Neuroblastoma development

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

Germinder H, Sagi-Assif O, Goldberg L, et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol 2001 167 4747-4757. 

Humanized and chimerized MAbs have been developed for the treatment of non-Hodgkin lymphoma, renal cell carcinoma, ovarian carcinoma, breast cancer, melanoma, and neuroblastoma [117,119,120,123,124]. Patients with relapsed or refractory myeloid leukaemias that have been treated with HuM95, did not develop significant HAMA responses [59]. 

The implementation of animal test protocols in the 1980s has been accompanied by the development of a host of alternative methods to study adverse effects of chemicals on reproductive and developmental parameters. For example, rat whole embryo culture stems from the seventies (16), as does the rat limb bud organ culture (17) and rat limb bud and brain micromass was developed in the eighties (18). An elegant nonvertebrate alternative model used regeneration of polyps of Hydra atUnuata from dissociated cells (19). Animal-free in vitro alternatives include those employing the proliferation of a human embryonic palatal mesenchymal cell line (20), the attachment of a mouse ovarian tumor cell line (21), and the differentiation of a neuroblastoma cell line (22) and a embryonal carcinoma cell line (23). Various overviews of methods have been published over the years (24). The predictability of... 

Other BZP derivatives are being investigated for possible therapeutic uses in depression, other psychiatric illnesses, epilepsy or seizure disorders, pain, and inflammatory diseases. Phenylpiperazine derivatives were developed to target specific tumors known as neuroblastomas. As of April 2002, no piperazines were being used for these conditions. 

Development of Fab fragments of anti-GD2 immunoliposomes entrapping doxorubicin for experimental therapy of human neuroblastoma, Cancer Lett., 197, 199-204. 

Neuroblastoma Liver metastases develop with extreme rapidity within the first 6-9 months of life. The general condition is not compromised until later. This metastatic spread is a result of a sympathogonioma which has its origin in the adrenal medulla or autonomic ganglia. Such a clinical picture is also termed Pepper s syndrome (W. Pepper, 1901). 

In one case of first-trimester exposure to cyclophosphamide in a woman pregnant with twins, the male twin was born with multiple congenital abnormalities and developed papillary thjroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age the female twin was unaffected (70). 

A 12-year-old girl with neuroblastoma and normal renal function developed severe hypercalcemia while receiving isotretinoin 160 mg/m /day (61). Her hypercalcemia resolved with hydration, diuretic therapy, and temporary withdrawal of isotretinoin. Despite a dosage reduction to 80 mg/m /day, severe hypercalcemia recurred during the next treatment cycle. Further treatment with isotretinoin was made tolerable by shortening the duration of the remaining cycles. 

A 5-year-old boy with a neuroblastoma was treated in the same way. On day 105 after bone-marrow transplantation he developed hypertension (BP 140/92 mmHg), hematuria, proteinuria, and a raised serum creatinine. His hemoglobin and platelet count fell. His urine contained protein 800 mg/1, a few hyaline casts, and 25-30 erythrocytes per high-power field. When nephritis developed, cw-retinoid acid was withdrawn. He gradually improved, and his urine cleared of casts, erythrocytes, and protein within 4 weeks. 

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