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I P Witz

Publications and source records attributed to I P Witz.

At least 19 recordsLinked to original sources
PubMed1992

In vivo tumorigenicity and in vitro sensitivity to tumor-necrosis-factor alpha mediated killing of c-Ha-ras-transformed cells.

Cellular subclones of high and low tumorigenicity obtained from a mouse c-Ha-ras-transformed clone, were examined for their sensitivity to tumor-necrosis-factor (TNF)-mediated cytotoxicity. Cells of the highly tumorigenic subclones showed a significantly enhanced resistance to the cytotoxic effect of TNF plus cyclohexamide (CHI) as compared to cells of the low-tumorigenic subclones. The enhanced resistance to TNF+CHI was not due to a lower expression of TNF receptors on the cells. The c-Ha-ras-transfected cells were transformed and maintained in culture only (C cells). In vivo passage of cells of the initially low-tumorigenic c-Ha-ras subclones through the mouse significantly enhanced the tumorigenic potential of these CTC cells (culture/tumor/culture). In correlation with their enhanced tumorigenicity, the CTC cells were highly resistant to TNF-mediated cytotoxicity as compared to C cells of the same subclone. Furthermore, the involvement of TNF in determining the tumorigenic phenotype of the c-Ha-ras-transformed cells was demonstrated in a more direct manner. Cells of a c-Ha-ras-transformed low-tumorigenic, highly TNF-sensitive subclone were selected by repeated cycles of in vitro exposure to TNF alpha. As a result, a stable, highly TNF-resistant population of cells emerged. These TNF-resistant cells caused more tumors in mice as compared to their original TNF-sensitive cells. These results show that the resistance to the cytotoxic effect of TNF plus cyclohexamide may be involved, at least partially, in the tumorigenic potential of c-Ha-ras-transformed cells and suggest a possible role for TNF in the enhancement of the tumorigenic potential of these cells in mice.

3T3 Cells↗
PubMed1992

FcR may function as a progression factor of nonlymphoid tumors.

Tumor progression is a multistep process involving genetic and epigenetic changes in a transformed clone. Some of these changes may be induced by host factors which may also select for transformed cellular variants with a high ability to survive and propagate. In this article we review studies showing that receptors for the Fc portion of IgG may be expressed on cells from human or animal tumors of nonlymphoid origin. We also review data demonstrating that at least with respect to cells transformed in vitro with Polyoma virus, transformation per se is not sufficient for the induction of Fc receptor expression. We also summarize preliminary data showing that Fc receptor expression is causally involved in conferring a high malignancy phenotype upon transformed cells. Possible mechanisms to explain these observations are discussed.

Animals↗
PubMed1992

Phenotypic properties of 3T3 cells transformed in vitro with polyoma virus and passaged once in syngeneic animals.

Cloned BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) acquired a higher tumorigenicity phenotype after a single in vivo passage. Some of the in vivo passaged cells (CTC cells) exhibited also a higher metastatic phenotype than cells from the same clones that were maintained only in culture (C cells). A phenotypic comparison between CTC and C cells was performed. It was found that most CTC lines exhibited a higher binding to laminin compared to their clonal C cell ancestors. Some CTC cells were less sensitive to the cytotoxic effects of TNF-alpha than the corresponding C cells. CTC cells originating from tumors which appeared after a long latency period (late tumors) tended to express Fc gamma RII while CTC cells originating from tumors which appeared after a short latency period (early tumors) as well as the corresponding C cells tended not to express Fc gamma RII. The expression of a membrane epitope recognized by a monoclonal antibody expressing specificity towards PyV transformed cells, was down-regulated on late tumor cells compared to early tumor cells. Transfection of cloned PyV-transformed BALB/c 3T3 cells with the beta 1Fc gamma RII gene augmented the tumorigenicity and metastatic phenotype of the transfectants compared to control transfectants.

3T3 Cells↗
PubMed1992

Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.

3T3 Cells↗
PubMed1991

In vivo acquisition of Fc gamma RII expression on polyoma virus-transformed cells derived from tumors of long latency.

