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Biomedical subjects

L M van Putten

Publications and source records attributed to L M van Putten.

At least 37 records · Page 2Linked to original sources
PubMed1980

Cell kinetic factors, single drugs and combination.

This communication focuses on the problems that exist in the application of cell kinetic information in cancer chemotherapy. From selected historical work, the following conclusions can be drawn. 1) Theoretically optimal drug sequences may fail to show the expected effect. 2) Similar drug sequences cause different effects in different tumors, even when the tumors have similar proliferation characteristics. The unpredictability and the heterogeneity in response make the extrapolation to clinical cancer chemotherapy very difficult. Better prediction may be made from the integration of results from studies combining cell kinetic factors, cellular pharmacokinetics, and biochemistry of drug exposure.

Animals↗
PubMed1979

Adjuvant chemotherapy: theoretical considerations and model studies.

Comparison of response of experimental tumors to adjuvant chemotherapy for minimal disease with the response of solid large tumors to similar drug regimens has indicated that for many tumors the small microscopic foci are more responsive. There are, however, a number of model tumors that respond far less to chemotherapy when applied to minimal disease than when applied to large tumors. The response of these tumors to adjuvant treatment shows similarities with the clinically observed response. The data do not support the hypothesis that the success of a drug combination given as adjuvant chemotherapy may be predicted from the success of the same treatment when applied for manifest disease.

Animals↗
PubMed1979

Vincristine-methotrexate combination chemotherapy and the influence of weight loss on experimental tumour growth.

According to pharmacokinetic reports, vincristine administration should precede methotrexate therapy. Our sequential treatment of L1210 leukaemic mice, in which vincristine was administered before methotrexate therapy, was as effective as treatment with the two drugs given simultaneously. In solid tumour experiments we were unable to show any increase in the antitumour effect of methotrexate when vincristine was injected before methotrexate administration. Consequently, we advocate the re-evaluation of the practice of vincristine leads to methotrexate therapy as used in many clinical protocols for the treatment of patients with osteosarcoma. Pretreatment with vincristine resulted in methotrexate-induced weight loss and sometimes in toxic death of the mice. Since the growth of tumours can be modified by regulation of the caloric intake of the host, this aspect was investigated in more detail. The effect of starvation, which was comparable to the effect of drug-induced weight loss, had a retarding effect on tumour growth. The growth rates of smaller tumour volumes were less severely affected than were those of large tumour masses.

Animals↗
PubMed1978

Misonidazole with small dose fractions in an experimental osteosarcoma.

The mouse osteosarcoma C22LR was irradiated with a single X-ray dose of 1000 or 1500 rad (to prevent rapid growth) and then with fractionated doses of 300 or 600 rad each. Half the mice were given 0.8 mg/g of misonidazole 1 h before irradiation. Tumour growth delay was determined. The radiosensitizer did enhance the effect of small (300 rad) doses per fraction, as well as that of 600 rad doses.

Animals↗
PubMed1978

A morphometrical analysis of lymph node responses to tumors of different immunogenicity.

An immunogenic tumor and a nonimmunogenic tumor were used in C57BL/Ka and CBA/Rij mice, respectively, in a study in which lymph node morphology was quantitatively measured. Lymph nodes were cut in semiseries, and a morphometrical analysis was done on the paracortical and cortical areas as major parts of the active lymph nodes. These parameters could be expressed with confidence in both absolute and relative numbers, since a strong correlation existed between the weight of lymph nodes and the summated surface areas. To determine whether the regional lymph node plays a major role in this response, we performed similar analyses of two nonregional lymph nodes. It was observed that immunogenicity, defined as the ability to evoke an immune response that significantly influences tumor cell take and tumor cell growth, was not relevant in evoking a morphologically evident response. In absolute numbers, the response evoked was strongest in the regional lymph nodes in both systems. However, the percentages of paracortical and cortical areas in the lymph nodes reacting were not essentially different from one node to another during the growth of both tumors. This observation was confirmed by an analysis of variance. These findings suggest that great caution must be exercised when one is interpreting morphological lymph node changes as evidence of an influence of immunological reactions on tumor cell growth.

Adenocarcinoma↗
PubMed1977

Reoxygenation of hypoxic tumour cells.

The present status of our knowledge on the reoxygenation of hypoxic tumour cell during fractionated radiotherapy is reviewed. The phenomenon of reoxygenation does not eliminate the need for studies of hypoxic sensitizers or high LET radiation.

Animals↗
PubMed1976

Biologic activity of two derivatives and six possible metabolites of cyclophosphamide (NSC-26271).

The biologic activity in terms of survival of normal hematopoietic stem, osteosarcoma, and L1210 leukemia cells was determined for the following compounds:cyclophosphamide, its derivatives isophosphamide and trophosphamide, its possible metabolites nor-nitrogen mustard, hydroxylamine mustard, 4-ketocyclophosphamide, and and acrolein, and two substitutes for its primary active metabolite 4-hydroxycyclosphamide anhydro-dimer (4-hydroxy-CP-anhydro-dimer) and 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP). On a molar basis none of the compounds shows a better therapeutic ratio between osteosarcoma and bone marrow stem cells than the parent compound. The therapeutic ratio between L1210 leukemia and normal cells is slightly better for 4-hydroperoxy-CP only. It may be concluded that the conversion of 4-hydroxy-CP-anhydro-dimer and 4-hydroperoxy-CP to the primary active metabolite 4-hydroxycyclophosphamide differs quantitatively. Moreover, it appears that by the use of these precursors a better therapeutic ratio might be obtained for some malignancies but not for others.

Acrolein↗