Delayed elimination of methotrexate associated with piperacillin administration.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
F Bessho
Publications and source records attributed to F Bessho.
[Brief history and future prospects of treatment of childhood acute lymphocytic leukemia].
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Adolescent↗
[Alterations of the p53 gene and clinical features in childhood acute lymphoblastic leukemia].
Correlations between alterations of the p53 gene and clinical features were examined in childhood acute lymphoblastic leukemia (ALL). We analyzed 147 patients and 38 cell lines for p53 mutations within exons 5 to 9 (2 to 11 in some of them) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. p53 gene mutations were found in 3 of 62 (5%) patients at diagnosis, 1 of 14 (7%) patients at relapse, and 13 of 20 (65%) cell lines in T-ALL, 2 of 20 (10%) patients at diagnosis, 4 of 4 (100%) patients at relapse, and 4 of 5 (80%) cell lines in t(1;19)-ALL, 1 of 23 (4%) patients at diagnosis, 2 of 22 (9%) patients at relapse, and 5 of 12 (42%) cell lines in common ALL other than t(1;19) or t(9;22)-ALL and 3 of 3 (100%) patients at diagnosis in B-ALL. In t(1;19)-ALL, p53 gene alterations were associated with a poor prognosis. The patients with p53 mutations had a trend towards poor prognosis in childhood ALL without B-ALL. p53 gene mutation is not always associated with the current prognostic factors. This alteration may become one of the important prognostic factors, if the detection of a small number of the leukemic cells with the p53 gene mutation would be possible.
Adolescent↗
Effects of mass screening on age-specific incidence of neuroblastoma.
Using data from the Japan Children's Cancer Registry, we estimated the age-specific incidence rates of neuroblastoma. Before the neuroblastoma screening program started in 1985, the age-standardized incidence rates of neuroblastoma ranged from 7.5 to 9.1 x 10(-6) for children under 15 years of age. After the introduction of the screening program, the annual incidence rate rose to 19.5 x 10(-6). The annual incidence rate for neuroblastoma in children under 1 year of age was 150.60 x 10(-6) in the years 1989 to 1992, whereas the incidence rates only varied between 23.6 and 34.13 x 10(-6) in the 3 preceding 5-year periods. This increase in incidence for infants was accompanied by a minor decrease in incidence for children 2 to 3 years of age. However, this decrease may only partly explain the large increase in incidence for infants. Therefore, we suggest that screening may result in the detection of otherwise spontaneously regressing tumors. It is urgent to determine the contribution of screening to decreasing mortality before deciding whether this screening program should be continued.
Age Factors↗
Infrequent mutations of the TP53 gene and no amplification of the MDM2 gene in hepatoblastomas.
We have investigated the mutation of the TP53 gene in hepatoblastomas (HBLs) by using polymerase chain reaction-single strand conformation polymorphism and direct sequencing in 38 HBL tumor samples and in two HBL cell lines. We detected the TP53 gene mutation in an anaplastic hepatoblastoma cell line, but no aberration of the TP53 gene (exons 5-9) was found in tumor samples and in the other HBL cell line. The mutation of the cell line was a missense mutation from GAC (asparagine) to CAC (histidine) at codon 281, which was different from the G-to-T transversion of codon 249 that is frequently found in adult hepatocellular carcinomas (HCCs). In addition, we performed Southern blot analysis of the MDM2 gene, but we did not find MDM2 gene amplification in 19 cases tested. Our results suggest that, in contrast to the findings in HCCs in adults, TP53 gene aberrations are not involved in the development or progression of HBLs in children.
Adult↗
Acidic catecholamine metabolites and 5-hydroxyindoleacetic acid in urine: the influence of diet.
