Immunotherapy and chemotherapy

Treatment of cancer includes surgical intervention, radiation, immunotherapy, and chemotherapy using neoplastic drugs. Chemotherapy is currently used in addition to surgical intervention in order to remove possible metastatic cells that still remain. Moreover, some types of tumors are currently treated first with chemotherapeutic agents. 

Cytokine-based immunotherapy and chemotherapy have been much improved. Even so, the prognosis of advanced tumors is still poor. Tumor-directed Abs, particularly bispecific (Bs) Abs (containing one tumor-directed specificity and one directed toward a cytotoxic trigger molecule on leukocytes). 

It seemed logical to him that, because the factories were turning out simple substances that differentiated between various tissues in Man, it should be possible to synthesize other small molecules which would differentiate between Man and his parasites. The emphasis on low molecular weight illustrates the contrast which Ehrlich made between immunotherapy and chemotherapy. He realized that immunotherapy was a matter of strenghtening the defence forces of the body, but he conceived of chemotherapy as a direct attack upon the parasite. The problem, as he saw it, was to find chemicals with veiy much stronger affinities for the parasites than for the tissues of the host. 

W. Regelson, Advances in intraperitoneal (intercavitary) administration of synthetic polymers for immunotherapy and chemotherapy, J. Bioact. Comp. Polymers, 1,84-106,1986. 

Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that postsurgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. 

Diagnosis Be suspicious if an aerosol attack occurs in the form of yellow rain with droplets of yellow fluid contaminating clothing and the environment. Confirmation requires testing of blood, tissue and environmental samples. As for treatment, there is no specific antidote however, super-activated charcoal should be given orally if the toxin is swallowed. The only defense is to wear a protective mask and clothing during an attack. No specific immunotherapy or chemotherapy is available for use in the field. 

Transitional cell carcinoma of the bladder is diagnosed in approx 50,000 individuals in the United States each year, and accounts for 10,000 deaths annually. A majority of patients will present with nonmuscle-invasive disease, be treated adequately with transurethral resection (TURBT) with or without intravesical chemotherapy or immunotherapy, and will have only a 10-15% risk (higher for higher grades) of developing muscle-invasive disease. In contradistinction, the natural history of muscle-invasive disease is much more aggressive, with a 5-yr survival of only 50%. 

Radiation therapy constitutes, together with surgery and chemotherapy, one of the three traditional and recognized methods of cancer treatment. In addition, novel approaches, such as immunotherapy and gene therapy, are developing and appear to be promising. 

Treatment modalities for colorectal cancer include surgery, XRT, chemotherapy, immunotherapy, and new targeted molecular therapies. Surgery is the most important and deflnitive procedure associated with cure radiation therapy can be used to improve curability following surgical resection and to reduce symptoms and complications... 

The pursuit of chemical agents that can more effectively treat cancer has led to many decades of research by a multitude of chemists, biochemists, microbiologists, biologists, and research physicians. Thousands of chemicals have been synthesized and tested in tissue cultures and animal models. Only a modest number have proved to be useful in treating humans, but they have become the mainstay of the chemotherapeutic attack on cancer. In combination with early detection, surgery, radiation, and newly developing immunotherapies and targeted therapies, the judicious use of chemotherapy can kill tumors and fimit their recurrence. 

Tumor Acidosis and Treatment Resistance 282 Effects of Tumor Acidosis on Ionizing Radiation 282 pH and Chemotherapy 284 pH and Immunotherapy 284... 

Tredan et al. 2007), tumor hypoxia plays a pivotal role in acquired treatment resistance, since O2 depletion in soHd tumors is classically associated with resistance to radiotherapy, but has also been shown to diminish the efhcacy of certain forms of chemotherapy, of photodynamic therapy, immunotherapy and hormonal therapy (for reviews since 2000, see Chaplin et al. 2000 Vau-PEL etal. 2001a,b, 2002, 2004 Vaupel and Mayer 2005 Shannon et al. 2003 Vaupel 2004b Weinmann et al. 2004 Brown 2002, 2007 Tannock et al. 2005 Kurebayashi 2005 Hall and Giaccia 2006 Liao etal. 2007 Vaupel and Hockel 2008 Bristow and Hill 2008). 

In addition, a stimulation of hemopoietic systems and bone marrow cell proliferation was observed. When P. granulosum was administered to mice several days before the irradiation with a lethal dose of X-rays (850 rad), the life span of the animals was significantly prolonged. For the treatment of patients it was suggested to combine immunotherapy with intensive radio-and chemotherapy. Roszkowski et al., (1982) concluded that P. granulosum KP-45, having a relatively low toxicity, could be used as a common adjuvant in anticancer therapy. 

NO donors have the potential to be tumor cytotoxic agents. Thus, nitric oxide donors have the dual functions of both sensitizing tumor cells to chemotherapy and immunotherapy and are also involved in the regulation and inhibition of metastasis. NO donors constitute a promising new class of mmor cytotoxic agents. In this section, we introduce some examples of the cytotoxic characteristic that have been reported. 

Although surgery, chemotherapy, immunotherapy, and radiation therapies effectively control many cancers at the primary site, the development of metastatic disease signals a poor prognosis with increased morbidity and mortality. Relatively... 

Metastatic renal cell carcinoma has a poor prognosis and resists conventional chemotherapy. Immunotherapy with IL-2 and/or IFN-a is currently regarded as the most effective therapy with, however, modest response rates of 15-20%. Similar results are also observed in patients with metastatic melanoma and the response to IFN-a and IL-2 correlates with the occurrence of tumor-infiltrating CD4+ T-lymphocytes identified in aspirates from melanoma metastases. Determination of these cells therefore seems to be a method to predict responders prior to the initiation of cytokine therapy. 

The modality of treatment for skin cancer depends on the size, location, and stage of the tumor the age of the patient and the type of skin cancer. Treatment options for skin cancer include surgery, radiation, chemotherapy, and immunotherapy. 

Clinical trials combining chemotherapy and immunotherapy are based on the observations of independent clinical activity of each of these treatment modalities in treating metastatic MM. This combination is known as biochemotherapy. Only one phase III clinical trial showed significant improvement in response rate, time to progression, and median survival favoring the biochemotherapy arm versus the combination-chemotherapy arm.59 Currently, the use of biochemotherapy is not justified outside a clinical trial in patients with stage IV MM.53,58,60... 

Unfortunately, the reality of the situation is not so simple. However large the arsenal of weapons that clinicians may have at their disposal, there are more than 40 kinds of tumors that cannot be cured at all nowadays by any medical approach. Thus, for such tumors, diagnosis means unstoppable slides to death. The situation is scarcely better for about 40 other tumors, mainly when they are so spread out over the whole body that surgery and radiotherapy cannot be used, so that chemotherapy and immunotherapy have to be employed. 

Sword (surgery), artillery (radiotherapy), asphyxiating gases (chemotherapy) and jiu-jitsu or aiki-do (immunotherapy) are the four weapons against cancers. They must be used in concert in any clinical treatment of localized tumors which can be concomitantly excised, irradiated and/or size-reduced by a drug. 

However, as we mentioned above, chemotherapy and immunotherapy are still the only weapons applicable either when solid tumors are delocalized over a large area of the body or when the tumors are liquid (ascites tumors like leukemias). 

Grohn P, Heinonen E, Klefstrom P, Tarkkanen J. Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage IB breast cancer. Cancer 1984 54 670-674. 

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