摘要:

Summary:Oral and subcutaneous administration of specific preparations of bovine tracheal cartilage rings (Catrix), a nontoxic agent, has resulted in a high response rate in 31 cases of a variety of clinical malignancies (response rate 90%, 61% complete). The demonstrated responders include present therapeutic disasters such as glioblastoma multiforme and cancers of the pancreas and lung. Other types which were treated with success included cancers of the ovary, rectum, prostate, cervix, thyroid, and an inoperable squamous cancer of the nose. These responses were observed when full dose therapy was given over prolonged courses of treatment (years). This wide range of Catrix efficacy now invites investigation by others to confirm the effectiveness of the material and to isolate the molecular entities responsible for these unexpectedly favorable results.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Catrix‐S is an acidic mucopolysaccharide complex derived from bovine tracheal cartilage. This material was administered by weekly subcutaneous injection (5.0‐7.5 g/week) to nine patients with progressive metastatic malignancy. One complete response was seen in a patient with metastatic renal cell carcinoma to the lungs. Eight patients had progression of their disease. No undue toxicity and no consistent immunologic alteration was noted.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Catrix is an acidic mucopolysaccharide complex derived from bovine tracheal cartilage. The antitumor efficacy of Catrix has been evaluated in the human tumor stem cell assay system using three human tumor cell lines and fresh biopsy specimens from 22 patients with malignant tumors. In vitro efficacy has been demonstrated with high dose continuous exposure Catrix, particularly against the 8226 human myeloma cell line as well as ovarian, pancreatic, colon, testicular, and sarcoma biopsy specimens. The level of sensitivity was at ≤30% survival of colony growth in vitro. Since the in vitro concentrations may be achievable in vivo, the results justify more detailed in vitro evaluation as well as potential clinical trials.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Intravenous infusions of 250,000 U of lymphocyte‐derived or recombinant DNA‐derived interleukin‐2 (IL‐2) were administered to patients with the acquired immunodeficiency syndrome, and sera were obtained for pharmacokinetic studies. A methodology was developed for the determination of serum levels of interleukin‐2, which resulted in a coefficient of variation of less than 8% and a sensitivity 32‐fold greater than that of the traditional methodology using probit analysis of half‐maximal stimulation. In addition to the previously described rapid clearance of IL‐2, a later phase of interleukin‐2 clearance with a half‐life greater than 90 min was observed; bioactive interleukin‐2 remained in the circulation for several hours after infusion.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Twenty children with hematologic malignancies were treated with bone marrow transplantation using histoincompatible donor marrow depleted of T lymphocytes. CT‐2 and complement were used to deplete the T lymphocytes. Engraftment was not a major problem in those receiving increased pre‐ and posttransplant immunosuppression. Five of the 20 children are currently alive and disease‐free. Complications in the other children included engraftment problems, cyclosporin toxicity, infections, and bleeding. However, for most children, durable engraftment was seen. Thus, the nonavailability of histocompatible donors is no longer a contraindication to allogeneic bone marrow transplantation for those at high risk of relapse.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Historically, it has been assumed that double‐stranded (ds) RNAs function at a cellular level exclusively via an interferon (IFN) induction mechanism. However, current studies conducted both in the laboratory and at the clinical level reveal that this assumption is incorrect and, indeed, underestimates the intrinsic antitumor activity of certain dsRNAs. A specific dsRNA (Ampligen) shows strong antiproliferative activity against human carcinoid tumor cells in a clonogenic assay when natural &agr;‐ and &bgr;‐IFNs were inactive. Similarly, in vivo studies in which human renal cancer cells were transplanted into athymic mice demonstrate a strong antitumor effect of Ampligen whereas such tumors are largely unaffected by &agr;‐IFN treatment. In a comparative study including many fresh human turnors of various histological types (breast, ovarian, melanoma, renal, and carcinoid) numerous examples were uncovered of Ampligen sensitivity (antiproliferative effect) in the face of relative or complete insensitivity to IFNs. Synergistic effects of Ampligen plus IFN overcame the resistance of some human tumor cells to either biological modifier given alone. It can also be demonstrated that the antitumor action of Ampligen on certain human lung tumor cells is not shared by polyinosinic polycytidylic acid, thus indicating that different dsRNAs may themselves exhibit dissimilar effects on various human tumors.