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T Tenforde

Publications and source records attributed to T Tenforde.

8 recordsLinked to original sources

Molecular and cellular radiobiology of heavy ions.

Quantitative studies at the BEVALAC have demonstrated some of the physical and radiobiological factors that promise to make accelerated heavy ions important for the therapy of cancer. The measured physical dose-biological effect relationships allow the safe and effective delivery of therapeutic schedules of heavy ions. Among the charged particle beams available, carbon, neon and helium ions in the "extended Bragg peak mode" have optimal physical and biological effectiveness for delivery of therapy to deep seated tumors. The depth-dose profiles of these beams protect intervening and adjacent tissues as well as tissues beyond the range of the particles. For the treatment of hypoxic tumors, silicon and argon beams are being considered because they significantly depress the radiobiological oxygen effect in the region of the extended Bragg ionization peak. The depth-effectiveness of the argon beam is somewhat limited, however, because of primary particle fragmentation. Silicon beams have a depth-dose profile which is intermediate between that of neon and argon, and are candidates to become the particle of choice for maximizing high LET particle effects. Heavy accelerated ions depress enzymatic repair mechanisms, decrease variations of radiosensitivity during the cell division cycle, cause greater than expected delays in cell division, and decrease the protective effects of neighboring cells in organized systems. Near the Bragg peak, enhancement of heavy particle effects are observed in split dose schedules. Late and carcinogenic effects are being studied. With the newly developed Repair-Misrepair theory we can quantitatively model most observations.

Animals↗

Treatment of cancer with heavy charged particles.

A clinical radiotherapeutic trial using heavy charged particles in the treatment of human cancers has accrued over 400 patients since 1975, 378 of whom were treated with particles and 28 with low LET photons as control patients. Heavy charged particle radiotherapy offers the potential advantages of improved dose localization and/or enhanced biologic effect, depending on particle selected for treatment. Target sites have included selected head and neck tumors, ocular melanomata, malignant gliomata of the brain, carcinoma of the esophagus, carcinoma of the stomach, carcinoma of the pancreas, selected juxtaspinal tumors and other locally advanced, unresectable tumors. A Phase III prospective clinical trial has been started in carcinoma of the pancreas using helium ions. Phase I-II studies are underway with heavier particles such as carbon, neon and argon ions in order to prepare for prospective Phase III trials. Silicon ions are also under consideration for clinical trial. These studies are supported by the United States Department of Energy and National Institutes of Health.

Adult↗

Effect of combined misonidazole and accelerated neon ions on a human melanoma transplanted into nude mice.

The response to accelerated neon ions of human Nall melanomas growing in nude mice was measured by an in vitro colony-forming assay following in situ tumor irradiation in the midposition of a 10-cm extended-peak ionization region. Values of the relative biological effectiveness (RBE) for peak neon ions compared with 60Co gamma radiation were 3.2 and 3.4, respectively, at the 1% and 10% survival levels. Following irradiation with peak neon ions, the repair of potentially lethal damage (PLD) was comparable to that observed after gamma irradiation. When misonidazole (1 mg/g intraperitoneal dose) was administered in combination with extended-peak neon ions, the drug enhancement ratio (ER) at the 1% survival level was 1.5 if the tumors were removed and plated in vitro immediately following irradiation, and 1.9 if tumor excision and plating were delayed for greater than 6 hours. Administration of misonidazole completely inhibited PLD repair following either gamma irradiation or extended-peak neon-ion irradiation.

Animals↗

Decreased surface charge and accelerated senescence of red blood cells following neuraminidase treatment.

Female LAF1 mice were given single or repeated injections of V. cholerae N'ase and the effects on circulating RBC surface charge and life span were determined. Intravenous injection of N'ase caused a rapid decrease in RBC surface charge of approximately 14 percent, and survival of such treated cells was reduced by approximately one fifth by virtue of an acceleration of senescence. When RBC's were treated in vitro with N'ase, a comparable (14 to 17 percent) reduction in surface charge was seen. Such cells, when injected into intact mice, showed a similar acceleration of senescence. When N'ase was injected intravenously into splenectomized mice, RBC survival was similar to that of controls. Intravenous injection of N'ase 1 hour before injection of labeled RBC's did not alter RBC survival nor did it accelerate the clearance of carbon particles by the RES. These results indicate that N'ase accelerates senescence in treated mouse erythrocytes by acting on the RBC's and not by activating the RES. Absence of this effect in splenectomized mice implicates the spleen as the sensor of the induced alterations in surface charge. These results and those recently reported for treated RBC's in the dog, rat, rabbit, and man suggest that at least a portion of the phenomenon of RBC senescence may be related to the loss of RBC surface charge.

Animals↗