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Biomedical subjects

M Inbar

Publications and source records attributed to M Inbar.

140 records · Page 8Linked to original sources

A specific metabolic activity on the surface membrane in malignant cell-transformation.

The carbohydrate-binding protein, Concanavalin A (Con A), binds to glucose- or mannose-like sites on the cell-surface membrane. Unless the cells are treated with trypsin, this protein agglutinates malignantly transformed cells, but not normal cells. The transformed cells were agglutinated at 24 degrees C but not at 4 degrees C. Transformed and normal cells treated with trypsin were agglutinated at both 24 degrees C and 4 degrees C with high concentrations of Con A (500 mug/ml), but only at 24 degrees C with low concentrations (5 mug/ml). The same number of Con A molecules were bound to normal and transformed cells at both temperatures. The results indicate that the site for Con A on the surface membrane contains two activities, a component that binds Con A molecules (B) and a component that determines agglutination (A). B is not temperature sensitive and is active in normal and transformed cells, whereas A, which is temperature sensitive, is in an active form only in transformed cells. A can be activated by trypsin, and the increased activity per cell allows agglutination at 4 degrees C with a high, but not with a low, concentration of Con A. Agglutination of transformed cells by wheat-germ agglutinin, which binds to N-acetyl-D-glucosamine-like sites, and by soybean agglutinin, which binds to N-acetyl-D-galactosamine-like sites, was not temperature sensitive. Thus, the temperature-sensitive component A is specific for Con A, and malignant transformation of normal cells, which results in agglutinability by Con A, is associated with the activation of a specific temperature-sensitive activity on the surface membrane.

Agglutination Tests↗

Interaction of the carbohydrate-binding protein concanavalin A with normal and transformed cells.

It has been shown that the carbohydrate-binding protein concanavalin A (ConA) can agglutinate leukemic cells and cells transformed by polyoma virus, simian virus 40, chemical carcinogens, and X-irradiation. This protein did not agglutinate normal cells under the same conditions. The agglutination was reversed by competition with alpha-methyl-D-glucopyranoside (alpha-MG), a carbohydrate that strongly binds to ConA, but not by the carbohydrates alpha-methyl-L-fucopyranoside or N-acetylglucosamine, with no binding or weak binding to ConA. Destruction of the alpha-MG binding sites of the native protein by removal of bivalent metal ions abolished the agglutination produced by the native protein. The treatment of cells with trypsin resulted in the agglutination of normal cells by ConA and a decrease of agglutinability of transformed cells. When nonagglutinating untransformed 3T3 cells were infected with simian virus 40 and normal rat cells were infected with polyoma virus, the infected cells became agglutinable several days after virus infection. The percentage of cells agglutinated, about 50 per cent, was much higher than the percentage of cells hereditarily transformed. The results indicate that the surface membrane of transformed cells contains sites that interact with the alpha-MG binding sites of ConA, that such sites can be found on the surface membrane of normal cells after treatment with trypsin, and that the change in the surface structure from normal to transformed occurs in cells that are abortively transformed.

Agglutination↗

Prognostic importance of advanced age in aggressive non-Hodgkin's malignant lymphoma.

The importance of age as a prognostic factor in aggressive non-Hodgkin's malignant lymphoma (NHL) remains controversial. It is not clear whether age is an independent factor, reflecting the limited physiologic reserves of the patient, and leading in any treatment conditions to the poorer treatment outcome. This study was aimed at assessing the influence of age on treatment results in NHL patients. Therefore, the records of 40 patients with histologically confirmed NHL of intermediate and high-grade malignancy, according to the Working Formulation, who were treated by Adriamycin-containing chemotherapy, were retrospectively reviewed. There were 25 patients above 60 years of age and 15 patients below this age. Myelotoxicity was observed in 60% of the patients in the younger and in 48% patients in the older age group. The median time to dose-limiting toxicity, average percentage of projected dose intensity for all drugs, and percentage of projected dose intensity did not differ significantly in the two groups. Complete remissions (CR) were obtained in 67 and 64% of the younger and older groups, respectively. Progressive disease was observed during the treatment in 20% of the patients in each age group. Median survival was 36.5 and 32 months in the younger and older group, respectively. In conclusion, age alone is not an absolute predictor of survival of treated elderly patients with aggressive NHL. Dose rate, tolerance of treatment and achievement of CR are additional important prognostic factors. Dose intensity should not be automatically reduced at the beginning of the treatment, especially now that growth factors are available.

Adult↗

Vascular invasion in high grade sarcoma of the extremity is associated with short overall survival.

Intravascular sarcoma thrombi were histologically evident in 2% of 470 patients with soft tissue or bone sarcoma treated during the last 3 years. Vascular invasion by sarcoma in our series was associated with an aggressive disease and short-term overall survival. In all the cases there was a large or locally advanced primary high grade sarcoma, and in all but one case, where preoperative chemotherapy was administered, the response was far from satisfactory. The post-operative course in 70% of the patients was characterized by early systemic spread, and a median overall survival of 9.5 months. The gloomy prognosis of our patients does not necessarily stem only from the presence of vascular invasion, but may also be related to other factors as histologic grade and tumor size. However, as compared to similar cases in our patient population, which did not show vascular invasion, the course here was more violent and short.

Adolescent↗

Adriamycin-ifosfamide induction chemotherapy for extremity soft tissue sarcoma: comparison of two non-randomized protocols.

Chemotherapeutic cytoreduction of soft tissue sarcomas may permit less radical operation. In cases of large or multi-compartmental masses, deeply seated tumors or involvement of a neurovascular bundle, down-sizing of the mass is required before limb sparing surgery can be considered. We have applied a combination chemotherapy consisting of intravenous adriamycin and ifosfamide with intra-arterial cisplatin for patients with soft tissue sarcomas of the extremity as induction treatment, and switched to an intravenous-only protocol due to toxicity and management difficulties. Adjuvant chemotherapy and radiation therapy were given after limb-sparing surgery in both regimens. Fresh tumor specimens were obtained and were examined for tumor size, surgical margins, percent of necrosis, evidence of vascular or perineural invasion, and the presence of Pgp, Ki-67, p53, PCNA and bcl-2-oncoprotein. Our results in terms of percentage of tumor necrosis were comparable and even better in favor of the second regimen [38% good histological response with intravenous (i.v.)-only versus 12.5% for combined i.v. + intra-arterial (i.a.]. The clinical and radiological responses were also better for the second (i.v. only) regimen (45%) than for the first (i.v. + i.a.) regimen (12.5%). The toxicity and the inconvenience to the patients and to the treating staff were greater in the first regimen that combined intra-arterial and intravenous infusions. In the first group the failure rate is 75% within 32 months of follow-up, while it is 33% within 12 months follow-up in the second group. The immunohistochemical markers did not correlate with disease control nor with the patient outcome. Intravenous administration of ADR-IFX induction chemotherapy was more feasible than combined i.v. ADR-IFX plus i.a. cisplatin and achieved better results.

Adult↗