Kaposi Sarcomas

AIDS (acquired immunodeficiency syndrome) is the final stage of disease caused by infection with HIV. In this stage, the vims infection has severely affected the immune system, causing a depletion of CD4+ T-helper cells. AIDS is characterized by the manifestation of typical diseases caused by opportunistic infections (Pneumocystis carinii pneumonia, CMV retinitis, candidiasis of the esophagus, cerebral toxoplasmosis), neurological manifestations, cachexia, or certain tumors (Kaposi sarcoma of the skin, B-cell lymphoma). 

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

Baiillari G, Gendelman R, Gallo RC, Ensoli B (1993) The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the ROD amino acid sequence. Proc Natl Acad Sci USA 90(17) 7941-7945... 

Russo JJ, Bohenzky RA, Chien MC et al. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci USA 1996 93[25] 14862—14867. 

As an example, we present in Exhibit 10.8 the synthesis of paditaxel (Taxol, Bristol-Myers Squibb), an important anticancer drug for breast and ovarian cancer and Kaposi sarcoma. It illustrates the complexity in the synthesis of drug molecules. 

WARNING Chemo agent handle w/ caution Uses Hodgkin Dz NHLs, mycosis fungoides, CAs (testis, renal cell, breast, NSCLC), AIDS-related Kaposi sarcoma, choriocarcinoma, histiocytosis Action X Microtubule assembly Dose 0.1-0.5 mg/kg/wk (4-20 mg/m ) X in hepatic failure Caution [D, ] Contra IT use Disp Inj SE i BM (esp leukopenia), NA, constipation, neurotox, alopecia, rash, myalgia, tumor pain Interactions T Effects W/ erythromycin, itraconazole X effects W/ glutamic acid, tryptophan X effects OF phenytoin EMS T Risk of... 

Produced by recombinant DNA technology, IFN-a-2a is used for the treatment of chronic myeloid leukemia, Kaposi sarcoma, lymphoma, hairy cell leukemia, hepatitis B and C and cancer of the skin and kidney. It can only be administered by injection or into the bloodstream, and the most common method is subcutaneous injection. This cytokine can be injected every day however, commonly it is... 

Sattler F, Levine AM. Clinical effect of glucocorticoids on Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). Ann Intern Med... 

Tebbe B, Mayer-da-Silva A, Garbe C, von Keyserlingk HJ, Orfanos CE. Genetically determined coincidence of Kaposi sarcoma and psoriasis in an HIV-negative patient after prednisolone treatment. Spontaneous regression 8 months after discontinuing therapy. Int J Dermatol 1991 30(2) 114—20. 

Alfa-2a (Roferon-A] Hairy cell leukemia Kaposi sarcoma (AIDS related]... 

AIDS is a life-threatening disorder because of the susceptibility of the immunocompromised patient to severe infections and certain forms of cancer.65 73 76 101.113 [n particular, patients with AIDS often suffer from severe viral infections (CMV, various herpesvirus infections), bacterial infections (Mycobacterium tuberculosis), fungal infections (Pneumocystis jiroveri), and infections caused by various other microbes and parasites. Patients with AIDS also develop relatively unusual neoplastic diseases, such as Kaposi sarcoma. 

Paclitaxel Taxol Carcinoma of the breast, ovaries Kaposi sarcoma nonsmall cell lung cancer Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia] hypersensitivity reaction (skin rash/itching, shortness of breath] joint/muscle pain peripheral neuropathies Gl distress (nausea, vomiting, diarrhea]... 

Vinblastine Velban, Velsar Carcinoma of breast, testes, other tissues Hodgkin disease non-Hodgkin lymphomas Kaposi sarcoma Blood disorders (primarily leukopenia] Gl distress (nausea, vomiting] hair loss central and peripheral neuropathies local irritation at injection site... 

Drug(s) Biologic response modifiers Interferons Interferon alfa-2a [Roferon-A] Interferon alfa-2b [Intron-A] Primary Antineoplastic Indication(s) Hairy-cell leukemia Kaposi sarcoma chronic myelocytic leukemia renal and bladder cancers Common Adverse Effects Flulike syndrome [mild fever, chills, malaise]... 

Biomarkers can also be used to identify factors that increase the likelihood that an individual will develop disease. This is an important area of research in molecular epidemiology as it becomes more evident that not all risk factors will contribute to disease equally across the human population. Therefore, in order to determine whether an environmental agent is related to disease, those factors that are also required for disease development need to be taken into account. Otherwise, many disease risk factors may go undetected. Examples of susceptibility factors that can be ascertained using biomarkers are some viral infections, which may predispose to specific diseases (for example, HIV infection and Kaposi sarcoma) or HBV infection and liver cancer. Biomarkers can also be used to measure dietary factors that can contribute to disease. The most common susceptibility factor studied using a molecular epidemiological approach are hereditary factors, which are discussed in the following section. 

Presant, C. A., Blayney, D., Proffitt, R. D., Turner, A. F., Williams, L. E., Nadel, H. I., Kennedy, R, Wiseman, C., Gala, K., and Crossley, R. J. (1990), Preliminary report Imaging of Kaposi sarcoma and lymphoma in AIDS with indium-ill-labelled liposomes, Lancet, 335,1307-1309. 

Albini, A., Fontanini, G., Masiello, L., Tacchetti, C., Bigini, D., Luzzi, P., Noonan, D. M. and Stetler-Stevenson, W, G. (1994). Angiogenic potential in vivo by Kaposi sarcoma cell-free supernatants and HIVl-tat product inhibition of KS-like lesions by TlMP-2. AIDS 8,1237-1244. 

Krown SE, Gold JW, Niedzwiecki D, Bundow D, Flomenberg N, Gansbacher B, Brew BJ. Interferon-alpha with zidovudine safety, tolerance, and clinical and virolo-gic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1990 112(11) 812-21. 

Viral, parasitic, and bacterial infections have been linked to cancer (Table 9). DNA viruses such as Epstein-Barr, hepatitis B, hepatitis C, papillomaviruses, and Kaposi sarcoma herpes virus and RNA viruses such as human T-cell leukemia virus type I and human immunodeficiency virus have been implicated in causing cancer in humans and are listed as known-to-cause-cancer in humans by the International Agency for Research on Cancer (lARC). In man, the liver fluke, Opisthorchis viverrini, is associated with the development of cholangiocarcinomas of the liver and the blood fluke. Schistosoma haematobium, with carcinoma of the urinary bladder. There is evidence that chronic Helicobacter pylori infection of the stomach in man is not only related to... 

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