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L J Peters

Publications and source records attributed to L J Peters.

At least 253 records · Page 14Linked to original sources
PubMed1978

Enhancement of lung colony-forming efficiency by local thoracic irradiation: interpretation of labeled cell studies.

The dynamics of 125IUdR-labeled tumor cell retention in the lungs have been compared with the efficiency of lung colony formation over a wide range of inoculum sizes in normal mice and in mice pretreated with 1000 rads local thoracic irradiation (LTI). These studies indicate that the increase in lung colony yield after LTI cannot be ascribed to improved intravascular trapping or interstitial lodgement of tumor cells. Hypotheses purporting that active specific or nonspecific host defense might be impaired by LTI were reassessed but rejected in favor of the idea that radiation-induced alterations in the physiological mocroenvironment of the lungs improve an intrinsically poor survival capability of intravenously disseminated tumor cells.

Animals↗
PubMed1977

The influence of stress and stress hormones on the transplantability of a non-immunogenic syngeneic murine tumor.

Quantitative transplantation assays of a syngeneic murine adenocarcinoma have been used to investigate the effects of stress hormones and tumor take probability. Cortisol, injected intraperitoneally one hour before and 3 hours after tumor cells, caused a dose dependent reduction of TD50 (number of tumor cells required for 50% takes) by factors of from 4 at a total dose 4 microng/g to 68 at 400 microng/g. ACTH, given at 0.2 I.U. daily for 9 days spanning the time of tumor cell injection, reduced the TD50 2.5-fold, indicating that the peak gluco-corticoid level achieved, rather than its duration, was of greater significance. Adrenaline, while much less effective than cortisol, produced an 8-fold reduction in TD50 at its maximum tolerable dose. The effect of cortisol simulated that of whole body irradiation (WBI), and while both these agents depress immune reactivity, evidence is presented to suggest that immunological mechanisms are not responsible for their effect. WBI constitutes a systemic stress, and the demonstration that surgical trauma (laparotomy) could also reduce the TD50 for this tumor suggested that both might act via endogenous glucocorticoids. However, the failure of prior total adrenalectomy of mice to abrogate the effect of either WBI or laparotomy indicated that stress hormones were not essential intermediaries. It is concluded that both stress hormones, especially glucocorticoids, and stressful procedures acting independently of stress hormones, can facilitate tumor transplantation.

Adrenal Glands↗
PubMed1977

Pitfalls in the use of the lung colony assay to assess T-cell function in irradiated mice.

Mice depleted of T lymphocytes by thymectomy, whole-body irradiation and bone-marrow reconstitution showed a marked increase in susceptibility to the development of lung colonies after i.v. injection of cells of an immunogenic fibrosarcoma. However, a similar increase was observed in unthymectomized, irradiated and reconstituted mice that had recovered their T-cell function, as evidenced by rejection of allogeneic skin grafts. In both thymectomized and unthymectomized mice subjected to whole-body irradiation, the lung-colony-forming efficiency was high 1 day after irradiation, declined to a minimum at 7 days, and thereafter increased again, unless the animals were held in a pathogen-free environment. Reconstitution of T-cell-depleted mice with thymocytes and/or a thymic lobe graft tended to increase further, rather than reduce, lung-colony-forming efficiency. Induction of profound lymphopenia, by irradiation of the whole body except the thorax, did not significantly increase lung colony yields. These studies show that the lung colony assay is not a reliable method of assessing T-cell function in irradiated mice.

Animals↗
PubMed1976

Modification of the radiocurability of a syngeneic murine squamous carcinoma by its site of growth, by electron-affinic drugs, and by ICRF 159.

A series of TCD50 experiments using a spontaneously arising, syngeneically transplated, murine squamous carcinoma is reported. Tumours implanted intradermally and irradiated while they remained superficial had a small but nonetheless cure-limiting hypoxic fraction of cells (TCD50 3,324-4,257 rad). The hypoxic fraction increased dramatically when these tumours invaded the subcutaneous tissues, or when tumours were implanted subcutaneously (TCD50 greater than 5,544 rad). Pre-treatment of mice with the electron-affinic drug Ro-07-0582 at a dose of 1 mg/g i.p. 20-30 minutes before irradiation effectively eliminated the hypoxic element from superficaial tumours (TCD50 1.862 rad). The same drug at a dose of 0-25 mg/g reduced the TCD50 for superficial tumours by a factor of 1-87 (3,986-2,134 rad), while another electron affinic drug, metronidazole, given at a dose of 0-25 mg/g reduced the TCD50 by a factor of 1-28 (4,257-3,337 rad). Treatment of mice with the drug ICRF 159, 30 mug/g daily from the time of tumour cell injection until the day of irradiation, reduced the TCD50 in unclamped tumours by less than 1-19. However, a commensurate reduction of TCD50 in clamped tumours suggested that improved tumour vascularization could not explain fully the drug's "radiosensitizing" action. The unique single radiation dose curability of most human skin cancers is discussed in the light of the experimental results, and the possible clinical implication of an increase in hypoxic fraction with tumour invasion is raised.

