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P Fishman

Publications and source records attributed to P Fishman.

At least 19 recordsLinked to original sources
PubMed2004

Tolerability, pharmacokinetics and concentration-dependent hemodynamic effects of oral CF101, an A3 adenosine receptor agonist, in healthy young men.

OBJECTIVES: To assess safety, tolerability, pharmacokinetics and hemodynamic effects of oral CF 101, an A3 adenosine receptor (A3AR) agonist, in healthy men. METHODS: One single and 1 repeated dose, parallel-group, ascending dose, double-blind and placebo-controlled study in normal volunteers. In the single dose study, n = 15 subjects received 1, 5 or 10 mg oral CF101; in each group 1 subject received placebo, the remainder active CF101. In the repeat-dose study, n = 28 subjects received repeated 12-hourly oral doses of CF 101 (2, 3, 4 or 5 mg) for 7 days, in each group 2 subjects received placebo, the remainder active CF101. TEST MATERIALS: Single-dose study: CF101 in 30% Cremophor RH40. Multiple-dose sudy: CF101 in 0.5% methylcellulose suspension. Both studies: the corresponding vehicles were used as placebos. Galenicals were prepared remotely from the clinical study site to ensure double-blind nature of the study. RESULTS TOLERABILITY: Single doses up to 5 mg CF101 were safe and well-tolerated. However, the single dose of 10 mg CF101 was associated with flushing, tachycardia, nausea and vomiting, which were viewed as dose-limiting in normal volunteers. Single doses of CF101 (as well as the first of the multiple doses) were associated with increases in heart rate (8 - 24 beats/min after 5 mg and 18 - 55 beats/min after 10 mg). Multiple doses up to 4 mg 12-hourly for 7 days were safe and well-tolerated. However, the 5 mg multiple-dose group reported headache, drowsiness, hot flushes and dizziness on standing; this declined with dosing duration and was not dose-limiting in this study. Adverse events were commonest near t(max). RESULTS PHARMACOKINETICS: For oral CF101, the t(max) was always 1 - 2 h post-dose and t 1/2 about 9 h, in both the single- and multiple-dose studies. For a single 5 mg dose (mean +/- SD) C(max) = 81.6 +/- 23.6 ng/ml in the single dose study, and 63.6 +/- 22.0 ng/ml after the first of the multiple doses; AUC if was 904.0 +/- 221.9 ng.h/ml and 596.1 +/- 196.6 ng.h/ml for the 2 studies, respectively. After 7 days of multiple dosing there was little change, and AUC(0-24h) = 601.0 +/- 163.6 ng.h/ml. These pharmacokinetic parameters were linearly proportional to dose in the other treatment groups. RESULTS PHARMACODYNAMICS: Increases in heart rate were related to plasma concentration and evident only in the upper range of concentrations observed. There were no changes on ECG monitoring beyond sinus tachycardia, and, in particular, no evidence of PR prolongation in any subject (n = 43). In comparison with single doses, this response was almost absent after 7 days of dosing. Leucocytosis (increases up to about 1.5 x 10(9)/l after 5 and 10 mg) was similarly transient and reversible after multiple dosing. CONCLUSIONS: Single oral doses up to 5 mg CF101 and repeated doses up to 4 mg 12-hourly for 7 days were safe and well-tolerated. Multiple-dose CF101 pharmacokinetics were unchanged and predictable from single-dose estimates, and were linearly proportional to dose. Increases in heart rate and neutrophil count were reversible during multiple dosing and were not dose-limiting in the repeat dose study. CF101 warrants further study for its efficacy in treating human disease.

Adenosine↗
PubMed2003

Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101.

