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I Avis

Publications and source records attributed to I Avis.

35 records · Page 2Linked to original sources
PubMed1991

[Psi 13,14] bombesin analogues inhibit growth of small cell lung cancerin vitro and in vivo.

Bombesin/gastrin releasing peptide (BN/GRP) functions as an autocrine growth factor in small cell lung cancer (SCLC). Previously, this autocrine growth cycle was disrupted by a monoclonal antibody which binds to the carboxyl terminal of BN and neutralizes the peptide so that it is unable to interact with the BN/GRP receptor. Here a series of BN analogues were synthesized which have a reduced peptide bond near the carboxyl terminal. The analogues inhibited specific binding of 125I-GRP to SCLC cell line NCI-H345 in a dose-dependent manner and the analogue [D-Nal6, Psi13,14, Phe14] BN6-14 was approximately 6-fold more potent than was (Psi13,14, Leu14)BN with a 50% inhibition concentration value of 5 nM. [DNal6, Psi13,14, Phe14]BN6-14 and [Psi13,14, Leu14]BN had no effect on the cytosolic Ca2+ levels but antagonized the increase in cytosolic Ca2+ caused by 10 nM BN. [Psi13,14, Leu14]BN (1 microM) inhibited the growth of SCLC in vitro using a clonogenic assay by approximately 70% Also, injection of [Psi13,14, Leu14]BN (10 micrograms, s.c.) inhibited the growth of SCLC xenografts in nude mice in vivo by approximately 50%. These data suggest that the autocrine growth cycle of BN/GRP in SCLC may also be disrupted by peptide antagonists which bind to the BN receptor.

Animals↗
PubMed1991

Alpha-amidation of peptide hormones in lung cancer.

Small-cell lung cancer (SCLC), the most common neuroendocrine tumor in humans, provides an excellent model system for analyzing the role of growth factors in lung cancer. SCLCs secrete a wide range of peptide hormones, including some that stimulate tumor cell growth, such as gastrin-releasing peptide and insulin-like growth factor I. Many of these peptides are synthesized as prohormones that acquire biological activity only after specific post-translational modifications. Here, we review our current understanding of the biological role of neuroendocrine peptides in lung carcinogenesis and consider how a mechanistic knowledge of one particular modification, carboxy-terminal alpha-amidation, may permit identification of novel growth factors for lung cancer cells. We also describe potential applications of this knowledge as a basis for prevention-oriented approaches to the disease.

Amides↗
PubMed1991

Lung cancer: rational strategies for early detection and intervention.

The current mortality rate for lung cancer, which approaches 90% at two years, is not decreasing despite intensive clinical trials attempting to improve systemic therapy. New drug discoveries and dose intensification approaches have not resulted in more effective anti-tumor control. An alternative approach using sputum immunocytology for early lung cancer detection was recently reported. The proposed basis for this early detection reflects the underlying biology of immunodominant carbohydrate tumor-associated antigens, which are recognized as a class of oncofetal antigens. The process of bronchial epithelial carcinogenesis is associated with an evolution of carbohydrate display which reverses the sequence originally associated with fetal organ development. By elucidating this pattern of fetal carbohydrate display, a precise map of stage of bronchial carcinogenesis may emerge.

Antigens, Neoplasm↗
PubMed1989

In vivo diagnosis and therapy of human tumors with monoclonal antibodies: selection of antibodies and preliminary clinical studies in small cell carcinoma of the lung.

Initial monoclonal antibody therapy trials include an attempt to control malignant proliferation of small cell lung cancer by blocking the autocrine stimulation of gastrin releasing peptide. A critical issue is the adequacy of antibody penetration into the tumor bed to effect immunologic blockade of the mitogenic peptide. The use of an indium-111 antibody chelate which is coadministered with the first therapeutic antibody administration facilitates analysis of the pharmacokinetic dynamics for this trial. If this approach is successful with gastrin releasing peptide, other peptide hormones with autocrine effects could also be targeted. A combination of anti growth factor therapies could lead to successful therapeutic control of this lethal disease.

Antibodies, Monoclonal↗
PubMed1988

Solid-phase peptide quantitation assay using labeled monoclonal antibody and glutaraldehyde fixation.