Animals↗
PubMed1975

A study of the influence of various diagnostic and therapeutic procedures applied to a murine squamous carcinoma on its metastatic behaviour.

An experimental tumour system for the study of metastasis has been developed using a syngeneically transplanted murine squamous carcinoma of spontaneous origin. Implants of the tumour, which does not elicit a significant immune response, grew and metastasized regularly to regional lymph nodes and lungs, in a manner comparable with that of the more malignant types of human epithelioma. The system has been used to test the influece of pre-operative irradiation, regional lymph node excision, tumour biopsy and manipulation, on metastasis. Of these, only pre-operative irradiation with 2000 rad 24 h before tumour excision produced a significant differential effect--a lower incidence of metastasis. By contrast, local radiation therapy sufficient to cause complete tumour regression but insufficient to achieve long-term local cure was shown to result in accelerated metastasis. A highly significant inhibition of metastasis was observed with the drug ICRF 159, but histological features suggested that its anti-metastatic effect in this system did not depend on morphological changes which might prevent dissemination of tumour cells.

Animals↗
PubMed1975

The natural history of metastasis of syngeneic murine squamous carcinoma and the prognostic implications of primary tumour size and duration of growth.

A study has been made of the natural history of metastasis of a spontaneous murine squamous carcinoma implanted into syngeneic recipients--a situation where biologically different tumours and variable "host resistance" are not complicating issues. The time distrubution of deaths from metastatic disease was incompatible with a log-normal distribution but was accurately described by an exponential pattern of survival following an initial lag. While the average life of doomed mice correlated with predictions based on growth rates, there was a wide range of survival times indicating random influences on the evolution of metastitic disease. Insofar as tumours which grew to 20 mm3 or less in 5 days after tumour cell injection failed to initiate metastases, while tumours which reached a size of 120 mm3 or greater (irrespective of duration) produced metastases in 38/39 mice, tumour size was a prognostic index. However, within the size range 33-150 mm3 the correlation between metastatic risk and size was not statistically significant. No correlation between metastatic risk and duration of tumour growth from 6 to 29 days was observed. Two integral functions of tumour size and duration were tested but neither gave a better correlation with metastatic risk than did size alone.

Animals↗
PubMed1975

Enhancement of syngeneic murine tumour transplantability by whole body irradiation--a non-immunological phenomenon.

Experiments were undertaken to test the general validity of the assumption that potentiation of tumour transplantability by sublethal whole body irradiation (WBI) implies some degree of immunological resistance in the intact host. A transplantable carcinoma of spontaneous origin in CBA mice which exhibits a large WBI effect was assayed quantitatively in mice which had been immunologically crippled in terms of allograft acceptance by depletion of thymus derived lymphocytes. The mean number of tumour cells required for 50% successful takes (TD50) in these mice was found to be not significantly different from that in normal controls but highly significantly greater than in WBI mice. On the other hand, in mice which underwent laparotomy immediately before assay, the TD50 was reduced significantly though not to the same extent as in WBI mice. It was concluded that WBI effect was not due to impaired host immunity but possibly to physiological changes resulting from acute stress. The hypothesis that hyperfibrinogenaemia which occurs after both WBI and laparotomy might increase tumour transplantability was rejected because of the lack of correlation between TD50 and fibrinogen levels at different times after each procedure. From this and other work it is apparent that TD50 data, in themselves, give no reliable indication of host immunity.

Adenocarcinoma↗
PubMed1974

The influence of fibrin formation on the transplantability of murine tumour cells: implications for the mechanism of the Révész effect.