Adenosine is a purine nucleoside that acts as a regulatory molecule by binding to specific G-protein-coupled A1, A(2A), A(2B), and A3 cell surface receptors. We have recently demonstrated that adenosine inhibits tumour cell growth and concomitantly stimulates bone marrow cell proliferation via activation of the A3 adenosine receptor (A3AR). In the present study, we show that a synthetic agonist to the A3AR, CF101, at the low nanomolar concentration range, inhibits HCT-116 human colon carcinoma cell growth. This effect was reversed by the selective A3AR antagonist MRS1523, demonstrating the specificity of the response. CF101 (given orally) was efficacious in inhibiting the development of primary tumours in xenograft and syngeneic models in which mice were inoculated subcutaneously with human HCT-116 or murine CT-26 colon carcinoma cells, respectively. Moreover, CF101 suppressed (50%, P<0.01) colon cancer liver metastases in syngeneic mice inoculated to the spleen with CT-26 cells. The mechanism of action entailed upregulation of interleukin-12 production in the CF101-treated groups and potentiation of NK cell activity. In the HCT-116 xenograft model in which a combined therapy of CF101 and 5-fluorouracyl (5-FU) was examined, an additive antitumour effect was demonstrated. Moreover, CF101 prevented the 5-FU-induced myelotoxicity, resulting in normal values of white blood cell and neutrophil counts. We conclude that the A3AR agonist CF101, a small orally bioavailable molecule, exerts systemic anticancer, antimetastatic, and myeloprotective effects in colon carcinoma-bearing mice, and may serve as an adjuvant treatment to enhance the chemotherapeutic index and prevent myelotoxicity.

Adenosine↗
PubMed2001

The A3 adenosine receptor as a new target for cancer therapy and chemoprotection.

Adenosine, a purine nucleoside, acts as a regulatory molecule, by binding to specific G-protein-coupled A(1), A(2A), A(2B), and A(3) cell surface receptors. We have recently demonstrated that adenosine induces a differential effect on tumor and normal cells. While inhibiting in vitro tumor cell growth, it stimulates bone marrow cell proliferation. This dual activity was mediated through the A3 adenosine receptor. This study showed that a synthetic agonist to the A3 adenosine receptor, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-uronamide (Cl-IB-MECA), at nanomolar concentrations, inhibited tumor cell growth through a cytostatic pathway, i.e., induced an increase number of cells in the G0/G1 phase of the cell cycle and decreased the telomeric signal. Interestingly, Cl-IB-MECA stimulates murine bone marrow cell proliferation through the induction of granulocyte-colony-stimulating factor. Oral administration of Cl-IB-MECA to melanoma-bearing mice suppressed the development of melanoma lung metastases (60.8 +/- 6.5% inhibition). In combination with cyclophosphamide, a synergistic anti-tumor effect was achieved (78.5 +/- 9.1% inhibition). Furthermore, Cl-IB-MECA prevented the cyclophosphamide-induced myelotoxic effects by increasing the number of white blood cells and the percentage of neutrophils, demonstrating its efficacy as a chemoprotective agent. We conclude that A3 adenosine receptor agonist, Cl-IB-MECA, exhibits systemic anticancer and chemoprotective effects.

Adenosine↗
PubMed2001

Involvement of Wnt signaling pathway in murine medulloblastoma induced by human neurotropic JC virus.

By using the early genome of the human neurotropic polyomavirus, JCV, we have created transgenic animals that develop cerebellar primitive neuroectodermal tumors which model human medulloblastoma. Expression of T-antigen was found in some, but not all, tumor cells, and examination of the clonal cell lines derived from the tumor population showed enhanced tumorigenicity of cells expressing T-antigen in comparison to T-antigen negative cells. Considering the earlier notion on the potential involvement of beta-catenin with human medulloblastoma, we investigated various components of the Wnt signaling pathway including beta-catenin, its partner transcription factor, LEF-1, and their downstream target gene c-myc in these two cell populations. Immunohistochemical staining of the cells revealed enhanced nuclear appearance of beta-catenin in T-antigen positive cells. Results from Western blot showed higher levels of beta-catenin and LEF-1 in T-antigen positive cells in comparison to those in T-antigen negative cells. The enhanced level of LEF-1 expression correlated with the increase in DNA binding activity of this protein in nuclear extracts of T-antigen positive cells. Results from Northern and Western blot analyses revealed that the level of c-myc expression is augmented both at the RNA and protein levels in T-antigen positive cells. These observations corroborated results from transfection studies indicating the ability of JCV T-antigen to stimulate c-myc promoter activity. Further, co-transfection experiments revealed that the amount of c-myc and T-antigen protein in tumor cells may dictate the activity of JCV early promoter in these cells. These observations are interesting in light of recent discoveries on the association of JCV with human medulloblastoma and suggest that communication between JCV and the Wnt pathway may be an important event in the genesis of these tumors.

Animals↗
PubMed2001

Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor.

