Cancer Immunosuppression

Cholesterol lowering Cancer, immunosuppression Parkinson s disease Urinary tract infections Peptic ulcers Cancer... 

Antibodies to sperm surface antigens are a well-documented cause of infertility. They can decrease motility, cause agglutination, and be responsible for failure of sperm to penetrate human ova. Antibodies arise from autoimmune processes that can be initiated by infection, trauma, obstruction, cryptorchidism, and cancer. Immunosuppressive therapy has shown little to no benefit. 

Fungi produce a number of inhibitors of CerS. The most studied are the fumonisins, which are produced by Fusarium verticillioides, a common contaminant of com. Fumonisins were first discovered in a search for the causal factor(s) for human esophageal cancer in the Transkei region of South Africa and two diseases encountered in agricultural animals that eat contaminated food (W.F.O. Marasas, 2001). They were subsequently found to have many pathological effects liver and kidney toxicity, renal cancer, immunosuppression (and in some cases immunostimulation), and birth defects, with the latter being seen not only in studies with experimental models (W.F.O. Marasas,... 

UV-B has various direct adverse effects on human health (skin cancer, immunosuppression, eye disorders), terrestrial plants and aquatic organisms [DNA alterations, photosynthesis inhibition, reduced growth, photoresponsiveness suppression (see Chapter 116)]. Moreover, due to the differences in UV-B sensitivity and adaptation among the various species, shifts in species composition may occur as a consequence of increased UV-B radiation, thus leading indirectly to alterations in ecosystems. ... 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Corticotropin is used for diagnostic testing of adrenocortical function. This drug may also be used for the management of acute exacerbations of multiple sclerosis, nonsuppurative thyroiditis, and hypercalcemia associated with cancer. It is also used as an anti-inflammatory and immunosuppressant drug when conventional glucocorticoid therapy lias not been effective (see Display 50-1). 

The improved short-term outcomes gained from induction therapy come with a degree of risk. By using these highly immunosuppressive agents, particularly the antilymphocyte antibodies (ALAs), muronomab-CD3 (OKT-3), and the antithymocyte antibodies, the body loses much of its innate ability to mount a cell-mediated immune response, which increases the risk of opportunistic infections and cancer.7,10... 

Prevention Minimize immunosuppressant doses avoid sun exposure (sunblock, hats, clothing) routine self-exams (skin, lymph nodes) yearly gynecologic/prostate exams AZA particularly associated with skin cancers CSA/TAC may be associated with lymphoproliferative disorders (lymphomas)... 

The most common risk factors for skin cancer development after transplantation include increased age, excessive ultraviolet (UV) light exposure, high degree of immunosuppression, Fitzpatrick skin types I, II and III, history of skin cancers, and infection by human papillomavirus.77... 

Immunosuppression—anatomic or functional asplenia, sickle cell disease, alcoholism, cirrhosis, immunoglobulin or complement deficiency cancer, HIV/AIDS, debilitated state of health... 

Measles, mumps, and rubella vaccine is a live virus vaccine that should be used with caution in immunosuppressed children, such as those with cancer receiving chemotherapy, solid organ or bone marrow transplantation, or receiving other immunosuppressive drugs, such as steroids in a dose... 

The number of immunocompromised persons is continually increasing as advances are made in medicine. The life expectancy for persons with cancer, HIV infection, and solid organ or bone marrow transplantation is increasing. Vaccination provides one tool to prevent infection in the immunocompromised host however, the individual s immuno-suppressed state will alter the response to vaccine. In general all vaccinations should be updated prior to the person becoming immunosuppressed, if possible. Once a person becomes significantly immunosuppressed, live virus vaccines should be avoided. 

Cancer occurs when the growth and function of cells are out of control in relation to normal tissue. The combination of genetic alterations and environmental toxins is the most frequent contributor to the process of carcinogenesis. In the development of skin cancer, the risk factors are categorized as environmental (solar UV radiation), genetic (family history), immunosuppression, and previous history of melanoma.10... 

There is clear evidence linking defects of the immune system to the development of NMSC. For example, it is observed that patients receiving chronic immunosuppressant therapy for organ transplantation have a 50% risk of developing SCC within 20 years of transplantation, and 30% of these cancers are highly aggressive.21 Additionally, patients with human immunodeficiency virus (HIV) infection are predisposed to melanoma.18 Data also support the idea that UV radiation... 

Acquired Immunodeficiency Syndrome (AIDS) A clinical syndrome due to infection with the RNA human immunodeficiency (retro)virus (HIV) which produces severe immunosuppression (depletion of natural killer T cells), thereby exposing the individual to a variety of opportunistic infections and cancers. 

A 45-year-old female has a bone marrow transplant for treatment of ovarian cancer Cyclosporine is given as an immunosuppressant What is the mechanism of action of cyclosporine ... 

The answer is c. (Katzung, pp 608-609, 932-9.13.) Methotrexate is classified as an anti metabolite with therapeutic uses in cancer chemotherapy and as an immunosuppressive agent indicated in the treatment of severe active classical rheumatoid arthritis. Leucovorin is related to methotrexate in that it is an antagonist of its actions. It can supply a source of reduced folate for the methylation reactions that are prevented by methotrexate. 

Mylotarg (like most other drugs) does induce some side effects, the most significant of which is immunosuppression. This is induced because certain additional (non-cancerous) white blood cell precursors also display the CD33 antigen on their surface. The immunosuppressive effect is reversed upon termination of treatment, as pluripotent haematopoietic stem cells (Chapter 10) are unaffected by the product. 

Studies using free energy calculations for the design and analysis of potential drug candidates are reviewed in section five. The chapters in this section cover drug discovery programs targeting fructose 1,6-bisphosphatase (diabetes), COX-2 (inflammation), SRC SH2 domain (osteoporosis and cancer), HIV reverse transcriptase (AIDS), HIV-1 protease (AIDS), thymidylate synthase (cancer), dihydrofolate reductase (cancer) and adenosine deaminase (immunosuppression, myocardial ischemia). 

Cyclosporine demonstrates immunosuppressive activity by inhibiting the first phase of T-cell activation. It also inhibits release of inflammatory mediators from mast cells, basophils, and polymorphonuclear cells. It is used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis. The usual dose is between 2.5 and 5 mg/kg/day given in two divided doses. Adverse effects include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias, hypertrichosis, and gingival hyperplasia. Cumulative treatment for more than 2 years may increase the risk of malignancy, including skin cancers and lymphoproliferative disorders. 

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