c) polymerase chain reaction of genomic DNA using primers specific for the adenoviral genome. An i.p. injection of the adenoviral vector resulted in a greater transduction rate and expression level of lacZ in the prostate than either intravenous or intra-arterial (inferior vesical/prostatic artery) injections. Thus, an i.p. (or intratumoral) injection seems to be the best route to treat local regional prostate cancer by viral-based gene therapy.

Adenoviridae↗

PubMedDate not supplied

Development of an ex vivo model to investigate the effects of altered haemodynamics on human bypass grafts.

The insertion of vein grafts into the arterial circulation may contribute to vessel wall thickening and accelerated atherosclerosis, a common feature of late vein graft failure. We aimed to develop a model suitable for investigation of the effects of altered haemodynamics on human saphenous vein following its implantation into the arterial circulation. Segments of human saphenous vein obtained from patients undergoing coronary artery bypass surgery were sutured at each end to PTFE and placed into a flow system. Pressure and flow rates to stimulate the arterial and venous systems were achieved. A theoretical model of the flow chamber was created and computational fluid dynamics software (FLOTRAN, Swanson Analysis Systems) was used to determine the flow profile within the model. In summary, a flow model has been developed to investigate the effect of altered haemodynamics on the molecular and pathological changes that occur in vein grafts incorporated into the arterial circulation.

Blood Flow Velocity↗