Adenosine is an ubiquitous nucleoside present in all body cells. It is released from metabolically active or stressed cells and subsequently acts as a regulatory molecule through binding to specific A1, A2A, A2B and A3 cell surface receptors. The synthesis of agonists and antagonists to the adenosine receptors and their cloning enabled the exploration of their physiological functions. As nearly all cells express specific adenosine receptors, adenosine serves as a physiological regulator and acts as a cardioprotector, neuroprotector, chemoprotector, and as an immunomodulator. At the cellular level, activation of the receptors by adenosine initiates signal transduction mechanisms through G-protein associated receptors. Adenosine's unique characteristic is to differentially modulate normal and transformed cell growth, depending upon its extracellular concentration, the expression of adenosine cell surface receptors, and the physiological state of the target cell. Stimulation of cell proliferation following incubation with adenosine has been demonstrated in a variety of normal cells in the range of low micromolar concentrations, including mesangial and thymocyte cells, Swiss mouse 3T3 fibroblasts, and bone marrow cells. Induction of apoptosis in tumor or normal cells was shown at higher adenosine concentrations (>100 microM) such as in leukemia HL-60, lymphoma U-937, A431 epidermoid cells, and GH3 tumor pituitary cell lines. It was further noted that the A3 adenosine receptor (A3AR) plays a key role in the inhibitory and stimulatory growth activities of adenosine. Modulation of the A3AR was found to affect cell growth either positively or negatively depending on the concentration of the agonist, similar to the effect described for adenosine. At nanomolar concentrations, the A3AR agonists possess dual activity, i.e., antiproliferative activity toward tumor cells and stimulatory effect on bone marrow cells. In vivo, these agonists exerted anti-cancer effects, and when given in combination with chemotherapy, they enhanced the chemotherapeutic index and acted as chemoprotective agents. Taken together, activation of the A3AR, by minute concentrations of its natural ligand or synthetic agonists, may serve as a new approach for cancer therapy.

Adenosine↗
PubMed2001

Health care utilization and cost in children with asthma and selected comorbidities.

Children with asthma use significantly more health services than other children, yet the majority of their health care costs are for nonasthma services. The objective of this study was to measure the impact of asthma and specific upper respiratory comorbidities on the use and cost of health care by children. A population-based historical cohort study from January 1, 1992 to December 31, 1992 was conducted. Multiple visits for otitis media, sinusitis, and allergic rhinitis were considered comorbidities. The outcome measures were nonurgent outpatient care, pharmacy fills, urgent care visits, and hospital care along with the associated total costs. Children between ages 1 and 17 years were studied (n = 71,818). Children with asthma were more likely than children without asthma to have a comorbidity (26% vs. 9%). Children with multiple visits for otitis media, sinusitis, and allergic rhinitis were 1.8, 4, and 12 times more likely, respectively, to have a diagnosis of asthma in the same year. Children with asthma had a 47% probability of being in the highest total cost quintile compared to a 29% likelihood once adjusted for comorbidities. Visits for otitis media, sinusitis, and particularly allergic rhinitis appear to be overrepresented in children with asthma and contribute to their high utilization rate. Once a high-risk cohort is identified, the needs of those children can be addressed through targeted, organized systems of care that may include guidelines or other disease management strategies.

Adolescent↗
PubMed2001

The Medicaid Rx model: pharmacy-based risk adjustment for public programs.

BACKGROUND: Risk adjustment models typically use diagnoses from claims or encounter records to assess illness severity. However, concerns about the availability and reliability of diagnostic data raise the potential for alternative methods of risk adjustment. Here, we explore the use of pharmacy data as an alternative or complement to diagnostic data in risk adjustment. OBJECTIVES: To develop and test a pharmacy-based risk adjustment model for SSI and TANF Medicaid populations. RESEARCH DESIGN: Pharmacological review combined with empirical evaluation. We developed the Medicaid Rx model, a system that classifies a subset of the National Drug Codes into categories that can be used for risk-assessment and risk-adjusted payment. SUBJECTS: Subjects consisted of 362,370 persons with disability and 1.5 million AFDC and TANF beneficiaries in California, Colorado, Georgia, and Tennessee during 1990-1999. MEASURES: We compare pharmacy and diagnostic classification for three chronic diseases. We also compare R2 statistics and use simulated health plans to evaluate the performance of alternative models. RESULTS: Pharmacy and diagnostic classification vary in their ability to identify specific chronic disease. Using simulated plans, diagnostic models are better at predicting expenditures than are pharmacy-based models for disabled Medicaid beneficiaries, although the models perform similarly for TANF Medicaid beneficiaries. Models that combine diagnostic and pharmacy data have superior overall performance. CONCLUSIONS: The performance of risk adjustment models using a combination of pharmacy and diagnostic data are superior to that of models using either data source alone, particularly among TANF beneficiaries. Concerns regarding variations in prescribing patterns and the incentives that may follow from linking payment to pharmacy use warrant further research.

