[Comparison of thymidylate synthase properties isolated from the rat tapeworm, hymenolepis diminuta, with properties of enzyme isolated from the host in regenerating rat liver]. / Porównanie wlasciwosci syntazy tymidylanowej oczyszczonej z tasiemca szczurzego, Hymenolepis diminuta, z wlasciwosciami enzymu zywiciela wyizolowanego z regenerujacej watroby szczura.

Thymidylate synthases (TS) from the tapeworm, Hymenolepis diminuta, and regenerating rat liver have been purified by means of affinity chromatography on immobilized 10-formyl-5,8-dideazafolate and concentrated on immobilized p-aminophenyl-5-fluoro-2'-deoxyuridine monophosphate. Molecular weights of native TS from the tapeworm and regenerating rat liver were 62 kD and 81.5 kD, respectively, and molecular weights of the monomers were 34.4 kD and 34.9 kD, respectively, pointing to dimeric structures of both enzymes. The dependence of TS activity on temperature (Arrhenius plot) was biphasic for the parasite enzyme, with lower activation energy above 32 degrees C, and monophasic for the host enzyme. 2'-deoxyuridine-5'-monophosphate (dUMP) analogues, 5-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP), 2-tio-5-FdUMP,N4-hydroxy-2'-deoxycytidine-5'-monophosphate (N4-hydroxy-dCMP) and N4-hydroxy-5-FdCMP, were competitive with respect to dUMP, slow-binding inhibitors of TS from both sources, with K1 values in 10(-6)-10(-9) M range. 5-FdUMP was distinctly stronger inhibitor of the host than the tapeworm TS, whereas N4-hydroksy-5-FdCMP inhibited stronger the parasite enzyme. Interaction of 5,10-methylenetetrahydrofolate (CH2H4PteGlu) analogue, 10-propargyl-5,8-dideazafolate (pddPteGlu), and its di- and triglutamates with both enzymes were studied. Inhibition of the parasite and host enzymes by pddPteGlu was of mixed-type with respect to CH2H4PteGlu, with K1 values in 10(-8) M range. Introduction of additional glutamate residues changed inhibition type to noncompetitive with respect to Ch2H4PteGlu and lowered K1 values (pddPteGlu3 < pddPteGlu2 < pddPteGlu1).(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities.

Results of a prospective randomized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported. Five-hundred-fifty-three Stage I patients whose limbs were affected entered the study; 267 were submitted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinically positive nodes were detected. Survival curves of the two treatment groups could be superimposed. No subsets of patients benefitted from immediate node dissection. The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months. If the quarterly follow-up is not guaranteed, immediate node dissection is advisable, at least for melanomas thicker than 2 mm.

Investigation of immunoglobulins, circulating immune complexes and plasma free hemoglobin in cancer patients on 60Co gamma-ray therapy.

32 patients with different tumours were irradiated by 60Co gamma-rays. During therapy lasting for several weeks, changes in the content of immunoglobulin and of some other serum proteins, circulating immune complexes and plasma free hemoglobin were determined. Immunosuppression according to immunoglobulin content in serum was not produced by this type of radiation. Decrease in immune complex levels was a good prognostic sign. Low values of plasma hemoglobin content during treatment indicated that no erythrocyte membrane damage had been effected.

Stage I melanoma of the limbs. Immediate versus delayed node dissection.

