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Soft Tissue Sarcomas
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Thomas F. DeLaney, David C. Harmon, Karol Sikora, Francis J. Hornicek
Dose intensity may be important. Very high-dose ifosfamide had been used with high response rates despite some toxicity. Higher-dose therapy with standard agents may require special supportive care such as bone marrow transplantation, but may offer a chance for higher CR rates and longer response duration. Considerable interest has been focused on maintaining dose intensity of chemotherapy using colony-stimulating factors to alleviate myelosuppression. Granulocyte–macrophage colony-stimulating factor (GM-CSF) or G-CSF has been used with a variety of regimens to help maintain dose intensification. In a few studies this has resulted in improved response rates. Even higher-dose chemotherapy, as used at M.D. Anderson, seems to result in higher response rates (59%–69%). Attempts to intensify treatment by increasing the dose of doxorubicin in combination with ifosfamide, although promising in phase II studies, were not confirmed in a subsequent randomized trial compared with the standard doses.48 High-dose therapy with growth factor support has been evaluated in several investigational studies but the data to date demonstrate increased toxicity without clear evidence of therapeutic gain, so this is still considered investigational treatment.
Immunomodulation in Gene Therapeutics
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Andreas Block, Susan S. Rich, Shu-Hsia Chen, Savio L. C. Woo
Granulocyte macrophage colony stimulating factor (GM-CSF) has a broad range of functions as a growth and survival factor as well as an enhancer of the function of mature blood cells [120–122]. Most of its properties affect progenitors of granulocytes, monocytes, and eosinophils as a growth factor, extending their lifespan and augmenting their functional capability. Neutrophils and macrophages show enhanced antibody-dependent cytotoxicity. In addition, GM-CSF is an important immunopotentiating factor, expanding potent antigen presenting cells [123–125] as well as augmenting antigen presenting abilities of mature macrophages [126,127], and therefore dramatically enhancing the host response to antigen.
Lung cancer inhalation therapeutics
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Tumor-associated macrophages have a significant role in controlling the tumor microenvironment, and inhalation of granulocyte macrophage colony stimulating factor (GM-CSF) could activate these cells. In humans, inhaled GM-CSF (500 μg/day in 2 divided doses) has modest effects in patients with pulmonary metastasis (113). In patients with metastatic melanoma, aerosol delivery of GM-CSF may induce melanoma specific immunity, similarly to an in vivo dendritic cell vaccination (114). In experimental and human studies, destruction of tumor cells by activated macrophages could prolong survival.
The Goiânia incident, the semiotics of danger, and the next 10,000 years
Published in Clinical Toxicology, 2023
Joseph Clemons, Adam Blumenberg
Observations from serial bone marrow aspirates and biopsies corresponded with changes in granulocyte concentrations. The granulocyte recovery kinetics demonstrated a marked difference between treated and untreated individuals. Moreover, the application of granulocyte-macrophage colony-stimulating factor did not appear to influence the recovery of red blood cells or platelets. Four out of eight patients treated with granulocyte-macrophage colony-stimulating factor survived, with the fatalities being patients colonized with gram-negative bacteria prior to the initiation of granulocyte-macrophage colony-stimulating factor treatment. The side effects of granulocyte-macrophage colony-stimulating factor treatment were generally mild. Some instances of respiratory failure and/or pulmonary edema were reported during therapy, predominantly in patients with bacterial sepsis. Although these episodes were primarily attributed to infection, an effect of granulocyte-macrophage colony-stimulating factor could not be definitively excluded. Both patients who exhibited spontaneous hematological recovery survived, with one requiring forearm amputation due to severe radiation burns [15].
Combining the past and present to advance immuno-radiotherapy of cancer
Published in International Reviews of Immunology, 2023
Ioannis M. Koukourakis, Michael I. Koukourakis
The ‘cytokine era’ started in 1986 with the approval of IFNα for the treatment of hairy cell leukemia [101]. IFNα was subsequently approved for the treatment of malignant melanoma, follicular lymphoma, and AIDs-related Kaposi sarcoma. In 1992, IL-2, another important cytokine, was approved for the treatment of renal cell cancer [35]. In the context of granulocyte stimulation as support to chemotherapy therapy, GM-CSF (granulocyte-macrophage colony stimulating factor) became available in clinical practice [102]. Further to its efficacy as a neutrophil stimulator, GM-CSF has important immunostimulatory effects that did not focus proper attention at that era [103]. In the modern era of immunotherapy, all these cytokines are under reevaluation, as the interferon response pathways are critical for dendritic cell and cytotoxic lymphocyte activation and regulatory T-cell suppression [104].
Synergistic Therapeutic Effects of Probiotic Lactobacillus casei TD-2 Consumption on GM-CSF-Induced Immune Responses in a Murine Model of Cervical Cancer
Published in Nutrition and Cancer, 2022
Elahe Abdolalipour, Mehran Mahooti, Ali Gorji, Amir Ghaemi
There has been a great interest in the activation of immune response due to the side effects and drawbacks associated with conventional treatments and there have been many efforts directed toward the development of new immunotherapy agents (8). Cancer immunotherapy involves the use of natural or synthetic therapeutic components that empower the immune system to recognize, attack and destroy cancer cells (10). The application of immunostimulatory cytokines represents a promising strategy in cancer immunotherapy. Among immunostimulatory cytokines, Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to augment the immune response both in animal models and clinical trials. Additionally, the critical role of GM-CSF in modulating the immune response and maintaining immunological tolerance has been established (11).