Adult↗
PubMed2000

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: a role for A1 and A3 adenosine receptors.

Adenosine, a ubiquitous nucleoside, is released into the extracellular environment from metabolically active or stressed cells. It binds to cells through specific A1, A(2A), A(2B), and A3 G-protein-associated cell-surface receptors, thus acting as a signal-transduction molecule by regulating the levels of adenylyl cyclase and phospholipase C. In this study, we showed that adenosine stimulates the proliferation of murine bone marrow cells in vitro. Pharmacological studies, using antagonists to the adenosine receptors, revealed that this activity was mediated through the binding of adenosine to its A1 and A3 receptors. This result was further corroborated by showing that the two selective A1 and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) respectively, induced bone marrow cell proliferation in a manner similar to adenosine. Adenosine's interaction with its A1 and A3 receptors induced G-CSF production, which led to its stimulatory effect on bone marrow cells. These results were confirmed in vivo when we demonstrated that low-dose adenosine (0.25 mg/kg) acted as a chemoprotective agent. When administered after chemotherapy, it restored the number of leukocytes and neutrophils to normal levels, compared with the decline in these parameters after chemotherapy alone. It is suggested that low-dose adenosine, already in clinical use, may also be applied as a chemoprotective agent.

Adenosine↗
PubMed2000

At-risk drinking among patients making routine primary care visits.

BACKGROUND: Addressing non-alcoholic, at-risk patterns of alcohol consumption that are associated with increased morbidity and mortality is an important health care priority. OBJECTIVE: The objective was to describe the prevalence and characteristics of at-risk drinkers in a population-based sample of adults with routine primary care visits. METHODS: Three thousand four hundred thirty-nine patients with advance appointments in 23 primary care practices completed a health survey prior to their visit. At-risk drinking was defined as consuming an average of two or more drinks per day (chronic drinking), or two or more occasions of consuming five or more drinks in the past month (binge drinking), or, in the past month, one or more occasion of driving after consuming three or more drinks (drinking and driving). RESULTS: Prevalence was: 11% at-risk drinking; 63% light to moderate drinking; 26% abstinence. Abstainers differed from alcohol users on demographics (older, fewer Caucasian, lower income, more unemployed), other health behaviors (less exercise, lower rates of smoking, and marijuana and cocaine use), and family history of alcohol problems (lower). Abstainers also reported poorer physical and psychological health. Compared to light to moderate drinkers, at-risk drinkers were more likely to be male, unmarried, and to use other substances (tobacco, marijuana, and cocaine). Among at-risk drinkers, those with two or more risk factors were more likely male, consumed more alcohol per week, had higher AUDIT scores and were more motivated to change their drinking. Among those with only one risk factor, binge drinkers reported high rates of tobacco and marijuana use, relatively poor perceived health, and the highest proportion of negative consequences from drinking. CONCLUSIONS: At least 1 in 10 patients making routine primary care visits have drinking practices that place them at risk for negative consequences from drinking. Three drinking patterns that can be used to define at-risk drinking are relatively distinct.

Adult↗
PubMed2000

Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor.

In this study, we demonstrated several mechanisms exploring the inhibitory effect of low-dose adenosine on lymphoma cell growth. Adenosine, a purine nucleoside present in plasma and other extracellular fluids, acts as a regulatory molecule, by binding to G-protein associated cell-surface receptors, A1, A2 and A3. Recently we showed that low-dose adenosine released by muscle cells, inhibits tumour cell growth and thus attributes to the rarity of muscle metastases. In the present work, a cytostatic effect of adenosine on the proliferation of the Nb2-11C rat lymphoma cell line was demonstrated. This effect was mediated through the induction of cell cycle arrest in the G0/G1 phase and by decreasing the telomeric signal in these cells. Adenosine was found to exert its antiproliferative effect mainly through binding to its A3 receptor. The cytostatic anticancer activity, mediated through the A3 adenosine receptor, turns it into a potential target for the development of anticancer therapies.

Adenosine↗
PubMed2000

Ciprofloxacin affects pregnancy loss in CBA/JxDBA/2J mice possibly via elevation of interleukin-3 and granulocyte macrophage-colony stimulating factor production.