BALB/c 3T3 cells transformed in vitro with polyoma virus were cloned and passaged once in syngeneic mice. Resulting tumors from each clone were explanted and recultured. Expression of receptor for Fc of IgG (Fc gamma RII) in the original in vitro maintained clones and in cells derived from tumors elicited by the respective cells was measured at the protein level as well as at the mRNA level. Clones were assayed in pairs. The ancestor in vitro maintained clones [designated cultured cells (C)] were compared with cells derived from the same clones after a single passage in vivo followed by explantation and reculturing [designated cultured-tumor-cultured cells (CTC)]. C cells of any of the tested clones did not express Fc gamma RII. On the other hand, certain CTC cells were positive. The Fc gamma RII-positive cells were derived from tumors appearing after a long precancer latency period (greater than 140 days). CTC cells derived from tumors that appeared after shorter latency periods (less than 80 days) were Fc gamma RII negative. These results were obtained both by using radioimmunoassay and monoclonal antibodies against mouse Fc gamma RII as well as by Northern blot analysis using the Fc gamma RII complementary DNA probe. The involvement of macrophages as the Fc gamma RII-expressing cells in CTC cells was excluded. Fc gamma RII expression was down-regulated in CTC cells as a function of time following their explantation into culture. Fc gamma RII expression could be up-regulated in these cells and induced on C cells by maintaining the cultured cells in the presence of normal mouse serum or recombinant interferon. We also tested the expression of Fc gamma RII on CTC cells following their inoculation into syngeneic mice for a second time (CTCx2 cells). The results showed a positive correlation between Fc gamma RII expression in the inoculated ancestor CTC cells and on the CTCx2 cell progeny.

Animals↗
PubMed1991

The relationship between in vitro fertilization and naturally occurring antibodies: evidence for increased production of antiphospholipid autoantibodies.

OBJECTIVE: Assessment of possible effects of ovarian stimulation during in vitro fertilization (IVF) treatment cycles on circulating levels of antiphospholipid and antinuclear autoantibodies. DESIGN: The study was performed prospectively. Sera were obtained at three time points along IVF treatment cycle. Levels of autoantibodies directed against nuclear components, mitochondrial antigens, and phospholipids were determined using enzyme-linked immunosorbent assay. PATIENTS: Thirty-five patients, who underwent at least one previous IVF attempt, and 36 age- and sex-matched controls were analyzed. All participants were randomly selected. RESULTS: The mean levels of antiphospholipid (but not antinuclear) autoantibodies in sera from IVF-treated patients were found to be significantly higher than the corresponding values of the control group (for immunoglobulin [Ig]M isotype: anticardiolipin, antiphosphatidyl L-serine; for IgG isotype: anticardiolipin, antiphosphatidyl L-serine, and antiphosphatidylcholine; P less than 0.0001, assessed by Mann-Whitney test). The autoantibody levels remained more or less constant at different time points along the treatment cycle. No correlation with age and number of previous IVF cycles was demonstrated. CONCLUSIONS: Serum levels of antiphospholipid (but not antinuclear) autoantibodies increase after IVF treatment. Based on these preliminary data, it is not yet possible to estimate if the observed changes in autoantibody levels might have any future clinical influence on infertile patients undergoing IVF treatment.

Adult↗
PubMed1991

CD5+ B cells and naturally occurring autoantibodies in cancer patients.

We have determined the percentage of CD5+ B lymphocytes in the peripheral blood of cancer patients and healthy controls, using antibodies directed at the CD5 and CD19 (pan-B) markers. The frequencies of CD5+ B cells, expressed as a percentage of total B cells, ranged from 14.3 to 57.5% in the controls and from 14.8 to 82.8% in the patient population. One-third of the cancer patients had frequencies greater than 2 s.d. above the mean of the control population. The CD5+ B cell fraction expressed as a percentage of total lymphocytes was also significantly elevated in this group of cancer patients. These results suggest that the CD5+ B cell compartment may be affected by the malignant process or by the therapy modality employed. The plasma levels of several naturally occurring autoantibodies, the products of the CD5+ B cells, were also assessed in cancer patients and controls. No significant differences were observed when reactivity to several autoantigens was measured. These included nuclear components and phospholipids.

Adolescent↗
PubMed1990

Some cellular and molecular characteristics of high and low tumorigenicity variants of polyoma-virus transformed cells.

