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M M Alsina

Publications and source records attributed to M M Alsina.

11 recordsLinked to original sources
PubMed1991

The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice.

Many human tumors of epithelial origin contain cells overexpressing the epidermal growth factor (EGF) receptor, and there is convincing evidence that cancer cell growth is correlated with the loss of the normal regulation of the EGF receptor signal transduction pathway. Some cancers are clearly dependent on activation of the EGF receptor for their proliferation. Recently, a class of compounds, tyrphostins, which inhibit the protein tyrosine kinase activity of the growth factor receptor, have been described. In this report, we have examined the antiproliferative effects of potent new tyrphostins on a well-characterized human squamous cell carcinoma in vitro and in vivo. We found that two of these compounds (RG-13022 and RG-14620) suppressed not only EGF-stimulated cancer cell proliferation in vitro but also tumor growth in nude mice. RG-13022 also increased the life span of these tumor-bearing nude mice. When administered to tumor-bearing nude mice together with monoclonal antibodies to the EGF receptor at a suboptimal dose which had no effect alone, inhibition of tumor growth was markedly enhanced. These data suggest that tyrphostins have potential as anticancer agents.

Animals↗
PubMed1991

Dependence of a human squamous carcinoma and associated paraneoplastic syndromes on the epidermal growth factor receptor pathway in nude mice.

Increased levels of epidermal growth factor receptor (EGFR) have been shown on squamous cell carcinomas. Recently, we described a squamous cell carcinoma (MH-85) derived from the oral cavity which was associated with several paraneoplastic syndromes including hypercalcemia and cachexia. This tumor induced the same paraneoplastic syndromes in nude mice (BALB/c, nu/nu, male, 4-6 weeks old). Scatchard analysis revealed that there are two classes of EGFR in MH-85. The dissociation constant and number of binding sites for the high affinity receptors were 38 pM and 5 x 10(4)/cell, respectively, and 2.2 nM and 6 x 10(5) cell, respectively, for the low affinity receptors. Growth of MH-85 in culture was stimulated by epidermal growth factor (EGF) and inhibited by monoclonal antibody 108 to human EGFR, which recognizes the extracellular domain of the EGF receptor. Surgical removal of submandibular glands from male nude mice resulted in a dramatic decrease in plasma EGF levels and a significant reduction of tumor growth, hypercalcemia, and cachexia. When EGF (5 micrograms/mouse, every 2 days for 6 weeks, i.p.) was administered to these sialoadenectomized animals, tumor growth increased, with a parallel increase in hypercalcemia. When monoclonal antibody 108 (1 mg/mouse, i.p.) was given 1, 5, and 10 days after MH-85 tumor implantation, tumor formation was retarded, which resulted in delayed onset of hypercalcemia and cachexia. Moreover, when the antibody was injected 6 times in nude mice exhibiting large tumors and profound hypercalcemia and cachexia, there was a striking decrease in tumor growth, which was accompanied with a reversal of hypercalcemia and cachexia. These results indicate that growth of the human squamous cell carcinoma MH-85 is dependent on the EGFR pathway and that subsequent development of hypercalcemia and cachexia is dependent on tumor growth. They also suggest that agents which interfere with the EGFR pathway may have therapeutic potential as anticancer agents in some human tumors.

Animals↗
PubMed1991

Porcine pancreas extract decreases blood-ionized calcium in mice and inhibits osteoclast formation and bone resorption in culture.

Patients with acute pancreatitis commonly manifest hypocalcemia for reasons which are unknown. We found that porcine pancreas extracts (PX) significantly decreased blood-ionized calcium in Balb/c mice. Partially-purified PX with a molecular mass of approximately 27 kDa decreased blood-ionized calcium in the mice. Partially-purified PX suppressed not only 45Ca release from fetal rat long bones which had been stimulated by parathyroid hormone, interleukin-1 alpha, tumor necrosis factor, transforming growth factor-alpha, 1,25-dihydroxyvitamin D3 and prostaglandin E2, but tartrate-resistant acid phosphatase-positive multinucleated cell formation in the presence of 1,25-dihydroxyvitamin D3 in mouse marrow cultures. The results suggest that there is an as yet-unidentified bone metabolism-regulating substance in porcine pancreas which might be responsible for the hypocalcemia associated with acute pancreatitis.

Animals↗
PubMed1991

Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes.

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.

Animals↗
PubMed1991

Differentiation of HL-60 cells into cells with the osteoclast phenotype.

The osteoclast is the unique multinucleated cell that is responsible for bone degradation in both physiological and pathological circumstances. However, knowledge of the lineage of this inaccessible cell, the nature of its precursors, and the regulation of its formation and activation is limited and controversial. Here we show that the human promyelocytic cell line HL-60 has the potential, under the appropriate culture conditions, to differentiate into cells that have morphological and functional characteristics of osteoclasts, including multinucleation, presence of tartrate-resistant acid phosphatase activity, cross-reactivity with monoclonal antibodies that preferentially recognize osteoclasts, and capacity to resorb bone and respond to calcitonin. The multinucleated cells also contain high affinity receptors to calcitonin, in contrast to wild-type undifferentiated HL-60 cells. These data suggest that osteoclasts share a common precursor with hematopoietic cells. These undifferentiated and differentiated HL-60 cells should provide a unique model for study of the cell biology of human osteoclast differentiation, allowing molecular biological and biochemical studies heretofore not possible.

Bone Resorption↗
PubMed1990

[Multiple familial trichodiscoma].

Trichodiscomas are hamartomas of the pilar apparatus, and have been described alone or associated to other benign proliferations of the pilar complex. Two familial cases of trichodiscomas not associated to pilar alterations or systemic manifestations are described.

Adult↗