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Biomedical subjects

A Lage

Publications and source records attributed to A Lage.

At least 37 records · Page 2Linked to original sources
PubMed1988

A new immunotoxin built by linking a hemolytic toxin to a monoclonal antibody specific for immature T lymphocytes.

Hybrid molecules built by conjugation between monoclonal antibodies (MAbs) and toxins are currently being experimentally tested as potential new anti-cancer agents. These immunotoxins have mainly used the plant toxin ricin as the toxic component, which inhibits protein synthesis at the ribosome level. We present an alternative for toxic components using a hemolytic toxin acting at the membrane level, due to its phospholipase activity. The hemolytic toxin (HT), isolated from the sea anemone Stoichactis helianthus, has been conjugated to an antibody towards an antigen expressed on immature T lymphocytes (IOR-T6), by means of an artificial disulphide bridge. The hybrid IOR-T6-HT exhibits no hemolytic activity unless it is reduced. It is toxic for cells (CEM) expressing the IOR-T6 antigen and non-toxic for cells (K562) not bearing the antigen. An excess of unconjugated antibody reverses the toxicity. Immunotoxins based on membrane-active, hemolytic toxins can be a useful alternative when directed towards antigens which do not mediate internalization, as is the case for most carcinoma antigens.

Animals↗
PubMed1987

Factors associated with prognosis in human breast cancer. VII. A comparison between a Cuban and a Swedish study.

Prognosis in human breast cancer is important since therapeutic plans can be adjusted to individual probability of relapse. Comparative studies are not very frequent in literature. Prognostic factors are not assessed in the same way in different countries, thus contradictory results can be obtained. This paper summarizes the studies performed in two different populations of Swedish and Cuban patients. A group of prognostic factors was compared: age, tumor size, lymph node status, hormone receptors and DNA distribution. Some differences were obtained in these parameters and in short-term relapses. Lymph node status was more important in Swedish series, whereas ER content and DNA pattern were of more predictive value in the Cuban series. Biological interpretations of the results is suggested.

Adult↗
PubMed1986

Epidermal growth factor inhibits thymidine incorporation in Ehrlich ascites tumor cells in vivo.

The effects of in vivo injection of epidermal growth factor (EGF) on mice bearing Ehrlich ascites tumors have been studied. Epidermal growth factor was rapidly distributed, reached tumor cells and recognized specific cell membrane receptors. The effects of the subcutaneous injection of EGF were manifested by a decrease of measurable membrane receptors and inhibition of thymidine incorporation to TCA-insoluble material. The effect on thymidine incorporation was dose-dependent and independent on the source (murine or human) of EGF. These results suggest that high doses of EGF could eventually be used for inhibition of the cell proliferation in some tumors.

Animals↗
PubMed1986

Risk factors in mass screening for breast cancer, multivariate analysis of data from the Cuban diagnosis pilot study.

The evolution of mammography has provided possibilities for mass screening programs. Early diagnosis is considered the most important factor in reducing the breast cancer mortality but the mass screening is very expensive if we include all female population. In this paper we show the results of an early diagnosis pilot study with a multivariate data analysis. Data concerning risk factors (age, age at menarche, menopause, parity, age at first childbirth, lactation, abortions and previous benign breast disease) were recorded in 438 patients with breast carcinoma and 1750 patients with benign breast diseases diagnosed in the Early Diagnosis Pilot Program at the National Institute of Oncology and Radiobiology in Cuba. A group of 449 healthy women living in Havana City was also studied. Age and age at first childbirth were the major factor considered. Multivariate data analysis allowed to build stratification trees identifying subgroups with different breast cancer incidence. The usefulness of these stratifications for screening with optimal coverage, sufficiency and efficacy, is discussed.

Adult↗
PubMed1985

Factors associated with prognosis in human breast cancer. V. The simultaneous use of estrogen and progesterone receptor measurements for prediction of short-term relapse.

