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Biomedical subjects

J V Moore

Publications and source records attributed to J V Moore.

108 records · Page 6Linked to original sources
PubMed1982

Gross and cellular response of intestinal crypts to single and fractionated doses of vincristine plus radiation: the influence of time between modalities.

The response of intestinal crypts to single doses and four equal, daily fractions of vincristine (VCR) plus gamma-rays, has been measured by the crypt microcolony assay. Measurements were made for VCR given either 7 hours or 1 min before radiation. For the 7-hour interval, fractionating the VCR dose markedly increased the efficacy of the combination treatment. However at 1-min interval, no injury additional to that for gamma-rays alone could be demonstrated, with either one or four fractions. Histopathological studies showed that both VCR and gamma-rays alone caused cell death, but with different distributions in the crypt. For combined treatments, both VCR-and gamma-type damage could be recognized with the 7-hour interval, but at 1 min only gamma damage. It is suggested that mitotic delay induced by radiation may permit the repair of injury caused by simultaneously-delivered VCR.

Animals↗
PubMed1980

Survival of intestinal crypts after treatment by adriamycin alone or with radiation.

A survival curve has been established for jejunal crypts of BDF1 mice treated by single i.p. doses of the antibiotic agent adriamycin. The threshold dose and Do were twice that for marrow CFU-S of these mice. The overall extrapolation number of the crypt survival curve was very low (1.3 +/- 0.13) compared to the value for gamma radiation. This observation is discussed with respect to the interpretation of crypt survival curves. We were unable to demonstrate any enhancement by adriamycin (reduction in Dq) of the response of microcolony-forming cells to radiation given immediately before the drug.

Animals↗
PubMed1980

Dynamic histology of a rat hepatoma and the response to 5-fluorouracil.

The cellular response of the rat hepatoma 3924A to a single intraperitoneal injection of 5-fluorouracil has been measured in respect of the spatial relationship of the cells to the tumour microvasculature. In this tumour the parenchyma is arranged in cords approximately 150 micron thick around central capillaries. For untreated tumours, those cells at distance less than 80 micron from the capillary had a mean [3HTdR labelling index of 39% and a mitotic index of 2.1%, while for those cells more than 80 micron away the values were 14% and 0.8% respectively. Two days after 150 mg/kg of 5-fluorouracil, mean cord thickness was reduced by 25% and did not recover to the control level until 11 days after treatment. This was also true for the mitotic index. Recovery of the labelling index was complete 2 days earlier. Although absolute values of parameters were different in the populations adjacent to and remote from the capillary, the time course of recovery was similar, with a 'growth spur' 7 to 9 days after treatment. The results from this histologically-based assay have been compared with those from biochemical/biophysical assays that sample the overall tumour population.

Animals↗
PubMed1979

Ablation of murine jejunal crypts by alkylating agents.

The gut microcolony assay has been used to measure damage to intestinal crypts by single and split doses of 3 alkylating agents: mechlorethamine hydrochloride (HN2), bis-chloroethyl-nitrosourea (BCNU) and isopropyl methane sulphonate (IMS). The single-dose survival curves for whole crypts were distinguished by extrapolation numbers (3.0, 176 and 1.5 respectively) that were lower than most previously published values for assay by irradiation. Significant sparing of crypts occurred when doses of HN2 or BCNU, but not IMS, were given in 2 equal fractions separated by more than 2 h. Deduced D0 values for those cells from which crypts regenerate were 1.9 mg/kg HN2, 19 mg/kg BCNU and 487 mg/kg IMS.

Alkylating Agents↗
PubMed1977

Metastasis of a transplantable mammary tumour in rats treated with cyclophosphamide and/or irradiation.

We report observations on the spread by metastasis and infiltration of a transplantable tumour in rats treated by 60Co gamma-irradiation of the primary, irradiation plus parenteral cyclophosphamide, or parenteral cyclophosphamide alone. The proportion of animals with overt disseminated disease and the extent of spread were measured with respect to the time elapsed after implantation and treatment of the primary tumour. The incidence of metastatic disease was broadly similar for all treatment groups, but the extent of dissemination was greater in rats whose treatment included cyclophosphamide.

Animals↗
PubMed1977

Serial transplantation, histology and cellular kinetics of a rat adenocarcinoma.

Data are reported on the growth, histology and cell population kinetics of a spontaneous mammary tumour in the rat at the 1st and 35-40th transplantation generation. With serial transplantation subcutaneously in isologous animals, the macroscopic growth characteristics of the tumour did not alter. The tumour had a volume doubling time of approximately 1.6 days at 400 mm3, increasing to about 7 days at 20,000 mm3. The histology, however, changed dramatically from that of a well differentiated papillary adenocarcinoma with a well defined vascular pattern and minimal necrosis to become by the 35th generation a poorly differentiated pleomorphic cellular tumour in which stromal elements and associated vascular supply were minimal and necrosis prominent. These changes were not manifested in the median cycle time of its cells, 16-18 hr, but by an increase in the growth fraction from 0.36 to 0.59 with a commensurate increase in the cell loss factor from 0.04 and 0.30.

Adenocarcinoma, Papillary↗
PubMedDate not supplied

Examination of the correlation of first-week mortality with the gastrointestinal syndrome following chemotherapy.

The equation frequently made between mortality of mammals within the first week after treatment by cytotoxic drugs and the "gastrointestinal syndrome" has been critically examined. Six clinically used drugs were employed. Only for carmustine and 5-FU was a plateau in survival time observed, for increasing single doses. With cyclophosphamide or dactinomycin, mean survival time in the period of interest decreased sharply with dose, in marked contrast to the constancy observed over a large range of doses of radiation. The dynamics of expression of intestinal injury, as judged by mitotic activity in the crypts, was the same for all drugs and for radiation. However, the clonogenic response of the intestine (crypt microcolony assay) differed widely between agents. Cyclophosphamide and dactinomycin did not destroy any crypts at dose ranges containing the 50% lethality dose for mice. Of the remaining four drugs (carmustine, 5-FU, mechlorethamine hydrochloride, and doxorubicin), the surviving fraction of crypts corresponding to 50% lethality of mice varied 17-fold. Altering the route of administration of mechlorethamine hydrochloride from ip to iv increased the lethality dose and the dose for a given level of crypt survival, but not by the same factor. Survival of primitive, clonogenic cells of the bone marrow was also altered, but in the opposite direction. It is concluded that even where mean survival times are closely similar to radiation, the interpretation of the gastrointestinal syndrome following radiation cannot be applied quantitatively in a similar manner after many cytotoxic drugs.

Animals↗
PubMedDate not supplied

Relationships between different measurements of vascularity and clinico-pathological parameters in breast cancer.

Microvascular density has been put forward as an independent prognostic factor in breast cancer, with high levels indicating poorer prognosis. However, various studies have failed to confirm its prognostic value. The reasons for the contradictory results are not known, but it is believed that methodological differences are responsible. To test this hypothesis, we have used four different methods of assessing vascularity (average and highest microvascular density, microvascular volume and image analysis of vascular area) and related them to known prognostic factors in 51 cases of breast cancer NOS. All four methods showed a significant correlation with each other, with the exception of image analysis vs microvascular volume. The average microvascular density was significantly lower in p53 positive compared to negative tumours (median 38.4 and 66.2; IQR 31.1 and 49.4, respectively, p < 0.05). Vascularity, measured by the four methods, was not associated with nodal status or any other parameter examined.

Aged↗