We analyzed several cellular and molecular properties of BALB/c 3T3 cellular clones transformed in vitro with polyoma virus and exhibiting a high or low tumorigenicity phenotype. We also analyzed the same clones after a single in vivo passage in syngeneic mice. This passage invariably induced and/or selected variants exhibiting a very high tumorigenicity phenotype. BALB/c mice bearing tumors induced by the inoculation of the above cells, regardless of their tumorigenicity phenotype, have a lower number of L3T4 positive splenocytes than appropriate controls. The response to Con-A of spleen cells from such mice was also suppressed. Concomitantly, an increase in Mac-1 positive splenocytes could be measured. In spite of the non-specific suppression of T cells, spleen cells from tumor-bearers showed a specific proliferative response to polyoma antigens. Molecular analysis of polyoma transformed cells showed no differences between the various cells with respect to integration of the polyoma viral genes or with respect to src, myc and fos proto-oncogenes. In vitro maintained cells and in vivo passaged cells seemed to differ, however, in the content of polyoma middle T. Whereas polyoma virus transformed cells maintained only in culture never expressed low affinity receptors for IgG (Fc gamma RII), certain in vivo passaged cells did. This expression could be measured both at the protein and the mRNA level. Those in vivo passaged cells which expressed F alpha RII gave tumors following a long latency period. Ongoing experiments will indicate whether or not Fc gamma RII expression is linked to long latency of tumor development.

Animals↗
PubMed1989

Differential tumorigenicity of 3T3 cells transformed in vitro with polyoma virus and in vivo selection for high tumorigenicity.

BALB/c 3T3 cells transformed in vitro with a temperature-sensitive mutant of polyoma virus were cloned. Forty-eight clones examined demonstrated heterogeneity with respect to doubling-time in vitro and tumorigenicity in syngeneic mice in vivo. Observation periods that lasted in certain cases as long as 2 years showed that some clones exhibited a relatively high tumorigenicity, i.e., they yielded a relatively high incidence of tumors following a small inoculum of cells and a relatively short latency period. Other clones were relatively low tumorigenic: even high tumor cell inocula yielded a relatively low tumor incidence following a relatively long latency period. These results indicate that at least in this system variation in tumorigenicity is generated independently of host factors. An intraclonal heterogeneity with respect to the length of the precancer latency period was seen. Some tumors appeared relatively early following inoculation of cloned cells, whereas others appeared considerably later following an identical inoculum of the same clone. Cloned in vitro transformed cells were passaged once in syngeneic mice and recultured. The single in vivo passage cycle augmented considerably the tumorigenicity of these cells as compared to their in vitro maintained clonal ancestors. The increased tumorigenicity of the in vivo passaged cells is due, most probably, to the in vivo induction and/or selection of high tumorigenic intraclonal variants. The survival time of mice bearing high tumorigenicity variants was very similar to that of mice bearing low tumorigenicity variants.

Animals↗
PubMed1988

Further studies on the determinant recognized by naturally-occurring murine autoantibodies reacting with bromelain-treated erythrocytes.

Radioimmunoassays (RIA) have confirmed previous studies that trimethylammonium (TMA) or its derivatives constitute part of the determinant recognized by naturally-occurring antibodies (NOA) with the ability to interact with bromelain-treated mouse erythrocytes (BrMRBC). Further studies on this determinant revealed its presence on erythrocytes from several species in addition to mice. In most cases (except in chickens) the determinant was cryptic and could be exposed only after proteolytic treatment of the erythrocytes. The determinant was also found on certain murine lymphoma cells. We also found that bromelain was not the only enzyme that could be used to expose the determinant. Papain, but not trypsin, was able to unmask the determinant on mouse erythrocytes. Rabbit antibodies directed against the idiotypes of four different monoclonal BrMRBC-binding NOA were prepared. Direct RIA assays and inhibition assays showed that the different monoclonal BrMRBC-binding NOA shared a common idiotype specific to such antibodies. The common idiotype was detected in the serum from several mouse strains and in wild mice.

Animals↗
PubMed1979

Placenta-bound immunoglobulins.

Low pH eluates were prepared from trophoblasts derived from 8 term human placentas. A qualitative analysis for immunoglobulins revealed the presence of IgG, IgA, and IgM in these eluates. IgC-rich fractions were obtained by DEAE-cellulose chromatography of ammonium sulfate-concentrated eluates. These fractions were able to neutralize, in vitro, the catalytic activity of reverse transcriptases (RT) from several retroviruses. RT from baboon endogenous virus (BEV) seemed to be more susceptible to the neutralizing activity of some eluates. This was in contrast to RT from feline leukemia virus (FeLV) which were neutralized by eluates of leukocytes from chronic myelogenous leukemia. In contrast to previous and present results with purified IgG from leukemic leukocytes, the purified IgG from placenta eluates was incapable of RT neutralization. However, such purified IgG fractions inhibited mixed lymphocyte reactions.

Female↗