Prediction of individual fate of breast cancer patients is one of the most important subjects studied because of the heterogeneity of the disease and the possibility of establishment of new therapeutic strategies. Hormone receptors have been recognized to be a valuable tool in prognosis at least in regard to short-term relapse. We have analyzed 400 patients in which hormone receptors has been determined, through stratification techniques, in 18-month and 3-year periods of disease-free interval. Clinical stage was chosen at the most important predictor in the total number of patients, lymph node status was the first predictor, estradiol receptor (ER) automatically was the second one, and the amount of receptor content had an important role in prognosis also. Inside Stage III patients ER should be the first predictor. Remarkable and independent association of progesterone receptor (PgR) content with relapse could be established. Predictive ability of ER and PgR inside lymph node status groups of patients was clearly shown. There was a remarkable difference between polar groups (lymph node-negative, ER+PgR+6% of relapse, and lymph node-positive, ER-PgR-30% of relapse) estrogen receptor status retains its predictive value, at the third year.

Breast Neoplasms↗
PubMed1984

67Ga-citrate distribution in solid hepatoma 22.

The intracellular distribution of 67Ga was studied in solid hepatoma 22 implanted in C3Ha/6 mice and in normal liver tissue from the same animals at different time intervals. The tissues were fractionated according to differential centrifugation principles, and subcellular fractions were isolated consecutively. The enzyme activities and the accumulation of 67Ga were determined in each fraction. The subcellular distribution of 67Ga in the tumor tissue was different compared with normal liver; in tumor it was found mainly in the nuclear fraction and this distribution was independent of time, but in normal liver the accumulation was mainly in the mitochondrial fraction, this was time-dependent and the maximal uptake was found 48 h after 67Ga administration.

Acid Phosphatase↗
PubMed1984

Epidermal growth factor receptors in human breast cancer.

The capacity for specific binding of 125I-epidermal growth factor (EGF) was studied in crude membrane fractions from 95 human breast carcinomas. About 42% of the samples showed saturable, high affinity, specific binding of EGF. In 21% of the tumors we were able to demonstrate high (above 10 fmoles/mg protein) binding capacity. Moreover, high EGF receptor values were associated with a low content of estradiol receptor. These studies are related to the definition of new biochemical markers in human breast cancer.

Animals↗
PubMed1983

Factors associated with prognosis in human breast cancer. III. Estradiol receptors and short term relapse.

Prognosis in breast cancer is one of the most important subjects currently studied because of the heterogeneity of the disease even inside the same clinical stage. Estrogen receptor determination in human breast cancer has been recognized as a prognostic factor since it is related to the long-term survival and disease-free interval. In a series of papers concerning prognosis in breast cancer this the third one which includes estrogen receptor determination in the multivariate analysis, because of the limitations of the clinical factor to conform stratification groups. We have analyzed the short term probability of relapse in a group of 136 patients treated for breast cancer. Multivariate stratification analysis was performed with the aid of Bintree computer program, which produces binary splits of the population according to the criterion of maximal reduction of variance and generates a binary stratification tree. Lymph node involvement is the most important prognostic factor in the probability of relapse. Patients without nodal involvement lacking estradiol receptor had 25% of relapse. It is therefore evident that estradiol receptor is a factor of prognostic value even inside node negative patients.

Breast Neoplasms↗
PubMed1983

Factors associated with prognosis in human breast cancer. IV. Progesterone receptors and clinical factors.

We have found no correlation between progesterone receptor PgR content in human breast tumors and clinical factors associated with the presence of estrogen receptor (ER, age, menopausal status, parity, age at first childbirth, menarche), in spite of the positive correlation between both receptors. Moreover, the association between clinical factors and the percentage of ER(-) PgR(-) tumors were identical to those of ER(-) tumors, but the association between clinical factors and the percentage of ER(+) PgR(-) tumors were inverse to those of ER(-) tumors. That implies that clinical factors associated with the presence of estrogen receptor can not distinguish ER(+) PgR(+) and ER(+) PgR(-) tumors. The stage of the disease is the most important clinical feature in breast cancer patients. In our series the pattern of hormone-receptor was different between Stages I/II and Stage III patients, while the percentage of PgR(+) tumors was constant, a decrease in ER(+) tumors occurred in Stage III patients. In addition similar percentages of ER(+) PgR(+) were found in both groups, but an increase in ER(-) PgR(-) tumors and a decrease in ER(+) PgR(-) tumors occurred in the Stage III patients. Altogether these results suggest that primary loss of progesterone receptors and primary loss of estrogen receptors could be related to different pathogenic mechanisms.

