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2.
Bone Marrow Transplant ; 50(10): 1299-305, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26168068

ABSTRACT

Allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with relapsed follicular lymphoma (FL). Prospective studies of reduced-intensity conditioning (RIC) have revealed that chemosensitivity at allo-SCT is the most reliable predictor of outcome; however, limited data are available for progressive/refractory disease. We report here a retrospective analysis of RIC allo-SCT for patients with FL. The purpose of this study was to elucidate the role of allo-SCT for patients with relapsed/refractory FL. We analyzed 46 patients-11 (24%) transplanted in CR, 6 (13%) transplanted in PR and 29 (63%) with progressive/refractory disease. The estimated 5-year overall survival rate was 71.6% (95% confidence interval (CI), 51.5-84.5%). According to the disease status at transplantation, the 5-year survival rate was 80.7% (95% CI, 37.7-95.4%) in the patients with CR or PR and 66.1% (95% CI, 41.5-82.3%) in those with progressive/refractory disease (P=0.29). There were no differences in relapse/progression and non-relapse mortality between the patients with chemosensitive disease and progressive/refractory disease. Allo-SCT may be a valuable treatment option, even for patients with progressive/refractory FL.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Follicular/therapy , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Adult , Aged , Female , Humans , Lymphoma, Follicular/mortality , Male , Middle Aged , Retrospective Studies
4.
Neuroscience ; 137(1): 265-73, 2006.
Article in English | MEDLINE | ID: mdl-16289588

ABSTRACT

Neuropeptide W-23 and neuropeptide B are each an endogenous ligand of GPR7. GPR7 mRNA has been detected in regions of the cortex, the hippocampus, the hypothalamus and the spinal cord in the rat. GPR7 receptor has structural features in common with both opioid and somatostatin receptors. In the present study, the effects of intrathecal and i.c.v. application of neuropeptide W-23 and neuropeptide B on the level of mechanical allodynia induced by partial sciatic nerve ligation were tested in rats. The level of mechanical allodynia was measured using von Frey filaments. Intrathecal injection of either neuropeptide W-23 or neuropeptide B attenuated the level of mechanical allodynia in a dose dependent manner at a dose between 0.1 and 10 microg, but i.c.v. injection of either neuropeptide W-23 or neuropeptide B had no effect on the level of mechanical allodynia at a dose between 3 and 30 microg. The effect of intrathecal administration of either 10 microg of neuropeptide W-23 or 10 microg of neuropeptide B was not antagonized by i.p. injection of 1 mg/kg of naloxone. Immunohistochemical examination revealed that neuropeptide W-23 was expressed mainly in the small- to medium-sized neuronal profiles in the dorsal root ganglion and that partial sciatic nerve injury decreased the percentage of neuropeptide W-23-like immunoreactivity positive neuronal profiles that were labeled by IB4. These data suggest that neuropeptide W-23 is involved in the nociceptive transmission in spinal cord and that both spinally-applied neuropeptide W-23 and spinally-applied neuropeptide B produce anti-allodynic effects in the partial sciatic nerve ligation model in rat.


Subject(s)
Analgesics/administration & dosage , Neuralgia/drug therapy , Neuralgia/physiopathology , Neuropeptides/administration & dosage , Sciatic Neuropathy/physiopathology , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Ganglia, Spinal/metabolism , Immunohistochemistry , Injections, Intraventricular , Injections, Spinal , Ligation , Male , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled , Receptors, Neuropeptide/metabolism
6.
J Pediatr Surg ; 37(12): 1703-6, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12483635

ABSTRACT

PURPOSE: This study aims to assess the prognostic factors and optimal treatments for malignant germ cell tumors (MGCT) in childhood. METHODS: Among 117 MGCT, the clinical features were analyzed. Regarding the histology, there were 89 embryonal carcinomas, 13 dysgerminomas, 4 choriocarcinomas, and 11 others. The prognostic factors and treatments were assessed based on the 5-year survival rate. RESULTS: (1) Stage: 100% for stage I (n = 54), 75.0% for stage II (n = 4), 67.3% for stage III (n = 14), and 54.8% for stage IV (n = 33); Unknown: n = 12. (2) Primary site: 93.4% for the testis (n = 52), 86.7% for the ovary (n = 31), 56.9% for the sacrococcygeal (n = 21), and 60.6% for others (n = 12); unknown: n = 1. (3) Surgical intervention for primary tumor: 100% for stage I with a complete resection (n = 53), 78.4% for stage III, IV with a complete resection (n = 26), and 33.3% for stage III, IV with an incomplete resection (n = 21). (4) Type of chemotherapy for the stage III and IV: 83.9% for the PVB (cisplatin, vinblastin, bleomycin; n = 13), 66.7% for the VAC (vincristine, actinomycin D, cyclophosphamide; n = 6), and 47.1% for other regimens (n = 25). CONCLUSIONS: An early stage, a diagnosis under 1 year of age and a primary site in the gonads were favorable prognosis factors, whereas histologic findings of choriocarcinoma and liver or lung metastasis were unfavorable. Radical complete resection alone is a sufficient treatment for localized MGCT. The PVB regimen is optimal chemotherapy for advanced MGCT; however, high-risk cases still may require more aggressive treatment.