553 patients with stage I malignant melanoma of the limbs entered a prospective randomized clinical trial carried out by the W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to January 1974. 286 patients were submitted to wide excision of primary and node dissection at the time as appearance of regional lymph node metastases and 267 to wide excision and immediate node dissection. Survival was identical in the 2 groups. Different subsets of patients were evaluated to assess whether some groups of patients may benefit from immediate node dissection. As regards sex, females and a significantly higher survival rate than males (p < 0.05), but results were not improved by immediate node dissection. Maximum diameter and elevation of primary melanoma were significantly related to survival but also in these cases immediate node dissection did not achieve better results. 63 patients had an excisional biopsy of their melanoma within 4 weeks before final treatment. This procedure did not worsen survival and also in this case immediate node dissection did not improve survival. 273 cases were classified according to histologic type: survival of superficial spreading and nodular melanoma was not different at a statistically significant level after the 2 treatment modalities. 325 cases were considered classifiable according to Clark's levels, out of these 165 were submitted to immediate node dissection. Neither level III nor level IV cases showed higher survival rate after immediate node dissection. Maximum tumor thickness according to Breslow was evaluated in 338 cases: 188 were submitted to wide excision and immediate node dissection. In no clusters of thickness did the enlarged surgical procedure achieve better results. The authors conclude that there is good evidence that in stage I melanoma of the extremities delayed dissection.

Investigation of a valuable biochemical indicator in radiotherapy. III. Serum lactate dehydrogenase enzyme level on irradiation of cancer patients.

In search of a valuable indicator of the effects of radiotherapy, the immune answer, leucocyte number, plasma free hemoglobin and serum haptoglobins were studied [3, 7]. Among the enzymes of interest, lactate dehydrogenase (LDH) was chosen for measurements, as it gave significantly elevated values on irradiation of blood, in vitro [6]. In the present study LDH values are shown on irradiation of cancer patients by differing types of radiation sources during treatment for several weeks. In 63% of the cases increase in respect of the untreated control was observed, and this was manifested during 4 or 5 weeks' treatment. "Modern beams", as high-energy X-ray and electron-ray increased LDH enzyme values less than conventional 200-kV X-rays and 60Co-gamma-rays. In the study of LDH isoenzymes, components 4 and 5 gave elevated values, others remained unchanged. Correlation between LDH enzyme and plasma free hemoglobin was estimated.

Investigation of a valuable biochemical indicator in radiotherapy. I. Immunological tests and reticulocyte number.

Patients with different cancers were treated by 200-kV X-rays, high-energy X-rays and 60Co-gamma rays. Changes in the immunoglobulin level were observed by immunoelectrophoresis qualitatively and by immunodiffusion quantitatively. Reticulocyte count was made in smears. It was concluded that immunoelectrophoresis was only of limited value in the investigation of a biochemical indicator in radiotherapy; immunodiffusion was more promising. Slight immunosuppressive tendency and return to the control level was observed during treatment. An increase in reticulocyte number during radiotherapy seems to be a good prospect in evaluating the effectivity of the treatment.

Changes of blood components on in vitro and in vivo irradiation in cancer therapy.

In vivo irradiation of the blood followed by a local or parenteral injection with irradiated blood is a useful tool in radiotherapy. To reveal changes in the components of irradiated blood, the serum enzymes LDH, GOT and GPT were examined in the blood of healthy donors, and cancer patients. The same enzymes were determined in the blood of in vivo radiation-treated patients. It seems that with some restrictions LDH offers a possibility to be regarded as biological indicator of radiation effects. Beside enzyme determinations blood picture was taken and immunological methods were used too, to check their usefulness in the evaluation of radiotherapy.

[Study of the biochemical and radiochemical effects of the agent MTDQ (author's transl]. / Beitrag zu den bio- und radiochemischen Wirkungen der Verbindung MTDQ.

The antioxidant MTDQ exhibits a radiosensitizing effect and was used in pretreatment of radiation-resistant human tumors, e.g. synoviomas, sarcomas, von Recklinghausen disease. After this premedication and fractionated radiation therapy of different kinds a permanent regression of the tumors was observed. The radiosensitizing compound is non-toxic and selectively accumulates in tumorous tissues. The chemical structure (three functional groups) and in vitro tests make probable that the main factors in the mechanism of action are peroxide decomposition, hydrol formation, polymerization and, in the course of those reactions, the in situ release of oxygen.

Inefficacy of immediate node dissection in stage 1 melanoma of the limbs.

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.