PROBLEM: The mechanisms mediating pregnancy loss are far from being understood, but it is believed that modulation of the maternal immune system, that is known to support pregnancy, might serve as a means for the treatment of habitual abortions. Thus, we examined the effect of the anti bacterial agent ciprofloxacin, which was shown to affect maternal immunoreactivity, on pregnancy loss in the resorption-prone CBA/JxDBA/2J mouse combination as well as associated changes in Interleukin (IL)-3 and Granulocyte macrophage-colony stimulating factor (GM-CSF) production. METHOD OF STUDY: CBA/J females mated to DBA/2J males were treated with ciprofloxacin for 5 consecutive days. On day 15 of pregnancy, the number of resorbed embryos was recorded and IL-3 mRNA expression as well as IL-3 and GM-CSF protein production by splenocytes were assayed by northern blotting and ELISA, respectively. RESULTS: Ciprofloxacin treatment resulted in a significant reduction in the resorption rate as compared to the effect of the control antibiotic ceftazidime or PBS only, while not affecting the number of implantation sites/mouse. Also, splenocytes from ciprofloxacin-treated CBA/J mice exhibited an increased level of IL-3 mRNA transcripts as well as an elevation in IL-3 and GM-CSF protein production. CONCLUSIONS: Our data demonstrate the ability of ciprofloxacin to reduce pregnancy loss in the CBA/JxDBA/2J mouse model, possibly via elevation of IL-3 and GM-CSF production.

Abortion, Veterinary↗
PubMed1999

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice.

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (< 1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16-F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread.

Administration, Oral↗
PubMed1999

Gamma-globulin inhibits tumor spread in mice.

Intravenous (i.v.) Ig is the human serum Ig fraction that is mainly composed of IgG prepared from plasma pools of over 15,000 healthy blood donors and is suitable for i.v. use. High-dose i.v. Ig is currently used to treat patients with diverse autoimmune conditions. Autoimmunity and malignancy co-exist frequently, and share etiological and pathological mechanisms. Since the two diseases are similarly treated, we studied the efficacy of i.v. Ig as a treatment for malignant conditions. The administration of i.v. Ig to mice inoculated i.v. with melanoma or sarcoma cells induced a statistically significant inhibition of metastatic lung foci and prolongation of survival time. Similar results were seen with SCID mice inoculated with SK-28 human melanoma cells. In a different model, melanoma was induced in the foot pad, followed by leg amputation, after the development of the tumor lesion. A lower number of melanoma recurrences and prolongation of survival time were demonstrated in the i.v. Ig-treated groups. In vitro studies revealed that i.v. Ig was found to stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine. Moreover, it enhanced NK cell activity, thus explaining its beneficial effect in SCID mice (which lack B and T but possess NK cells). The results indicate that i.v. Ig acts as an anti-tumor agent. Since it has only minor side effects and is used extensively for other clinical conditions, i.v. Ig may be considered as a potential therapy for the prevention of tumor spread in humans.

Animals↗
PubMed1999

Indirect costs of migraine in a managed care population.

Migraine is a highly prevalent condition that commonly affects individuals during their most productive years. The aggregate cost of providing healthcare for persons with migraine is substantial, but the economic consequences of lost and reduced productivity among this population are greater. This paper presents estimates of the annual indirect costs associated with migraine in a managed-care population. Our estimates include workplace and domestic productivity losses for persons employed outside the home as well as those persons engaged exclusively in domestic production or who are unable to work. We find that migraine is associated with annual indirect costs for men and women, respectively, of $4,548 and $4,897 in 1990 dollars, and that indirect costs increase with headache severity. Further research should continue to emphasize headache's effect on domestic production in order to avoid bias in measuring the economic effect of headache on women.

Adult↗
PubMed1999

The effect of surgically induced weight reduction on the serum levels of the cytokines: interleukin-3 and tumor necrosis factor.

