The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have re... more The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been pr...
The common gamma chain, which was originally identified as a component of interleukin-2 receptors... more The common gamma chain, which was originally identified as a component of interleukin-2 receptors (IL-2R), plays a key role in differentiation of T lymphocytes and natural killer (NK) cells. In the present study, cDNA of the porcine common gamma chain gene and its genomic DNA were molecularly cloned and characterized. The porcine common gamma chain gene was found to consist of 8 exons, spanning approximately 3.7 kb, and to encode a 368-amino acid polypeptide. The amino acid sequence showed 82.4%, 71.1%, 86.1%, and 84.8% similarities with that of human, murine, bovine, and canine chains, respectively. The common gamma chain gene was assigned to swine chromosome Xq13 by FISH analysis and was consistent with the result of radiation hybrid (RH) mapping. When various porcine tissues were examined for the expression of this gene, the expression was observed in lymphocytes and lymphocyte-related tissues. Since GATA, T cell factor-1 (TCF-1), Ets-1, activated protein2 (AP-2), and Ikaros2 binding motifs were demonstrated in the 5' upstream region of this gene, promoter activity was investigated using luciferase gene as a reporter. The results indicate that the Ets-1 binding motif in the segment from -95 to -59 (major transcription initiation site: +1) was an essential cis-acting regulatory element for the common gamma chain gene in lymphoid cells.
Virchows Archiv a Pathological Anatomy and Histopathology, Feb 1, 1987
Adult and fetal human kidneys were investigated for the reactivities of monoclonal antibodies, BA... more Adult and fetal human kidneys were investigated for the reactivities of monoclonal antibodies, BA-1, BA-2 and BA-3 against human leukocytes. In developing metanephros, their reactivities changed reflecting the stage of nephrogenesis. Thus BA-1 stained both metanephric blastema and ureteric bud. Glomerular and proximal tubular development was characterized by the disappearance of BA-1 reactive antigen and the appearance of CALLA defined by BA-3. Immuno-electron-microscopically CALLA was solely located on the glomerular epithelial membrane and on the microvilli of the proximal tubules. BA-2 constantly stained ureteric bud-derived tissues. These observations were applied for the analysis of histogenesis of Wilms' tumour. Tumour blastema of the classical type reacted only with BA-1. Epithelial components in the classical as well as the epithelial type reacted both with BA-1 and BA-2. CALLA was only detectable in glomeruloid and the connecting tubular structures, while these were unstained by BA-1. Stromal components in the classical and the sarcomatous type did not express any of these antigens. Staining patterns were identical in surgically removed and xenotransplanted tumours. These studies establish that each component of Wilms' tumour can clearly be interpreted regarding its histogenesis and that epithelial components corresponding to proximal tubules are identified in Wilms' tumour.
A previously healthy 8-year-old Japanese boy developed nephrotic syndrome during the course of er... more A previously healthy 8-year-old Japanese boy developed nephrotic syndrome during the course of erythema infectiosum due to human parvovirus B19 (PVB19) infection. A renal biopsy showed mesangiocapillary proliferative glomerulonephritis with immune complex deposits associated with PVB19 virus. His renal involvement improved spontaneously.
The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal ... more The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.
Dietary bioflavonoids are secondary metabolites of plants that are known to have a variety of bio... more Dietary bioflavonoids are secondary metabolites of plants that are known to have a variety of bio-effects, including anti-cancer activity. In this study, we examined the effects of flavonoids on the growth of human leukemia cells and found that certain flavonoids induce apoptosis in a variety of human leukemia cells. The apoptosis induced by bioflavonoids was dose-dependent and was accompanied by
Raft microdomains are glycolipid-enriched microdomain scaffolding molecules involved in signal tr... more Raft microdomains are glycolipid-enriched microdomain scaffolding molecules involved in signal transduction. The binding of Shiga toxin to globotriaosyl ceramide in raft microdomains of the human renal tubular cell line ACHN causes temporal activation of Src-kinase Yes. To study the downstream signaling mechanism proceeding to the activation of Yes, we raised monoclonal antibodies (MAbs) against raft microdomains. The MAbs were screened on the basis of, first, binding to raft microdomains with dot-blot immunostaining, second, intracellular localization of the epitope by flowcytometry after permeabilization, and third, translocation of the antigen molecules after Stx treatment by immunohistochemical staining. Raft.1 MAb bound to the molecules that accumulated to the particular region near the nucleus after Stx treatment. Two-dimensional Western blotting and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed that the antigen molecule is GTP binding protein beta subunits 1 and 2 (Gbeta1 and 2). That Raft.1 recognized Gbeta1 and 2 was further confirmed by the reactivity to recombinant Gbeta1 and 2 proteins. To our knowledge, this is the first report of production of a MAb recognizing Gbeta1 and 2. Because Gbeta1 and 2 are highly conserved all through organisms and are deeply involved in signal transduction, Raft.1 is expected to be utilized frequently in research.
International journal of clinical oncology, Jan 30, 2015
The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian cou... more The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan. A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis. One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-yea...
The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have re... more The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been pr...
