ISSN:8756-0437    

DOI:10.1002/ssu.2980050602

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe immune system is regulated by a variety of lymphokines, monokines, and colony‐stimulating factors. Most have now been cloned and it is clear that these cytokines have a broad range of overlapping immunological, inflammatory, and physiological properties. Some of these cytokines might favorably influence the biological therapy of cancer and they have been collectively referred to by clinicians as “biological response modifiers.” This review summarizes current knowledge about the molecular biology and biological properties of most of the common cytokines and provides a brief survey of their therapeutic potential in patients with c

ISSN:8756-0437    

DOI:10.1002/ssu.2980050603

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractInterleukin‐2 (IL‐2) is a lymphokine which has a variety of in vivo immunomodulatory effects. The administration of IL‐2 can mediate enhancement of cellular immune responses, induction of lymphocyte proliferation, production of cytokines, and regression of established tumor in animal models. The availability of large quantities of recombinant IL‐2 has enabled investigators to examine its therapeutic potential in the treatment of human cancer. Several studies have documented the ability of IL‐2 administration to cause durable tumor regression in patients with advanced melanoma and renal cell cancer. Toxicity of therapy is dose related and is mediated by a vascular capillary leak syndrome, lymphocytic infiltration, and the release of cytokines secreted in response to IL‐2 administration. The side effects are completely reversible upon cessation of therapy. Future efforts are aimed at increasing the antitumor efficacy and decreasing the toxicity of IL‐2 a

ISSN:8756-0437    

DOI:10.1002/ssu.2980050604

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractInterferons play a key role in the immune system as biological response modifiers. Interferons α, β, and γ have been characterized, their nucleotide sequences defined, and the proteins produced by recombinant DNA technology. The myriad actions of interferons include enhancement of natural killer cell activity and antigen expression, induction of varied proteins, activation of macrophages, and antiviral, antiproliferative and antitumor effects. Clinical trials have demonstrated efficacy of interferons in some malignancies and ongoing studies are investigating results of combinations with other biological response modifiers and cytotoxic agen

ISSN:8756-0437    

DOI:10.1002/ssu.2980050605

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractTumor necrosis factor(TNF) is a well‐described and characterizedcytokinewhich can be elicited in the intact animal byendotoxin. This factor produces necrosis of subcutaneous tumors in the classic model: Meth A sarcoma in the Balb C mouse. It has been shown to be cytostatic or cytotoxic for a variety of human cancer cell lines, as well as to have effects against both mouse tumors and human cancers carried in the nude mouse. TNF is most likely produced by the macrophage. TNF has been cloned, and has been shown to have a molecular weight of 17,000 and to contain approximately 157 acids in its active form. The genes responsible for TNF are contained on chromosome 6 in man, which also contains genes of the major histocompatibility complex. Although there are similarities to lymphotoxin, which is produced by mitogen‐stimulated lymphocytes, and to interleukin‐1 (IL‐1), which is also produced by macrophages, TNF has distinctive differences, primarily in its antiproliferative effects. TNF is also allied with the effects of cachexia and has been shown to be similar to, if not exactly the same as,cachectin. Although it appears that effects of TNF require expression of receptors to facilitate binding to the cell, there is not a quantitative relationship between receptors and the sensitivity. TNFcytotoxiceffects appeared to be amplified by pretreatment of cells with chemotherapeutic agents such as Actinomycin D, Adriamycin, and Cytoxan as well as to have synergistic effects with gamma interferon, alpha interferon, and IL‐2. Although initial phase I and phase II studies of TNF in man have shown the expected toxicity, there have been minimalantitumor effects. It is anticipated that with more sophisticated studies, perhaps combining TNF with either biological or chemotherapeutic agents, TNF's true role in cancer therapy may we