Concentrations of vanillylmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), vanillic acid (VA) and 5-hydroxyindoleacetic acid (5-HIAA) in urine from healthy subjects were determined by a high-performance liquid chromatography system with a mixed-mode (C18/anion-exchange) column and an 8-channel electrochemical detector, in order to study the influence of diet, diurnal variation and age. The urinary excretion of 5-HIAA increased significantly after eating banana, pineapple, tomato, kiwi fruit and walnut. An increase in the urinary excretion of DOPAC and HVA after eating banana and that of VA after taking vanilla was also noted. The urinary excretion of VMA was not significantly influenced by any of the foods examined. The urinary excretion of 5-HIAA in the first-morning urine increased beyond the upper limit of the reference value when banana was taken at 2000 h the previous day. The excretion of all metabolites in the second-morning urine in the fasting state was within respective reference ranges. Diurnal variation of the excretion of VMA, DOPAC, HVA and 5-HIAA in urine was relatively small, but that of VA was large. The concentrations (mmol/mol creatinine) of VMA, DOPAC, HVA, 5-HIAA and VA in the first-morning urine from healthy subjects increased from 7 days after birth to 1 year and then decreased to adult levels at 13 years of age.
3,4-Dihydroxyphenylacetic Acid↗
Homozygous deletions of p16/MTS1 and p15/MTS2 genes are frequent in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood.
We analyzed 60 B precursor acute lymphoblastic leukemia (ALL) primary samples and 15 cell lines for homozygous deletions of p16 and p15 genes and mutations of p16 gene. These included five cell lines and 13 primary samples with the t(1;19)(q23;pl3), and eight primary samples with the t(9;22)(q34;qll). Of 10 cell lines without t(1;19), homozygous deletion of both p16 and p15 genes was found in eight cell lines (80%), and a rearrangement of p16 in one cell line (10%). In contrast, only one (20%) of the five cell lines with t(1;19) showed homozygous deletion or rearrangement of p16/p15 gene. Thirteen of 60 (22%) primary samples demonstrated p16 gene homozygous deletion. No case with t(1;19) showed homozygous deletion of p16 gene (0/13, 0%), while cases without t(1;19) showed considerable incidence of p16 gene homozygous deletion (13/47, 28%). These results suggest that the incidence of deletions of p16 gene differs according to the subtypes of B precursor ALL. We also compared the frequency of p16 gene homozygous deletion between the patients at diagnosis and at relapse. Nine of 45 (20%) samples at diagnosis and four of 22 (18%) samples at relapse showed p16 homozygous deletions. The similarity of the rate in these two groups raises the question of the role of p16 gene in progression of B precursor ALL. Mutations were found in three of the primary cases (5%); the mutations included two nonsense mutations at codon 72 and one missense mutation at codon 98. All the mutations found in this study were heterozygous, and the clinical relevance of p16 gene mutation is yet to be determined in these case
Base Sequence↗
Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia.
We have analyzed the frequency and clinical significance of the MLL gene rearrangements in 42 cases of infant acute leukemias; including 37 cases of acute lymphoblastic leukemia (ALL) and five cases of acute myeloid leukemia (AML). MLL gene rearrangements were found in 27 of the 37 ALL cases (73 percent), and in all five AML cases. Cytogenetic studies showed 11q23 abnormalities in 24 of 27 ALL cases with MLL gene rearrangements. MLL gene rearrangements were significantly correlated with absence of CD10 expression and poor prognosis, but not with age under 6 months, hyperleukocytosis, myeloid-associated antigen expression, or CNS leukemia. The 3-year overall survival rate for ALL cases with MLL gene rearrangements was 5.3 +/- 5.2 percent, compared with 88.9 +/- 10.5 percent for cases with germline MLL (P=0.0001). Absence of CD10 expression was also associated with poor prognosis (9.9 +/- 6.6 percent vs 85.7 +/- 13.2 percent, P = 0.0003). Of the five AML cases, three have remained alive for 27 months to 67 months. These findings suggest that infant ALL with MLL gene rearrangement is strongly associated with poor prognosis. We consider that infant ALL should be treated on different chemotherapy protocols according to the presence or absence of MLL gene rearrangement.
Antigens, CD↗
EWS-FLI-1 and EWS-ERG chimeric mRNAs in Ewing's sarcoma and primitive neuroectodermal tumor.