Adult↗
PubMed1983

Early effects of medium change in cultured cells: evidences for the existence of negative modulators of cell proliferation.

Serum deprivation of cells in culture leads usually to an arrest of DNA synthesis and cell proliferation but the transfer of cultured cells from serum-containing to serum-free medium results in a transient stimulation of the incorporation of radioactive thymidine to macromolecules. This stimulation effect produced by medium change can be separated into two different phenomena: a stimulation of thymidine incorporation induced by transfer of cells from conditioned serum-containing medium to fresh serum-containing medium and an additional stimulation induced by transfer of cells from serum-containing medium to serum-free medium. Experimental results indicate that the first effect is probably due to the removal of inhibitors released by the cells even in exponentially growing cultures, and that the second effect is probably due to the removal of inhibitory molecules coexisting in serum with stimulatory factors.

Animals↗
PubMed1983

Factors associated with prognosis in human breast cancer. II. Multivariate stratification analysis.

Prediction of the individual fate of breast cancer patient is one of the most important problems for establishment of therapeutic plans. We have analyzed the relationships of clinical factors to 3-year and 8-year survivals in a series of 400 patients treated for breast carcinoma. Multivariate stratification analysis for obtaining subgroups with different survivals was performed with the aid of Bintree, a computer program which produces binary splits of a population according to the criterion of maximal reduction of variance, and generates a binary stratification tree. Lymph node status was the major predictor for both short and long term prognosis but had no important role in the survival of patients who relapsed. Antecedent abortions were related to less relapses. Age, previous benign breast diseases, nulliparity and lactation conditioned better prognosis without association with relapse probability, indicating an association with the speed of evolution of the disseminated disease. In general clinical data were insufficient for establishment of good and bad prognosis polar groups of patients, especially in patients in which no clinical lymph node involvement was recorded.

Adult↗
PubMed1983

Factors associated with prognosis in human breast cancer. I. Predictors for rate of evolution and relapse.

The associations of several clinical factors with general survival, percentage of relapse and survival in the group of patients who relapsed were analyzed in a series of 399 Stage II breast cancer patients operated and irradiated at the Institute of Oncology and Radiobiology in Havana. In another series of 187 patients these associations were studied in regard to the presence of estradiol receptors in the tumors. Factors related to the presence of estrogen receptors were unrelated to the percentage of relapse in long term follow-up. Age and menstrual status were related to the presence of estradiol receptors and to survival inside the group of patients who relapsed but were unrelated to the percentage of relapses. Lymph node status was mainly associated with the percentage of relapses but not related to the presence of estradiol receptors. Other factors (parity and age at first childbirth), related to the presence of receptors, did not clearly influence prognosis. Lactation influenced positively survival inside the relapse group without any clear association with hormone receptors. Results are discussed in terms of a model considering particular host--tumor interaction: The probability of relapse and the speed of evolution of the systemic disease, mutually independent, but determining the prognosis.

Adult↗
PubMed1982

Ureteral replacement with a new synthetic material: Gore-Tex.

There are no currently accepted synthetic ureteral substitutes. When faced with the need for ureteral replacement, the urologist must resort to pedicle grafts of intestine or bladder. Based on encouraging preliminary work in Europe, we have used a new synthetic vascular substitute, Gore-Tex, to replace segments of ureter in the dog. This material is made of expanded (microporous) polytetrafluoroethylene. In vascular surgery it is currently the preferred material due to its non-wetting and non-clotting surface when used in the arterial and venous beds. Adult mongrel dogs underwent segmental replacement of the right ureter and subtotal replacement of the left ureter with segments of 5-mm. tubed Gore-Tex. All anastomoses were performed with running 6--0 prolene. Antibiotics were given routinely perioperatively. Data on 7 dogs are available. Results indicate that Gore-Tex is well tolerated as a ureteral substitute to bridge gaps between segments of ureter. Anastomoses of Gore-Tex to bladder were not successful, resulting in infection and migration of the prosthesis. Under proper circumstances, Gore-Tex can be a useful potential addition to the urologic armamentarium.

