Wilms’ tumors

Wilms tumor Wilson model Wilson plots Wilson s disease Wilson s equation... 

Dactinomycin is useful against several tumors especially Wilms tumor of the kidney and rhabdomyosarcoma. Wilms tumor normally requires a combination of surgery, x-ray irradiation, and dactinomycin plus vincristine [57-22-7] or other antitumor agents. Resistance of the multidmg... 

Neoplasm (e.g., renal cell carcinoma and Wilms tumor)... 

Vincristine (VCR, Oncovin) ALL HD NHL multiple myeloma breast cancer SCLC, KS brain tumors soft tissue sarcomas osteosarcomas neuroblastoma Wilms tumor... 

Wilms tumor A kidney cancer that primarily affects children. 

WT1 Wilms tumor Loss of +KS form Frasier syndrome Klamt et al. (1998)... 

Kano, Y., and J. B. Little. 1989. Efficient immortalization by SV40 T DNA of skin fibroblasts from patients with Wilms tumor associated with chromosome lip deletion. Mol Carcinog 2(6) 314—21. 

Other important diseases caused by deletions include Williams syndrome, Wolf-Hirschhorn syndrome, DiCeorge syndrome, Wilms tumor, and the Prader-Willi and Angelman syndromes (see Chapter )) ... 

Y. Oka, O.A. Eiisseeva, A. Tsuboi, H. Ogawa, H. Tamaki, H. Li, Y. OJi, E.H. Kim, T. Soma, M. Asada, K. Ueda, E. Maruya, H. Saji, T. Kishimoto, K. Udaka, and H. Sugiyama, Human cytotoxic T iymphocyte responses specific for peptides of the wild-type Wilms tumor gene (WTl) product, Iininunogenetics 51, 99-107 (2000). 

Inaeased risk of various cancers (e.g., lymphatics, blood, stomach, prostate, testes, brain, and soft tissues) was reported upon exposure to pesticides (Zahm and Blair 1993 Hayes et al. 1995 Zahm et al. 1997). Children s cancer, including brain tumors, leukemia, non-Hodgkin s lymphoma, sarcoma, and Wilms tumor due to direct or parental exposure to pesticides also has been determined (Fear et al. 1998 Kristensen et al. 1996 Pogoda and Preston-Martin 1997 Sharpe et al. 1995 Buckley et al. 1994). Often, the risk of cancer due to exposure to pesticides has been higher in children than in adults (Zahm and Ward 1998). Moreover, birth defects, including limb-reduction defects, have been linked to exposures to pesticides (Restrepo et al. 1990 Schwartz and LoGerfo 1998 Lin et al. 1994), as has a higher-than-normal risk of stillborn births (Pastore et al. 1997). 

In K562 cells TPA activated the MDRl promoter and led to increased MDRl mRNA levels. This activation was mediated by the zinc finger transcription factor EGRl. This activation by TPA was inhibited by the Wilms Tumor suppressor WTl (McCoy et al., 1995 McCoy et al., 1999). Controversial response to TPA may depend on the presence or absence of EGRl or WTl in the cell lines investigated. 

This pediatric cancer stands as an example of how cooperative group studies (NWTS and SIOP) have been able to integrate both chemotherapy and radiation into standard therapy while minimizing side-effects and dramatically improving cure rates as seen in the improvement of the 5-yr relative survival rates from 74% in 1974-1976 to 93% in 1989-1996 (60). The fifth NWTS trial began in 1995 and is expected to continue until 2003 (see Table 5) (60). This study will search for biological prognostic factors and examine the rates of cancer and birth defects in children born to survivors of Wilms tumor. 

Table 5 Guidelines for Therapy of Wilms Tumor from NWTS-V ...

Neville HL, Ritchey ML. Wilms tumor. Overview of National Wilms Tumor Study Group results. Urol Clin North Am 2000 27(3) 435 142. 

Doxorubicin (Adriamycin, Rubex) [Antineoplastic/ Anthrocycline Antibiotic] Uses Acute leukemias Hodgkin Dz NHLs soft tissue, osteo Ewing sarcoma Wilms tumor neuroblastoma bladder, breast, ovarian, gastric, thyroid, lung CA Action Intercalates DNA X DNA topoisomerases I II Dose 60-75 mg/m q3wk X w/ hqjatic impair IV use only X... 

Its mechanism of action is based on intercalation in the minor groove of double stranded DNA, interference with RNA polymerase and with topoiso-merase II. Its primary indications are rhabdomyosarcoma and Wilms tumor in children. In combination with methotrexate, it is used in the treatment of choriocarcinoma. 

Childhood Acute lymphocytic leukemia Burkitt s sarcoma Ewing s sarcoma Retinoblastoma Rhabdomyosarcoma Wilms tumor... 

The treatment of Hodgkin s disease also illustrates the use of combined modalities, that is, radiation plus chemotherapy. The combined modality approach to several childhood tumors (e.g., Ewing s sarcoma, Wilms tumor, and rhabdomyosarcoma) has dramatically increased the cure rates for these diseases. 

Dactinomycin is used in curative combined treatment of Wilms tumor, Ewing s sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents. 

Wilms tumor, Ewing s sarcoma, rhabdomyosarcoma, gestational choriocarcinoma, testicular tumors, lymphomas, melanomas Breast, ovarian, endometrial, bladder, thyroid cancers oat cell cancer of the lung Testicular, ovarian germ cell cancers, small-cell lung cancer, acute myelogenous and lymphoblastic leukemia... 

Unlabeled Uses Adrenocortical, bladder, cervical, endometrial, prostatic, testicular carcinomas Ewing s sarcoma multiple sclerosis non-small cell, small cell lung cancer organ transplant rejection osteosarcoma ovarian germ cell, primary brain, trophoblastic tumors rheumatoid arthritis soft tissue sarcomas systemic dermato-myositis systemic lupus erythematosus Wilms tumor... 

Wilms tumor (children) Surgery, radiotherapy, chemotherapy... 

LCLs derived from targeted populations have been utilized to evaluate genetic susceptibility to radiation sensitivity (9), sensitivity to mitomycin C in patients with Wilms tumor (10), and camptothecin-induced apoptosis (11). These cell lines have been useful for studying bleomycin-induced chromatid breaks and oxidant-induced apoptosis (12)... 

Cyclophosphamide Same as above Breast cancer, ovarian cancer, non-Flodgkin s lymphoma, CLL, soft tissue sarcoma, neuroblastoma, Wilms tumor, rhabdomyosarcoma Nausea and vomiting ... 

Doxorubicin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks inhibits topoisomerase II intercalates into DNA Breast cancer, Hodgkin s and non-Hodgkin s lymphoma, soft tissue sarcoma, ovarian cancer, non-small cell and small cell lung cancer, thyroid cancer, Wilms tumor, neuroblastoma Nausea, red urine (not hematuria) Cardiotoxicity (see text), alopecia, myelosuppression, stomatitis... 

Vincristine Inhibits mitosis ALL, Hodgkin s and non-Hodgkin s lymphoma, rhabdomyosarcoma, neuroblastoma, Wilms tumor None Neurotoxicity with peripheral neuropathy, paralytic ileus, myelosuppression, alopecia, SIADH... 

Vincristine has been effectively combined with prednisone for remission induction in acute lymphoblastic leukemia in children. It is also active in various hematologicmalignancies such as Hodgkin s and non-Hodgkin s lymphomas, and multiple myeloma, and in several pediatric tumors including rhabdomyosarcoma, neuroblastoma, Ewing s sarcoma, and Wilms tumor. 

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