The common gamma chain, which was originally identified as a component of interleukin-2 receptors... more The common gamma chain, which was originally identified as a component of interleukin-2 receptors (IL-2R), plays a key role in differentiation of T lymphocytes and natural killer (NK) cells. In the present study, cDNA of the porcine common gamma chain gene and its genomic DNA were molecularly cloned and characterized. The porcine common gamma chain gene was found to consist of 8 exons, spanning approximately 3.7 kb, and to encode a 368-amino acid polypeptide. The amino acid sequence showed 82.4%, 71.1%, 86.1%, and 84.8% similarities with that of human, murine, bovine, and canine chains, respectively. The common gamma chain gene was assigned to swine chromosome Xq13 by FISH analysis and was consistent with the result of radiation hybrid (RH) mapping. When various porcine tissues were examined for the expression of this gene, the expression was observed in lymphocytes and lymphocyte-related tissues. Since GATA, T cell factor-1 (TCF-1), Ets-1, activated protein2 (AP-2), and Ikaros2 binding motifs were demonstrated in the 5' upstream region of this gene, promoter activity was investigated using luciferase gene as a reporter. The results indicate that the Ets-1 binding motif in the segment from -95 to -59 (major transcription initiation site: +1) was an essential cis-acting regulatory element for the common gamma chain gene in lymphoid cells.
Virchows Archiv a Pathological Anatomy and Histopathology, Feb 1, 1987
Adult and fetal human kidneys were investigated for the reactivities of monoclonal antibodies, BA... more Adult and fetal human kidneys were investigated for the reactivities of monoclonal antibodies, BA-1, BA-2 and BA-3 against human leukocytes. In developing metanephros, their reactivities changed reflecting the stage of nephrogenesis. Thus BA-1 stained both metanephric blastema and ureteric bud. Glomerular and proximal tubular development was characterized by the disappearance of BA-1 reactive antigen and the appearance of CALLA defined by BA-3. Immuno-electron-microscopically CALLA was solely located on the glomerular epithelial membrane and on the microvilli of the proximal tubules. BA-2 constantly stained ureteric bud-derived tissues. These observations were applied for the analysis of histogenesis of Wilms' tumour. Tumour blastema of the classical type reacted only with BA-1. Epithelial components in the classical as well as the epithelial type reacted both with BA-1 and BA-2. CALLA was only detectable in glomeruloid and the connecting tubular structures, while these were unstained by BA-1. Stromal components in the classical and the sarcomatous type did not express any of these antigens. Staining patterns were identical in surgically removed and xenotransplanted tumours. These studies establish that each component of Wilms' tumour can clearly be interpreted regarding its histogenesis and that epithelial components corresponding to proximal tubules are identified in Wilms' tumour.
A previously healthy 8-year-old Japanese boy developed nephrotic syndrome during the course of er... more A previously healthy 8-year-old Japanese boy developed nephrotic syndrome during the course of erythema infectiosum due to human parvovirus B19 (PVB19) infection. A renal biopsy showed mesangiocapillary proliferative glomerulonephritis with immune complex deposits associated with PVB19 virus. His renal involvement improved spontaneously.
The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal ... more The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.
Dietary bioflavonoids are secondary metabolites of plants that are known to have a variety of bio... more Dietary bioflavonoids are secondary metabolites of plants that are known to have a variety of bio-effects, including anti-cancer activity. In this study, we examined the effects of flavonoids on the growth of human leukemia cells and found that certain flavonoids induce apoptosis in a variety of human leukemia cells. The apoptosis induced by bioflavonoids was dose-dependent and was accompanied by
Raft microdomains are glycolipid-enriched microdomain scaffolding molecules involved in signal tr... more Raft microdomains are glycolipid-enriched microdomain scaffolding molecules involved in signal transduction. The binding of Shiga toxin to globotriaosyl ceramide in raft microdomains of the human renal tubular cell line ACHN causes temporal activation of Src-kinase Yes. To study the downstream signaling mechanism proceeding to the activation of Yes, we raised monoclonal antibodies (MAbs) against raft microdomains. The MAbs were screened on the basis of, first, binding to raft microdomains with dot-blot immunostaining, second, intracellular localization of the epitope by flowcytometry after permeabilization, and third, translocation of the antigen molecules after Stx treatment by immunohistochemical staining. Raft.1 MAb bound to the molecules that accumulated to the particular region near the nucleus after Stx treatment. Two-dimensional Western blotting and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed that the antigen molecule is GTP binding protein beta subunits 1 and 2 (Gbeta1 and 2). That Raft.1 recognized Gbeta1 and 2 was further confirmed by the reactivity to recombinant Gbeta1 and 2 proteins. To our knowledge, this is the first report of production of a MAb recognizing Gbeta1 and 2. Because Gbeta1 and 2 are highly conserved all through organisms and are deeply involved in signal transduction, Raft.1 is expected to be utilized frequently in research.
International journal of clinical oncology, Jan 30, 2015
The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian cou... more The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan. A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis. One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-yea...
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Papers by Junichiro Fujimoto