1/4. Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents.The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children. ( info) |
2/4. Pleomorphic (anaplastic) neuroblastoma in nude mice.Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6 years, were transplanted into nude mice. Two noteworthy observations were made. In one case, the transplanted tumor gave rise to a soft-tissue sarcoma. Moreover, in both cases hepatic metastases were associated with a striking modification of murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei. The latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic (anaplastic) neuroblastoma cells. ( info) |
3/4. A familial hyperalphalipoproteinemia with low uptake of high density lipoproteins into peripheral lymphocytes.A patient with an extremely high level of high density lipoprotein (HDL)-cholesterol and HDLc-like particles in the serum is discussed. The patient was a 46-year-old female with a serum total cholesterol concentration of 382 mg/dl and HDL-cholesterol level of 214 mg/dl. The HDL-cholesterol levels of her mother, brother, sister and 2 of her daughters were 82 mg/dl, 82 mg/dl, 74 mg/dl, 82 mg/dl and 82 mg/dl, respectively (mean HDL-cholesterol levels of control subjects: 52 /- 6 mg/dl in males and 55 /- 8 mg/dl in females). Her serum apolipoprotein a-i and E levels were elevated. Zonal ultracentrifugal analysis of her serum lipoproteins showed that the increased level of HDL-cholesterol was mainly due to HDL2; HDLc-like particles were also recognized between the LDL and HDL fractions. The incorporation of the patient's HDL and HDLc-like particles into cultured HepG2 cells was almost the same as that of HDL (1.063 less than d less than 1.21) from normal control serum. The incorporation of normal control HDL into the patient's peripheral blood lymphocytes was markedly less than that into lymphocytes from normal controls. These findings are discussed in terms of the reason for hyperalphalipoproteinemia in this patient. ( info) |
4/4. Cytoplasmic liver cell inclusions--a typical feature of porphyria cutanea tarda--are absent in porphyria-related hepatic neoplasias.Crystalline cytoplasmic needle-shaped inclusions in hepatocytes are considered to represent a specific morphological feature of porphyria cutanea tarda (PCT) and experimental PCT-like porphyrias. The cytoplasmic inclusions, however, are absent in hyperplastic hepatic nodules and hepatocellular carcinomas arising in the course of these conditions. It is assumed that porphyrins and related substances accumulated in hyperplastic and neoplastic hepatic lesions differ from those found in non-neoplastic liver tissue: the highly carboxylated porphyrins are stored in both sites, the crystal-forming substance only in non-proliferating liver tissue. ( info) |