BACKGROUND: Morbid obesity and malnutrition have both been demonstrated to have deleterious effects on the immune function. Cytokines are immunomodulatory peptides that have profound effects on immune function. To the authors' knowledge, the effect of surgically induced weight reduction on the cytokine levels has yet not been studied. In the present study, the authors determined the effect of surgically induced weight reduction on the levels of the cytokines interleukin-3 (IL-3) and tumor necrosis factor-alpha (TNF-alpha). METHODS: 14 patients undergoing silicone ring vertical gastroplasty were included in the study (mean BMI 48.85 kg/m2; range 38.1-52.0 kg/m2). Determination of the IL-3 and TNF-alpha levels was performed preoperatively and 14 days and 6 months postoperatively, when all patients had lost 25% to 30% of their preoperative weight. RESULTS: The IL-3 values before the procedure, and 14 days and 6 months after, were as follows: 9.69 +/- 1.82, 9.36 +/- 1.28, and 8.42 +/- 1.26 pg/mL, respectively (P < 0.05 preoperative versus 6 months postoperative level). The preoperative TNF-alpha levels showed a wide distribution. For this reason, the patients were divided into two groups: Group A with preoperative values >10 pg/mL and Group B with values <10 pg/mL. In Group A, a significant decrease from the preoperative level of 24.46 +/- 6.83 to 7.59 +/- 4.56, and 6.69 +/- 5.46 pg/mL was measured at 14 days and 6 months postoperatively, respectively (P < 0.05). In Group B, the TNF-alpha levels were not significantly changed and were 5.45 +/- 2.26, 7.59 +/- 4.56, and 8.82 < or = 6.27 pg/mL, respectively. CONCLUSION: The present study demonstrates a significant decrease in the levels of the cytokines, IL-3 and TNF-alpha. These changes can be responsible for alteration of the immune function after surgically induced weight reduction.

Case-Control Studies↗
PubMed1999

Antibodies to the cytoplasm, cell membrane and nuclear membrane of malignant neoplasms in pooled normal human polyspecific immunoglobulin G.

IVIg is a preparation of normal polyspecific IgG obtained from pooled plasma of a large number of healthy donors. IVIg treatment of patients with chronic lymphocytic leukemia induced a reduction in the total number of lymphocytes in the peripheral blood. Regression of Kaposi's sarcoma was also noted in an HIV patient treated with IVIg. The aim of this study was to determine whether F(ab')2 prepared from IVIg binds to cellular structures of different tumor tissues. Biotinylated F(ab')2 was prepared from 3 different preparations of IVIg and from affinity purified IgG from a patient with multiple myeloma. Direct immunohistochemistry using a streptavidin peroxidase staining method was performed on biopsy samples of 18 different tumor tissues. Positive staining of the cytoplasm, cell membrane and nuclear membrane of several types of malignant tumors by F(ab')2 from IVIg was immunohistochemically demonstrated. Nuclear staining of tumor cells by IVIg was rare. IVIg bound to different tumors of epithelial origin, especially colon carcinoma, breast carcinoma and squamous cell carcinoma of the lung. Malignant tumors of mesenchymal origin such as leiomyosarcoma have also demonstrated positive staining by IVIg. IVIg contains antibodies to the cytoplasm, nuclear membrane and cell membrane of different malignant tumors especially of epithelial origin. This binding might provide a basis for the assumption that IVIg treatment of cancer patients may induce antibody dependent cell mediated cytotoxicity response against tumors, and implies that it can be potentially beneficial as adjuvant treatment of malignant diseases.

Antibody Affinity↗
PubMed1998

Adenosine and other low molecular weight factors released by muscle cells inhibit tumor cell growth.

In this study, we investigated the basis of the resistance of muscles to tumor metastases. We found that a low molecular weight fraction (Mr <3000) of skeletal muscle cell-conditioned medium (MCM) markedly inhibits the proliferation of carcinoma, sarcoma, or melanoma cell lines in vitro. The MCM exerts a cytostatic effect on tumor cell growth and arrests the cells in G0/G1 of the cell cycle. However, normal cell proliferation of cells such as bone marrow cells or fibroblasts was found to be refractory to the influence of the MCM. A reduction in melanoma growth was observed in mice treated with the MCM. Adenosine was identified as one of the active components in the MCM by using high-performance liquid chromatography separations, mass spectra, and nuclear magnetic resonance analyses. At a concentration of 4 microM, equal to that found in the MCM, adenosine inhibits the proliferation of tumor cell lines (Nb2 lymphoma, K-562 leukemia, and LNCaP prostate carcinoma cells) while stimulating the proliferation of normal murine bone marrow cells. By similar methods, additional inhibitory components were detected in the MCM in a molecular mass range of 600-800 Da. The ability of adenosine and other low molecular weight components to specifically inhibit tumor cell growth in vitro and in vivo may account for the resistance of muscle to tumor metastases.

Adenosine↗