A solid-phase radioimmunoassay utilizing iodinated peptide-specific monoclonal antibody as a detection system instead of labeled peptide has been developed. Regional specific monoclonal antibodies to either gastrin-releasing peptide or gastrin were used as models to validate the general application of our modified assay. Conditions for radioactive labeling of the monoclonal antibody were determined to minimize oxidant damage, which compromises the sensitivity of other reported peptide quantitation assays. Pretreatment of 96-well polyvinyl chloride test plates with a 5% glutaraldehyde solution resulted in consistent retention of sufficient target peptide on the solid-phase matrix to allow precise quantitation. This quantitative method is completed within 1 h of peptide solid phasing. Pretreatment of assay plates with glutaraldehyde increased binding of target peptide and maximized antibody binding by optimizing antigen presentation. The hypothesis that glutaraldehyde affects both peptide binding to the plate and orientation of the peptide was confirmed by analysis of several peptide analogs. These studies indicate that peptide binding was mediated through a free amino group leaving the carboxy-terminal portion of the target peptide accessible for antibody binding. It was observed that the length of the peptide also affects the amount of monoclonal antibody that will bind. Under the optimal conditions, results from quantitation of gastrin-releasing peptide in relevant samples agree well with those from previously reported techniques. Thus, we report here a modified microplate assay which may be generally applied for the rapid and sensitive quantitation of peptide hormones.

Amino Acid Sequence↗
PubMed1988

Growth factor effects on small cell lung cancer cells using a colorimetric assay: can a transferrin-like factor mediate autocrine growth?

A semiautomated colorimetric assay (MTT assay), based on the ability of live cells to reduce a tetrazolium-based compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), to a purplish colored formazan product that can be measured spectrophotometrically, has recently been adapted for use in drug sensitivity analysis of cultured human tumor cell lines. We report the application of this assay for the evaluation of the growth factor requirements of human small cell lung cancer (SCLC) cell lines. Specifically, the growth stimulation of each constituent of a previously reported serum-free defined medium system for SCLC including various concentrations of hydrocortisone, insulin, transferrin, 17 beta-estradiol, and selenium (HITES) was evaluated. The optimal concentrations for insulin, transferrin, and selenium derived in the previously reported experiments with direct counting of viable cells were similar to optimal concentrations determined for the growth of three SCLC cell lines (NCI-H82, NCI-N417, NCI-H526) using the MTT assay. In contrast to the previous report, the growth-stimulating effects of hydrocortisone and 17 beta-estradiol were negligible. Using the MTT we have shown that a SCLC cell line, NCI-H345 (which has been previously reported to produce a transferrin-like molecule), was growth-inhibited by an anti-transferrin receptor antibody, when grown in transferrin-free media. The conditioned media from this cell line is stimulatory to other transferrin-sensitive cell lines, suggesting the possibility of an autocrine role for this transferrin-like molecule at least in that cell line. With carefully defined conditions for a given cell line in which cell density and other parameters are within a range of constant MTT metabolism, the assay is well suited for precise analysis of growth factor effects.

Carcinoma, Small Cell↗
PubMed1988

Insulin-like growth factor-I can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro.

The effect of insulin-like growth factor I (IGF-I) on growth of small cell lung cancer (SCLC) cell lines was studied. Western blot analysis of whole cell lysates of cell lines NCI-H345 and NCI-N417 demonstrated the presence of a 16-kD band consistent with an IGF-I precursor molecule. Scatchard plot analysis of cell line NCI-H345 using 125I-labeled IGF-I demonstrated two high affinity specific binding sites (Kd 1.3 and 4.0 nM with maximal rate (Bmax) 200 and 500 fmol/mg protein, respectively). The exogenous addition of IGF-I, IGF-II, or insulin resulted in marked proliferation of human SCLC cells as evaluated using an in vitro growth assay. These peptides stimulated the growth of SCLC cell lines NCI-H82, NCI-H209, NCI-H345, and NCI-N417. The concentration of IGF-I producing maximal SCLC cell growth was 10-100-fold less than that of insulin or IGF-II, whereas the maximal growth stimulated by the optimal concentration of these peptides were similar. An MAb that specifically binds to the IGF-I receptor (but not to the insulin receptor) mediates a dose-dependent inhibition of cell growth in basal media as well as IGF-I, IGF-II, or insulin-supplemented media. The IGF-I receptor thus appears to be the common pathway for the mitogenic activity by IGF-I, IGF-II, and insulin for human SCLC cell lines. The demonstration of an IGF-I precursor molecule, specific IGF-I receptor binding, IGF-I-mediated growth stimulation, and inhibition of basal cell growth by an MAb to the IGF-I receptor suggests that an IGF-I-like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines.

