PURPOSE: To elucidate the efficacy of intensive induction and consolidation chemotherapy regimens (Study Group of Japan for Advanced Neuroblastoma [JANB] 85) for patients with advanced neuroblastoma aged 1 year or older. PATIENT AND METHODS: One hundred fifty-seven patients with newly diagnosed advanced neuroblastoma were entered into this study between January 1985 and December 1990. Eligible patients were 12 months old or older with stage III or IV disease. The patients first received six cyclic courses of intensive induction chemotherapy (designated regimen A1) consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydro-pyranyl Adriamycin (pirarubicin; 40 mg/m2), and cisplatin (90 mg/m2). The patients were further treated with three different consolidation protocols: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea, dacarbazine, and bone marrow transplantation. RESULTS: Overall survival rates for patients with stage III disease without reference to the consolidation protocols were 80.8%, 76.9%, and 66.3% at 2, 5, and 10 years, respectively. The overall survival rates for patients with stage IV disease were 58.8%, 34.4%, and 28.9% at 2, 5, and 10 years, respectively. There were no statistically significant differences between the three consolidation treatment groups. Patients who did not achieve complete remission (CR) with induction chemotherapy and surgery all died, suggesting that CR is essential for the cure of advanced neuroblastoma. The overall 5-year survival rate of the 24 patients with N-myc amplified stage III and IV disease was 33.3%, and the longest survival time of a relapse-free patient was 103 months. CONCLUSION: The intensive induction chemotherapy regimen used in this study may be of significant value in increasing the CR rate and survival for patients with N-myc amplified and nonamplified advanced neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Direct evidence of a connection between autotransplanted microvessel fragments and the host microvascular system.

There are no reports on the autologous transplantation and patency of microvessels in living tissue. We autotransplanted microvessel fragments (Mvf) labeled with DiI-Ac-LDL into the peritoneum and then observed the peritoneum for 7 days postoperatively with a conventional fluorescence or laser scanning confocal microscope. We illustrated a neomicrovascular network of transplanted Mvf labeled with DiI-Ac-LDL in the peritoneum with both a fluorescence and a laser scanning confocal microscope. Furthermore, we demonstrated not only the existence of erythrocytes in the lumina of transplanted DiI-Ac-LDL-labeled Mvf, but also the presence of India ink perfused through the superior mesenteric artery in the lumina of the labeled Mvf. This evidence directly suggests that transplanted Mvf can survive and proliferate to connect adjacent microvascular branches of the superior mesenteric artery in the very early phase of wound healing. Moreover, these findings imply that implantation of Mvf in the microvascular ischemic circulatory tissue might accelerate angiogenesis to reconstitute a new microvascular network connecting to the nearby host microvascular system, which ultimately improves microcirculation.

Anastomosis, Surgical↗

PubMedDate not supplied

Renin production in congenital mesoblastic nephroma in comparison with that in Wilms' tumor.

The case of an infant with congenital mesoblastic nephroma and associated reninism is presented. The patient was a 39-day-old boy who presented with a left abdominal mass and mild hypertension (112/70 mm Hg). Both plasma renin activity (PRA) and plasma total renin concentration (PTRC) were elevated; the PTRC value of 1458 pg/mL of this case was the highest we had seen in patients with childhood renal tumors. The tumor was successfully removed and histologically confirmed as a congenital mesoblastic nephroma (cellular variant). The patient's PRA and PTRC returned to normal after nephrectomy. Indirect immunoperoxidase staining showed renin localized predominantly in the juxtaglomerular apparatuses adjacent to the glomeruli entrapped by the tumor. No positive staining was seen in the tumor cells. These findings indicate that the entrapped glomeruli may play a significant role in producing renin. More important, PTRC was extremely high compared to the moderate increase of PRA and to the mild elevation of blood pressure. The mechanism of renin production by childhood renal tumors is discussed, and the importance of studying inactive renin and total renin is emphasized.

Humans↗

PubMedDate not supplied

Antitumor effects of fotemustine and busulfan against a human neuroblastoma xenograft.

We examined whether or not fotemustine, a new nitrosourea derivative, and busulfan, an agent already clinically used, are effective against human neuroblastoma, using a human neuroblastoma xenograft model designated TNB9. The maximum inhibition rate (MIR) of fotemustine against the TNB9 model was 44.6% with a total dose of fotemustine of 75 mg/kg, indicating that fotemustine is not effective against TNB9. The MIR of busulfan against the same model was 26.7% when a total dose of 135 mg/kg was administered orally to nude mice. Busulfan was also suspended in carboxy-methylcellulose, and was administered intraperitoneally. The MIRs were 19.4% and 36. 4% when busulfan was administered intraperitoneally at a total dose of 40 mg/kg and 60 mg/kg, respectively. The total doses of 40 mg/kg and 60 mg/kg did not show any adverse effects on mice, but were found to be ineffective against TNB9, indicating that busulfan might not be an effective chemotherapeutic agent against human neuroblastoma.

Administration, Oral↗

PubMedDate not supplied

A polyclonal antibody against synthetic peptide conserved in N-Myc protein reacts with water-soluble recombinant N-Myc protein.

The importance of determining the N-Myc protein has been emphasized in neuroblastoma. We attempted to obtain a water-soluble N-Myc protein, and an antibody highly specific for the N-Myc protein. A plasmid was constructed from partial exons 2 and 3 of the N-myc gene, and expressed in Escherichia coli by isopropyl-beta,-D-thiogalactopyranoside. Newly obtained N-Myc (rN-Myc) was water-soluble with a M.W. of 38 kDa. An N-Myc-specific peptide, GVAPPRPGG RQTSGGDH, was used to raise an antibody. Specificity of the obtained antibody was confirmed and we found the rN-Myc protein reacts positively with the anti-N-Myc IgG raised here. The rN-Myc protein and the anti-N-Myc IgG obtained are expected to be used in an ELISA for N-Myc.

Amino Acid Sequence↗