Experiments were undertaken to test a new hypothesis for the mechanism underlying the Révész effect. The hypothesis proposes that lethally irradiated (LI) tumour cells enhance the take probability of a small number of transplanted viable (V) tumour cells mixed with them by exerting a thromboplastic effect at the site of injection; local fibrin formation prevents emigration of V cells from the site or secures their survival there. The evidence presented to support this hypothesis is as follows: in the case of 3 isogeneically transplanted tumours, admixed particulate brain extract simulated the effect of LI cells in increasing the take probability of V cells; brain extract simulated the effect of LI cells in greatly delaying the disappearance of (125)IUdR-labelled viable carcinoma cells from the injection site; V cells acquired a raised take probability by their incorporation in fibrin clots; it was confirmed that admixed erythrocytes increased the take probability of V cells; using a newly devised microscopical test for detection of the thromboplastic activity of individual cells, it was found that cell death was almost always required for the display of such activity; lymphocytes and bone marrow cells, ineffective in enhancing the take of V cells, were almost totally devoid of thromboplastic activity. Possible explanations are given for failure of a fibrinogen depleting agent, ancrod (Arvin) to inhibit the Révész effect when administered to recipients. It is concluded that the evidence strongly supports the hypothesis presented whilst seriously weakening the long-standing theories that admixed LI cells act by provision of nutrients or by local quenching of postulated immune reactivity.

Animals↗
PubMedDate not supplied

Early squamous cell carcinoma of the hypopharynx: outcomes of treatment with radiation alone to the primary disease.

BACKGROUND: This retrospective study analyzes the outcome of treatment of a cohort of patients with hypopharyngeal tumors staged T1 or T2 treated with curative radiation alone to the primary tumor. The potential influence of advances in technology and radiobiology are studied. METHODS: Eighty-two patients with early-stage (T1, 19 patients; T2, 63 patients) hypopharyngeal squamous cell carcinomas treated between 1976 and 1992 at the University of Texas M.D. Anderson Cancer Center completed a course of definitive radiotherapy to their primary tumors. Forty-three patients (52%) were node positive, of which 23 (28%) had surgery to their involved necks in addition to radiation. Thirty-six patients (44%) had computerized tomography (CT) as part of the staging workup. Doses to the primary ranged from 60 to 79 Gy. Forty-four patients (54%) in this study were treated with twice-daily radiation (BID). Boosts to gross disease using off spinal cord fields were treated with Co60 gamma rays in 40 patients (49%); 34 (41%) with 6-25 MV x-rays (X), and 8(10%) with an ipsilateral electron beam field. RESULTS: The 2-year actuarial local control rates for patients with T1 and T2 disease were 89% and 77%, respectively. Subgroup analysis of T2 patients showed the following differences in actuarial local control rates at 2 years: BID, 86%; no BID, 60% (p, .004%); CT, 83%; no CT, 71% (p, .1); X boost, 88%; no X boost, 67% (p, .04). The actuarial 2- and 5-year survival rates for all patients were 72% and 52%, respectively. CONCLUSIONS: A majority of patients with early hypopharyngeal lesions are radiocurable. Patients treated with hyperfractionated radiotherapy and off spinal cord fields with 6 MV (or higher energy) x-ray beams had improved local control rates. CT scans assisted in appropriate patient selection for definitive treatment with radiation.

Actuarial Analysis↗
PubMedDate not supplied

Neck surgery in patients with primary oropharyngeal cancer treated by radiotherapy.

BACKGROUND: The role of neck surgery in node-positive patients whose primary tumors are treated by definitive radiotherapy is controversial. This analysis was undertaken to assess the risk of withholding planned neck dissection in patients who obtain a complete nodal response to irradiation. METHODS: We reviewed the records of 100 patients who presented between 1984 and 1993 with oropharyngeal cancers metastatic to the neck and whose primary tumors were treated by radiotherapy using the concomitant boost regimen. Seventy-five patients had their nodal disease treated definitively by radiotherapy; those who had complete clinical resolution of all nodal disease (62) had no planned surgery, while 13 underwent neck dissection for presumed residual disease. The remaining 25 patients had either node excision (8) or neck dissection (17) prior to radiotherapy. RESULTS: There were 8 cases of isolated neck failure of which 3 occurred in the 62 patients who had no planned neck surgery, 0 in the 13 patients who had surgery for presumed residual (pathologically negative in 7). and 5 in the 25 patients who had initial neck surgery. In those who obtained a complete response to definitive radiotherapy, the risk of neck relapse was unrelated to pretreatment nodal size. CONCLUSIONS: The policy of observation of the neck after complete nodal response to full-dose irradiation is both safe and cost effective. Imaging to confirm the resolution of nodal disease is recommended.

Adult↗