The t(11;22)(q24;q12) and t(21;22)(q22;q12) are specific chromosomal translocations found in the Ewing family of tumors including ES, PNET and Askin tumors. In these translocations, the amino-terminal portion of the EWS gene located in 22q12 fuses to the carboxyl-terminal portion of the FLI-1 gene located in 11q24 or the ERG gene located in 21q22, which belong to the ets oncogene superfamily of transcription activators. We investigated the chimeric mRNAs of 15 ESs (7 cell lines and 8 tumor samples) and 7 PNETs (3 cell lines and 4 tumor samples) using the RT-PCR method and sequencing. We detected 2 types of EWS-ERG chimeric mRNA in 2 ES cell lines and 1 PNET tumor sample in addition to 4 types of EWS-FLI-1 chimeric mRNA in 11 ESs (4 cell lines and 7 tumor samples) and 4 PNETs (2 cell lines and 2 tumor samples). There seemed to be no association between the type of chimeric mRNA and clinical features such as sex, age, primary site and histopathology of the patients. All of the chimeric mRNAs are generated from in-frame junctions and are thought to encode fusion proteins that may be the molecular mechanism involved in the Ewing family of tumors.
Adolescent↗
Liver function studies in children with acute lymphocytic leukemia after cessation of therapy.
We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood.
Adolescent↗
Primary chemotherapy for children with rhabdomyosarcoma of the 'special pelvic' sites: is preservation of the bladder possible?
Twenty-one children with rhabdomyosarcoma involving the "special pelvic" sites, defined as such occurring in the bladder, prostate, vagina and uterus, were treated with primary surgery between 1969 and 1977, and with primary chemotherapy beginning in 1978. Among 11 patients in the latter group who were placed in Clinical Group III (according to the classification of the US Intergroup Rhabdomyosarcoma Study (IRS), six showed partial response (PR) and underwent tumorectomy by radical surgery an average of 6 months after the start of treatment, and three showed complete response (CR) and were treated with further chemotherapy in the hope that cystectomy could be avoided. However, in the latter group, the tumor recurred (39 months, 35 months, and 27 months later), and all eventually underwent total cystectomy. Seven of the nine long-term survivors underwent total cystectomy and have premanent urinary-cutaneous stomas. Two had tumor-free bladders, but function was impaired in one because of the effect of irradiation. Normal function was preserved in only one patient in the series, whose tumor was located at the dome of the bladder. To preserve bladder function in children with rhabdomyosarcoma in these sites, more effective forms of chemotherapy will be required.
Antineoplastic Combined Chemotherapy Protocols↗
Pulmonary carcinoma associated with hamartoma in an 11-year-old boy.
PURPOSE: We describe a poorly differentiated adenocarcinoma of the lung in an 11-year-old boy who had had a pulmonary hamartoma for at least 8 years. CONCLUSIONS: A hamartoma, even if clinically silent, may lead to the development of malignant tumors on rare occasions.
Adenocarcinoma↗
Mass screening in Japan increased the detection of infants with neuroblastoma without a decrease in cases in older children.
Analysis of data from the Kanto-Ko-Shin-Etsu Branch of the Japan Children's Cancer Registry revealed that mass screening for neuroblastoma increased the detection of cases in infants younger than 1 year from about 25% before screening to about 50%, and the percentage of neuroblastomas among all pediatric cancers almost doubled, from approximately 10% to 19.3%. However, when the cases found on screening were subtracted, the numbers after the onset of mass screening were similar to those before screening. It is likely that neuroblastoma mass screening has identified a unique type of tumor, which may not be recognized without mass screening, rather than that it has contributed to the earlier diagnosis of tumors in older children.
Age Factors↗
Malignant cell detection in Burkitt's lymphoma using third-complementarity-determining region (CDRIII), clone-specific probe developed by sequencing DNA from stored slides.