Animals↗
PubMed1982

Effect of two antiproteinases on the growth of transplantable tumors and the proliferation of untransformed and transformed cells in culture.

The paper reports on the experiments carried out for the evaluation of the effect of two antiproteinases, aprotinin, and epsilon-amino caproic acid (EACA), on several transplantable tumors and cells in culture. It was demonstrated that aprotinin has a preferential therapeutic effect on the solid form of L1210, in comparison with its ascitic form. Treatment with aprotinin of Lewis lung carcinoma, Melanoma B16, and Hepatoma 22, in a limited chronic time schedule 1-9, and 1-11 brought no significant increase in survival; positive therapeutic effects had been shown for the first and the last of the tumors mentioned with life-time injections of the drug. Moreover, aprotinin treatment increased the number of lung nodules for the Lewis lung carcinoma inoculated either subcutaneously or intravenously. EACA applied same schedule had no effect on the survival of tumor-bearing animals. These data are discussed in terms of their relevance to antiproteinase therapy in human cancer. No selective inhibition of proliferation for more tumorigenic cell culture lines of spontaneous and viral origin was demonstrated after treatment with both compounds.

Aminocaproates↗
PubMed1982

Experimental approach for the search of effective drug combination in cancer chemotherapy.

A comparative assay of cytostatic combinations was carried out in a number of transplantable mouse tumors: L1210, Lewis lung carcinoma, Sarcoma 180 and others. The results suggest that the combination cyclophosphamide (CPH) plus procarbazine (PROC) enhances the antitumoral activity in comparison with monochemotherapy. The combination CPH + PROC can be used as basis for the elaboration of more effective polychemotherapy schemes. Combination of CPH + PROC + Prospidine and CPH + PROC + CCNU resulted in enhancement of the treatment effect in experimental tumors.

Adenocarcinoma↗
PubMed1982

Neoplastic progression evidenced in the L929 cell system. I. Selection of tumorigenic and metastasizing cell variants.

Starting with a L929 cell strain of low tumorigenicity, and through in vivo and combined in vivo--in vitro manipulation, we have isolated a number of related culture cell lines with different tumorigenicity and metastasis ability in C3HA/H mice. Within our system, tumorigenicity can be greatly enhanced without the simultaneous development of metastasis ability, the latter arising only after long-term in vivo serial transplantation. Metastatic variants express better the ability to undergo to cascade of metastasis than the primary tumor. The selection of metastatic variants from a tumor, using its subcutaneous inoculation, renders cell lines with different behavior. Finally, viable cells are recovered from lungs of animals inoculated with metastatic variants that would not be expected to show true metastatic foci; the results are commented in relation to the phenomenon of metastasis dormancy. Our experiments are discussed under the scope of the hypothesis of neoplastic progression as a multistep process.

Animals↗
PubMed1982

Neoplastic progression evidenced in the L929 cell system. II. In vitro growth properties and biochemical characteristics of cell variants with different malignant behavior.

Using a culture cell system, derived from a low-tumorigenic strain of L929 mouse fibroblasts, including cell variants with different malignant behavior in vivo, we have tried to dissociate a group of biological and biochemical transformation-associated properties with respect to the process of neoplastic progression. It is shown that morphologic changes, nonalignment in vitro, and growth in soft-agar are not sufficient alterations for in vivo malignant behavior and, also, not useful indicators for further neoplastic progression. The rate of hexose uptake should also be considered as unrelated to this process. The increase in tumorigenicity, but without the concomitant development of metastasis ability of the cells, was associated with the decrease of a 160k cell surface protein and the diminution of the tumor dose 50%. Finally, further alteration in morphology and the appearance of a 177k cell surface protein were associated with the development of metastasis ability, in an early stage; loss of fibronectin and the ability to grow as macrocolonies in increasing concentrations of deoxyglucose appeared as associated to more advanced stages of neoplastic progression. On the whole, the approach of taking the in vivo behavior, and not the in vitro properties, as end-point for the study of transformation is recommended on the basis of this and a previous paper.

Animals↗