Search PubMed⌕ Search

Biomedical subjects

L J Peters

Publications and source records attributed to L J Peters.

At least 235 records · Page 13Linked to original sources
PubMed1980

Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells.

The cytotoxic effects in vivo of single doses of either adriamycin (ADM), 1-beta-D-arabinofuranosylcytosine (Ara-C), bleomycin (BLM), cis-diamminedichloroplatinum (II) (cis-DDP), or cyclophosphamide (CY) on murine fibrosarcoma (FSa) cell populations were determined. Tumour cells were separated and synchronized by centrifugal elutriation. Viable tumour cells from selected elutriator fractions were then injected i.v. into whole-body-irradiated mice. Twenty minutes later selected doses of ADM, Ara-C, BLM, cis-DDP or CY were administered to selected groups of these animals. Fourteen days later the mice were killed. Killing of injected tumour cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung colonies per cell injected in treated animals. Under these conditions the response of FSa cells in vivo to the 5 drugs tested differed both qualitatively and quantitatively. Ara-C was S-phase-specific in toxicity. ADM, BLM, and cis-DDP were preferentially toxic to S, G2+M and G1 cells respectively. CY, a drug requiring bioactivation to form alkylating metabolites, was found to be equally toxic to G1 and G2+M enriched populations, but less effective in killing cell populations enriched with early-S cells.

Animals↗
PubMed1980

Inhibition of artificial lung metastases in mice by pre-irradiation of abdomen.

A phenomenon by which pre-irradiation of the abdomen of mice reduced the lung-colony-forming efficiency of i.v.-injected tumour cells is described. The extent of lung-colony inhibition was shown to depend on both the dose and timing of abdominal irradiation. The maximum inhibitory effect was obtained when mice received 1200 rad gamma-irradiation to the abdomen 5--7 days before tumour-cell challenge, but there was no effect when abdominal irradiation was given 1 or greater than or equal to 14 days before challenge, or when radiation doses were less than 600 rad. In mice less than 3 weeks old, the effect was much less marked than in adults. The target tissue which, when irradiated, exerted the inhibitory influence on lung-colony formation was located in the ventral half of the abdomen in all 4 quadrants, and was probably gut. Radioactively labelled tumour cells were arrested normally in the lungs of irradiated mice, but were cleared more rapidly without evidence of sequestration in the irradiated gut. The most plausible mechanism seems to be that irradiation of the gut induces the production of natrual killer cells with anti-tumour activity, though this has not been conclusively established.

Abdomen↗
PubMed1980

Dose response of squamous cell carcinomas of the upper respiratory and digestive tracts.

Dose-response curves have been computed for 5 tumour sites of the head and neck region, using 2 regression models. In agreement with clinical observation, a significant increase has been found from moderate to high control rates with modest dose increases for exophytic tumours (T1 + T2 retromolar trigone-anterior faucial pillar and T2 + T3 supraglottic larynx). Further significant increases in local control after modest dose increases are not obtained when the control rate is already high and the slope of the dose-response curve consequently diminished. Despite unsatisfactory (50%) control rates for large heterogeneous tumours (T3 + T4 pharyngeal walls), further increases cannot be obtained without excessive doses because the curve flattens at the 50% control rate level.

Carcinoma, Squamous Cell↗
PubMed1979

Phase-specific cytotoxicity in vivo of hydroxyurea on murine fibrosarcoma cells synchronized by centrifugal elutriation.

The S-phase-specific cytotoxicity of hydroxyurea (HU) was tested on synchronized murine fibrosarcoma (FSa) cells lodged in the lungs of C3Hf/Bu mice. FSa cells from primary asynchronous cultures were separated and synchronized on the basis of size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations. After elutriation, 8000 viable FSa cells from each fraction, along with 10(6) heavily irradiated tumour cells (unseparated) were injected i.v. into whole-body-irradiated mice (20 per group). Under these conditions, 95% of the injected cells, regardless of size or position in the cell cycle, are arrested in the lungs. Twenty minutes later, hydroxyurea (HU, 1 mg/g) was administered i.p. into 10 animals of each group. Fourteen days later the animals were killed, their lungs removed and fixed, and the number of macroscopic tumour nodules counted. Killing of the initially injected cells by HU, as evidenced by a reduction in lung colonies in treated animals, correlated with the precentage of S-phase cells in each fraction. The greatest effect, an 80% reduction in colony number, was seen in Fraction 8, containing the largest percentage of S-phase cells (65%). These results demonstrate the usefulness of this procedure as a rapid method for characterizing the phase specificity of chemotherapeutic drugs in vivo.

Animals↗
PubMed1979

Oral complications of bone marrow transplantation in adults with acute leukemia.

In recent years bone marrow transplantation has become increasingly feasible for treating adult acute leukemia unresponsive to chemotherapy. However, the technique is not without significant intrinsic morbidity. The mouth is a singularly sensitive reflector of the cytotoxic, infectious, and hemorrhagic complications and of the graft-vs-host reactions associated with bone marrow transplantation in refractory acute leukemia.

Bacterial Infections↗
PubMed1979

Radiobiological considerations in the use of total-body irradiation for bone-marrow transplantation.

On radiobiological grounds, a therapeutic advantage should result when total body irradiation (TBI) in preparation for bone-marrow engraftment is given as a fractionated course, rather than as a single exposure at logistically reasonable dose rates. This is because cells of hemopoietic origin in general show less capacity for repair of sublethal radiation injury than do cells of other organs. Dose-limiting lung tolerance, in the context of fractionated TBI, is estimated to be at least 12 Gy (without correction) in increments of 2 Gy regardless of dose rate. A practical method for delivering TBI using a high-energy linear accelerator is described.

Animals↗
PubMed1979

Preliminary report of the M. D. Anderson Hospital/Texas A & M variable energy cyclotron fast-neutron therapy pilot study.

The records of 248 patients treated with fast neutrons and of 102 comparable but nonrandomized control patients treated conventionally with photons, surgery, or combined surgery and photon irradiation were reviewed. Fast neutron therapy included treatment with neutrons alone, a neutron boost after photon therapy, or a schedule of alternating neutron and photon treatments (mixed beam). The results with mixed beam irradiation were superior to those obtained with the other neutron therapy techniques, and compared favorably with the results of standard treatment methods. However, the lack of a conclusive advantage for neutron therapy in this pilot study illustrates the need for on-going randomized clinical trials.

Adenocarcinoma↗
PubMed1979

Autologous bone marrow transplantation in relapsed adult acute leukemia.

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Adolescent↗
PubMed1979

The critical influence of timing of combined modality cytoreductive regimens.

When sequential high dose drug-radiation cytoreductive regimens are employed, the interval between chemotherapy and total body irradiation (TBI) can markedly influence both toxicity in rapid cell renewal systems and the probability of successfully ablating normal and malignant hemopoietic stem cells. This is primarily due to the intense regenerative responses manifested by cells of these tissues that survive the first cytoreductive insult. Since the total doses of chemotherapy and radiation used are limited by toxicity to slowly or non-proliferating tissues, the best therapeutic effect should be obtained when the interval between chemotherapy and TBI is the shortest consistent with acceptable toxicity to rapid cell renewal systems, provided adequate time for drug metabolism and excretion is allowed to minimize the risk of interactive toxicity. In mice treated with piperazinedione 50 mg/m2 and fractionated TBI, the optimal interval between drug administration and irradiation is 3-4 days.

Animals↗