Subject(s)
Germinoma/diagnosis , Germinoma/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Female , Germinoma/mortality , Germinoma/secondary , Humans , Incidence , Infant , Infant, Newborn , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Male , Neoplasm Staging , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Rate , Testicular Neoplasms/diagnosis , Testicular Neoplasms/epidemiology , Testicular Neoplasms/surgery , Treatment Outcome
7.
Eur J Pediatr Surg ; 11(1): 19-23, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11370977

ABSTRACT

A hepatic portocholecystostomy (HPC) has been recommended to avoid postoperative cholangitis in the case of a patent distal extrahepatic bile duct (PDEBD) for the treatment of biliary atresia (BA). We investigated the efficacy and clinical problems of HPC in BA. The clinical records of eight patients with BA and PDEBD were reviewed. The diameter of the common bile duct was compared between the patients with BA and PDEBD and age-matched patients with neonatal hepatitis (NH). Five of 8 patients with PDEBD underwent HPC. One patient had to be converted to a cholecystojejunostomy because of common bile duct stenosis at 19 years of age. The other two patients underwent a reoperation by a hepatic portojejunostomy due to poor bile drainage after HPC. Another patient became jaundice-free one month after HPC, but died of sepsis due to bile leakage 3 months thereafter. The mean diameter of the common bile duct in BA with PDEBD was significantly smaller than that of NH (0.76 +/- 0.16 mm (n = 8) in BA vs. 1.90 +/- 0.39 mm (n = 11) in NH, p<0.01). HPC was thus found to be an excellent operative method for preventing postoperative cholangitis in BA, however, many clinical problems still need to be overcome for such a narrow distal duct.


Subject(s)
Biliary Atresia/surgery , Cholecystostomy , Portoenterostomy, Hepatic/methods , Biliary Atresia/pathology , Common Bile Duct/pathology , Constriction, Pathologic , Female , Humans , Infant , Male , Retrospective Studies
9.
Cancer Lett ; 166(1): 89-94, 2001 May 10.
Article in English | MEDLINE | ID: mdl-11295291

ABSTRACT

The amplification of the N-myc gene and a gain of the chromosome 17q arm correlate with an unfavorable outcome in patients with neuroblastoma. In this study, we determined the gene dosage of the N-myc gene (located at 2p24) and Survivin gene (located at 17q25) using the p53 gene (located at 17p13) as the internal control gene by the TaqMan polymerase chain reaction (PCR)-based gene dosage analysis in 25 neuroblastoma samples. Based on the assumption that the gene dosages of each gene of a normal individual lymphocytes are 1.0, 11 of the 25 cases with a corrected gene dosage of N-myc (N-myc/p53) of more than 2.0 had a more unfavorable prognosis than the 14 cases with a N-myc gene dosage of less than 2.0 (5-year survival rate: 18 vs. 71%, P<0.01). Ten of 25 cases with a corrected Survivin gene dosage (Survivin/p53) of more than 2.0 had a more unfavorable prognosis than the 15 cases with a Survivin gene dosage of less than 2.0 (5-year survival rate: 10 vs. 67%, P<0.01). This quantitative PCR system is considered to be useful for quickly and accurately evaluating the degree of malignancy of neuroblastoma in order to select the optimal treatment.


Subject(s)
Chromosomes, Human, Pair 17 , Gene Dosage , Genes, myc , Microtubule-Associated Proteins , Neuroblastoma/genetics , Neuroblastoma/mortality , Child , Child, Preschool , Genes, p53 , Humans , Infant , Inhibitor of Apoptosis Proteins , Neoplasm Proteins , Polymerase Chain Reaction , Prognosis , Proteins/genetics , Survival Rate , Survivin
10.
J Pediatr Surg ; 35(10): 1415-20, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11051140

ABSTRACT

PURPOSE: In patients with neuroblastoma (NB), minimal disease (MD) in bone marrow (BM) and peripheral blood (PB) is thought to play an important role in metastasis. The current study was designed to evaluate the clinical implications of the detection of MD in NB at the initial diagnosis. METHODS: Expression of the neuroendocrine protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH) mRNA in BM and PB obtained from 18 patients with NB was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: MD was detected in the BM obtained from 4 of 14 localized NB patients and also in the PB from 2. However, it was found also in both the BM and PB obtained from all 4 patients with metastatic NB. Two of the 4 MD-positive patients with localized NB had metastatic recurrence after a complete tumor excision. They also had unfavorable biological prognostic factors compared with the other 2 who did not have recurrent disease. CONCLUSION: MD detected by RT-PCR in the BM and the PB of patients with NB thus suggests a risk for metastatic disease, which in association with other unfavorable biological features may indicate a poor prognosis.