ISSN:8756-0437    

DOI:10.1002/ssu.2980050606

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractCancer‐induced immunosuppression can be caused by a variety of effects. These include factors produced by the host in response to the presence of tumor or factors elaborated by the tumor itself. Disseminated tumor can lead to host debility with associated anergy. Some immunosuppressive effects are due to the manner in which the host processes (or fails to process) the tumor as an antigenic stimulus. Lastly, antitumor treatments can have a detrimental impact on host antitumor immunity. Recent research findings from our laboratories implicate surgical stress effects and tumor‐mediated production of growth factors such as transforming growth factor Beta (TGF‐Beta) as being important causes of host immune impairment. An accurate understanding of the mechanisms underlying host antitumor immune impairment will be critical in the successful development of immunotherapy strategies for use in the surgical oncology pa

ISSN:8756-0437    

DOI:10.1002/ssu.2980050607

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractWe have recently initiated clinical trials of active specific immunotherapy evaluating a new polyvalent melanoma cell vaccine in patients with high‐risk and/or recurrent melanoma. The vaccine has been administered alone, or in combination with low‐dose cyclophosphamide, as an immunomodulator of suppressor cells. Cyclophosphamide is effective in lowering suppressor cell activity in some patients undergoing active specific immunotherapy. This is not associated with an enhanced humoral immune response to melanoma‐associated antigens, nor is the clinical course of those patients receiving cyclophosphamide favorably influenced. We are hopeful that other immunomodulators, alone or in combination with lower does of cyclophosphamide, may be effective in some patients, particularly in those patients whose suppressor cell activity remains high. The optimization of the vaccine and the use of immunomodulators will enhance humoral and cellular immune responses to antigens in the allogenic vaccine that cross react with those present in the autologous melanoma, which should more favorably influence the prognosis of melanoma pat

ISSN:8756-0437    

DOI:10.1002/ssu.2980050608

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractTumor markers presently in use generally meet only one or two of the criteria for the ideal marker, which are: tumor specificity, correlation with tumor bulk and stage of the disease, decrease to normal after successful treatment, and rise prior to clinical manifestations of recurrence. In addition, virtually all are elevated in some benign conditions. Currently their greatest usefulness is for confirmation of clinical suspicion and for monitoring known disease. Some tumor markers which are not effective as screening tests can be used to evaluate the patient's response to therapy. The discovery of oncogenes holds great promise for a new generation of tumor markers. Major breakthroughs in the fields of molecular biology and tumor immunology seem imminent with eventual application possibly in the treatment of cancer.

ISSN:8756-0437    

DOI:10.1002/ssu.2980050609

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractSeventy‐four patients with Dukes' B2through C3colon or rectal cancer were entered into a prospectively randomized, controlled trial of active specific immunotherapy (ASI) with an autologous tumor cell‐BCG vaccine. Primary tumors were dissociated enzymatically and cryopreserved by techniques that maintain cell viability. Patients were randomized into groups treated by resection alone (control) or resection plus ASI. All patients with rectal cancer received 5,040 rads of pelvic irradiation post‐operatively. With a median follow‐up of 56 mo, there is a moderately significant difference in the distribution of time‐to‐recurrence (P= .037) and a comparably significant difference in the distributions of time‐to‐death (P= .031); both comparisons favor the ASI group. Most of the difference was due to the subgroup with colon cancer. With such small numbers of patients, we cannot conclude that ASI is of proven therapeutic benefit. The results are sufficiently encouraging that the trial is continuing and a national multi‐institutional prospectively randomized trial i

ISSN:8756-0437    

DOI:10.1002/ssu.2980050610

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY

摘要:

AbstractTumor‐associated antigens (TAA) provide appropriate targets for selective manipulation of the patient's immune response in the immunotherapy of cancer. Active specific immunotherapy utilizing antiidiotypic antibodies to anti‐TAA antibodies has been implemented in phase I clinical trials both in patients with colorectal carcinoma and in those with melanoma. The theoretical basis for immunotherapy with antiidiotypic antibodies, the results of these clinical trials, and an evaluation of appropriate parameters for future clinical trials of active specific immunotherapy with antiidiotypic antibodies in patients with solid tumors are revie

ISSN:8756-0437    

DOI:10.1002/ssu.2980050611

出版商:John Wiley&Sons, Inc.    

年代:1989

数据来源: WILEY