Animals↗
PubMed1980

Blood group A-like activity in a long-term renal cell line.

We evaluated two renal carcinoma lines, CAKI-1 and CAKI-2, for the presence of certain cell surface antigens. CAKI-1 was from an individual with blood type O and CAKI-2 from an individual with blood type A. A modification of the standard Chromium-51 release assay was used to determine complement dependent antibody activity in the serum of test subjects against these lines. Seventy per cent of 77 sera contained complement dependent antibody activity against CAKI-2; none was reactive against CAKI-1. Eighty-three and 88 per cent of sera from subjects with blood type B and O were reactive against CAKI-2; only 25 and 26 per cent of the sera from A and AB subjects were reactive against this same line. Both cell lines were agglutinated by anti-H lectin but only CAKI-2 was agglutinated by anti-A lectin. Fourteen of 18 normal control sera and 8 of 9 sera from cancer patients were inhibited by A antigen. A Forssman antigen obtained from guinea pig kidney removed significant complement dependent antibody activity against CAKI-2 when the sera were previously absorbed with this antigen. It would thus seem that CAKI-2 has on its surface an antigen which is either a true blood group A antigen, a Forssman antigen, or a Forssman-like antigen. Of special interest is the long persistence of this antigen in culture, thus permitting further studies characterizing its nature.

ABO Blood-Group System↗
PubMed1979

Certain aspects of analysis of complement dependent antibody in breast cancer patients.

Specific anti-breast cancer complement dependent antibody (CDA) was sequentially determined in the sera of patients before and after mastectomy or during progressive recurrent breast cancer. Several observations were made. (1) There appears to be a different pattern of antigenic cross-reactivity detected by cancer patients' anti-tumor CDA than by their anti-tumor cell-mediated immunity; the former being broader than the latter. (2) Patients can be classified into three categories: those with persistent anti-tumor CDA pre- and post-mastectomy; those with detectable CDA post-mastectomy but not pre-mastectomy; and those with only occasionally detectable CDA. (3) Some sera obtained from patients with clinically evident tumor inhibited anti-tumor CDA found in the sera of other cancer patients. The significance of these results are discussed.

Adenocarcinoma↗
PubMed1976

Cell-mediated immunity in renal cell carcinoma-preliminary report.

The microcytotoxicity test was used in 8 cases post-nephrectomy for renal cell carcinoma to stage the disease clinically and to evaluate immunologically. Half of the patients had stage IV disease and half were believed to be cured clinically. Cell-mediated immunity and serum blocking factors were found in all patients with known metastases. However, cellular immunity was not found in 3 of the 4 remaining patients and serum blocking factors were also not noted in the 2 clinically cured patients who were tested. These findings are compatible with the facts that cell-mediated immunity and serum blocking factors are found when there is a grossly discernible antigenic source, that serum blocking factors are lost in patients who are clinically free of tumor and that in some patients who are clinically cured with a possible total loss of antigenic presence there is a disappearance of significant cell-mediated immunity.

Adenocarcinoma↗
PubMed1976

Antigenic cross-reactivity between adenocarcinoma of the breast and fibrocystic disease of the breast.

Peripheral lymphocytes obtained from 12 of 13 patients who had fibrocystic disease (FCD) of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. Sera from 6 women with active FCD or metastatic breast cancer could specifically block the cytotoxicity of lymphocytes from either population of patients against cancer cells. This implied extensive antigenic cross-reactivity between benign and malignant hyperplastic disease of the breast. Sera from 4 individuals clinically free of FCD or breast fibroadenoma (FAD) neutralized the blocking activity in the sera of patients with metastatic breast cancer. Patients "cured" of FCD or FAD represented a pool of potential plasma donors for immunotherapy of recurrent breast cancer.

Adenofibroma↗
PubMed1975

Antigenic cross reactivity between benign prostatic hyperplasia and adenocarcinoma of prostate.

Tissue cultures were established from biopsy specimens of adenocarcinoma of the prostate (ACP) and benign prostatic hyperplasia (BPH). Generally, peripheral blood lymphocytes from BPH and ACP patients were cytotoxic to both ACP and BPH cells, but not normal fibroblasts nor cells cultured from other types of malignant tissue. Peripheral blood lymphocytes from normal control patients or from patients with other types of cancer were not cytotoxic to ACP- or BPH-derived cells. These findings are consistent with a cross reactive autoimmune response in ACP and BPH patients, directed against a common antigen(s) present on both ACP and BPH cells.

Adenocarcinoma↗