The DNA sequence of the third-complementarity-determining region (CDRIII) of the immunoglobulin heavy chain (IgH) gene in a case of Burkitt's lymphoma was determined by polymerase chain reaction (PCR) using template DNA extracted from a smear stored at room temperature for more than one year. The DNA sequence obtained from the stored slide was compared with that of DNA from a frozen lymph node biopsied at the initial presentation. The sequences were shown to be identical, implying that DNA from a smear on a stored slide can be used as a source of DNA for PCR amplification, sequencing, and development of a clone-specific probe. Using oligonucleotides generated from one of the CDRIII sequences of the IgH gene as molecular probes, a retrospective study for the malignant clone on the smears was carried out. Malignant cells were detectable in the peripheral blood at an early stage of bone marrow relapse but not in the peripheral blood or bone marrow at the initial presentation. No malignant clone was detected in the bone marrow when testicular infiltration was diagnosed by examination of a pathological specimen. Thus, the technique permits molecular analysis of hematologic malignancies of B-cell lineage in cases where fresh or frozen specimens are not available.
Base Sequence↗
Improved prognosis of acute nonlymphocytic leukemia in children: results of the 12th-ANLL protocol of Tokyo Children's Cancer Study Group.
Thirty-one children with ANLL were treated using the 12th-ANLL Protocol of the Tokyo Children's Cancer Study Group incorporating an ACMP 2-step regimen. Induction therapy consisted of two 4-day courses of adriamycin (ADR) and cytosine arabinoside (ARA-C) given with a 7-day interval. Those patients who achieved remission were given one more course as early intensification. Late intensification consisted of a 5-day course of ARA-C and one dose of ADR which was repeated until the cumulative dosage of ADR reached 465 mg/m2. After this point, treatment was divided into 2 courses. Both courses included ARA-C and one course had achlacinomycin in addition. Twenty-seven children (87%) attained remission after one or two courses of induction therapy. Kaplan-Meyer analysis revealed that the continuous complete remission rate and event-free survival were 71% and 51%, respectively, 5 years after diagnosis. Toxicity was minimum with only one death during the remission. These results are encouraging and warrant further trials.
Adolescent↗
Late effects of childhood acute leukemia and its treatment.
Late effects of childhood acute leukemia and its treatment were studied in 776 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.
Adolescent↗
Treatment of acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group--preliminary results of L84-11 protocol.
The Tokyo Children's Cancer Study Group (TCCSG) has performed prospective randomized controlled studies since 1984 for childhood acute lymphoblastic leukemia (ALL). Four hundred and ninety-eight newly diagnosed patients were treated with 5 different regimens designated as S1, S2 for a standard risk group (SRG), H1 and H2 for a high risk group (HRG) and HEX for an extremely high risk group of patients. We added intermediate-dose methotrexate as early intensification therapy in the S2 and H2 groups to reduce extramedullary and medullary relapses. Event-free survival of all patients at 4 years 6 months from the start of this regimen (median follow-up period 32 months) was 67.5%. The CNS relapse rate was significantly decreased to 2.2% compared to previously reported studies and our own experience. There were some unexpected complications of the CNS such as myelopathy and/or leukoencephalopathy. For the SRG early ID-MTX seemed to be useful to improve the prognosis, but triple intrathecal injections (TIT) should be limited in number. The 24Gy cranial irradiation (CRX) was effective but possibly excessive for the HRG. As evidenced by the success of the HEX group regimen, more intensive multi-drug consolidation in the early post-remission phase might be necessary to improve further the prognosis and to make it possible to shorten the treatment periods.
Antineoplastic Combined Chemotherapy Protocols↗
Clonal analysis of transient myeloproliferative disorder in Down's syndrome.
Three Down's syndrome patients with transient myeloproliferative disorder were studied for clonality of the proliferating blast cells using the X chromosome-linked polymorphic gene phosphoglycerate kinase, immunoglobulin heavy chain (IgH) gene and T-cell antigen receptor (TCR) (beta, gamma, delta) genes. None of the three cases showed rearrangements of IgH, TCR beta, gamma, or delta genes, indicating the non-lymphoid nature of the proliferating blast cells. The X chromosome inactivation pattern showed that the cells in the blast population in all of the three cases of transient myeloproliferative disorder were clonal. These data suggest that at least some of this disorder can be due to a spontaneously regressing clone of malignant cells.
Adolescent↗