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Polyinosinic‐polycytidylic acid stabilized with poly‐L‐lysine in carboxymethylcellulose [poly(I,C)‐LC] significantly augmented natural killer (NK) cell activity in several tissues. Macrophage (M&phis;) tumoricidal activity was also markedly increased. Both effector cells were active for 9 days. Poly(I,C)‐LC also increased effector cell response in vitro. Injections of poly(I,C)‐LC resulted in elevated effector cell responses in four of five routes tested. Treatment with poly(I,C)‐LC led to an earlier reconstitution of bone marrow cells, NK cell activity, and M&phis; effector cell activity in mice pretreated with cyclophosphamide (Cytoxan). Combined treatment of MBL‐2 tumor cells with cytoreductive chemo‐therapy and poly(I,C)‐LC resulted in an enhanced therapeutic response.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Polyriboinosinic‐polycytidylic acid with poly‐L‐lysine stabilized with carboxymethylcellulose [poly(I,C)‐LC] augmented, in a dose‐ and time‐dependent manner, secretion of colony‐stimulating factor (CSF) by peritoneal macrophages (M&phis;) and bone marrow cells (BMC). Optimal effects were found after 2 days of in vitro culture of the cells with 50 &mgr;g/ml of poly(I,C)‐LC or 14 h to 3 days after a single intraperitoneal injection of 1‐2 mg/kg of poly(I,C)‐LC into normal mice. The increase in CSF secretion by M&phis; and BMC was paralleled in vivo by an increase in serum CSF levels, followed by a rise in committed granulocyte and M&phis; progenitor cells (GM‐CFU‐C), nucleated BMC, and blood leukocytes of myelomonocytic origin. Poly(I,C)‐LC at doses >4 mg/kg, however, were strongly myelosuppressive. In vitro treatment of undifferentiated myelomonocytic leukemia cells from the WEHI‐3B cell line with 10‐1,000 &mgr;g/ml of poly(I,C)‐LC resulted in a significant increase in CSF secretion by the leukemic cells and a concomitant inhibition of their proliferation. Incubation of cells from the WEHI‐3B D+subline, which differentiate in response to GM‐CSF or G‐CSF, with 50‐100 &mgr;g/ml poly(I,C)‐LC in agar cultures induced in ∽45% of the leukemic colonies a differentiation into granulocytes and/or M&phis;. Poly(I,C)‐LC, however, had no effect on differentiation of cells from the CSF unresponsive WEHI‐3B D+subline. The CSF‐inducing biological response modifier poly(I,C)‐LC thus has the potential to stimulate growth and differentiation of normal, as well as differentiation of malignant myelopoietic progenitor cells.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:Mouse interferon, or human hybrid recombinant interferon &agr;A/D, administered during the 2 day period following the administration of a toxic dose of 5‐fluorouracil (FUra), yielded significant protection from body weight loss, leukopenia, and mortality in Balb/c × DBA/8 F1 mice. Protection against FUratoxicity also was observed when the interferon inducer polyinosinic‐polycytidylic acid [poly(I,C)] was administered with FUra. Since it is known that nonproliferating cells exhibit diminished sensitivity to FUra as compared with proliferating cells, it appears likely that the decreased toxicity seen in these experiments can be ascribed to the antiproliferative action of interferon on normal tissues in the mouse which are sensitive to the action of FUra. When poly(I,C) and FUra were coadministered to mice bearing colon tumor 26, the tolerated dose of FUra was increased significantly, and this resulted in significantly increased antitumor activity. These results indicate that differential cytokinetic modulation with interferon, or possibly with other known antiproliferative agents, may provide a new approach for improving clinical results in cancer therapy with available drugs.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Summary:We have performed Phase I trials of two synthetic double‐stranded polyribonucleotide complexes—poly(I,C)‐LC, a complex of polyinosinic‐polycytidylic acid with poly‐L‐lysine and carboxymethylcellulose, and poly(I,C)‐L, which lacks carboxymethylcellulose—in patients with advanced cancer. With poly(I,C)‐LC, several treatment schedules were investigated in an attempt to decrease toxicity and maximize interferon (IFN) induction. The best tolerated was an alternate‐day schedule, with gradual dose escalation. Daily short infusions and continuous (24‐h) infusions were tolerated less well. Maximum tolerated doses varied over a several hundredfold dose range. Toxicity consisted of fever, rigors, hypotension, and blood count depression. Two patients treated with poly(I,C)‐L developed systemic allergic reactions, and antibodies to poly(I,C)‐L and its components were detected in the serum of some patients treated with both compounds. IFN‐α was induced in most patients at serum levels similar to those achieved after intramuscular administration of human IFN‐α. Of 32 patients, one with renal cell carcinoma showed partial tumor regression. Poly(I,C) complexes are effective IFN inducers in humans, but their toxicity limits their use in cancer patients.

ISSN:0732-6580    

出版商:OVID    

年代:1985

数据来源: OVID