Subject(s)
Bone Marrow/pathology , Neoplastic Cells, Circulating , Nerve Tissue Proteins/genetics , Neuroblastoma/blood , Neuroblastoma/pathology , Thiolester Hydrolases/genetics , Tyrosine 3-Monooxygenase/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/metabolism , Child , Flow Cytometry , Gene Expression , Humans , Immunohistochemistry , Neoplasm Staging , Neoplasm, Residual/blood , Neoplasm, Residual/diagnosis , Neoplastic Cells, Circulating/metabolism , Neoplastic Cells, Circulating/pathology , Nerve Tissue Proteins/metabolism , Ploidies , Prognosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Thiolester Hydrolases/metabolism , Tumor Cells, Cultured , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin Thiolesterase
12.
J Antibiot (Tokyo) ; 53(5): 467-73, 2000 May.
Article in English | MEDLINE | ID: mdl-10908109

ABSTRACT

A potent sigma (sigma) receptor ligand was isolated from the culture broth of Streptomyces longispororuber #525. The active compound was identified to be (2R-trans)-2-butyl-5-heptylpyrrolidine by spectroscopic and chemical studies. The compound exhibited high affinity and selectivity for sigma receptors. The IC50 values toward sigma1, sigma2 and dopamine D2 receptors were 2.0, 22.7 and more than 40,000 nM, respectively. Its (2S-trans)- and (+/-)-cis-isomers, both synthesized, were also found to be high affinity sigma ligands.


Subject(s)
Pyrrolidines/metabolism , Receptors, sigma/metabolism , Streptomyces/metabolism , Animals , Fermentation , In Vitro Techniques , Ligands , Molecular Structure , Rats , Spectrum Analysis
13.
Phytochemistry ; 53(8): 1091-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10820837

ABSTRACT

Three putrescine (i.e. 1,4-butanediamine) bisamides were isolated from the leaves of Aglaia grandis. Their structures were elucidated by interpretation of spectral data.


Subject(s)
Plants, Medicinal/chemistry , Putrescine/analogs & derivatives , Putrescine/isolation & purification , Rosales/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Plant Leaves/chemistry , Putrescine/chemistry , Spectrometry, Mass, Fast Atom Bombardment
14.
J Pediatr Surg ; 35(1): 92-5, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10646782

ABSTRACT

PURPOSE: To elucidate the precise reason for the better prognosis in ganglioneuroblastoma (GNB) than in neuroblastoma (NB), the prognostic factors (age at diagnosis, stage at diagnosis, primary site, N-myc amplification, Shimada classification, and ploidy) were analyzed. METHODS: A retrospective analysis of the 57 neuroblastoma cases (20 GNB cases and 37 NB cases), that had not been detected by mass screening over the past 19 years at the authors' institute, was carried out. RESULTS: A Kaplan-Meier analysis of the 5-year survival rates were 67.2% and 35.1% in cases of GNB and NB, respectively, and these rates were significantly higher in GNB (logrank test; P = .04631). No significant differences were seen between GNB and NB regarding the rate in patients 1 year of age or older (95.0% v 78.4%; P = .1005), the rate of advanced cases (60.0% v 78.4%, P = .1406), the rate of an unfavorable histology (Shimada classification, 54.5% v 68.4%, P = .4473), or the diploid pattern rate (75.0% v 76.9%, P = .9200). However, N-myc amplification was found exclusively in NB (amplified cases per examined cases; 15/31), and all cases with N-myc amplification died. When the 5-year survival rate was evaluated in the patient without N-myc amplification between GNB and NB, no significant difference was observed (logrank test; P = .8568). CONCLUSION: The better prognosis in patients with GNB was thus thought to be exclusively related to an absence of N-myc amplification.


Subject(s)
Ganglioneuroblastoma/diagnosis , Ganglioneuroblastoma/genetics , Ganglioneuroblastoma/mortality , Gene Amplification , Genes, myc , Humans , Infant , Neuroblastoma/diagnosis , Neuroblastoma/mortality , Ploidies , Prognosis , Survival Rate
15.
J Pediatr Surg ; 34(11): 1615-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10591554

ABSTRACT

BACKGROUND/PURPOSE: The N-myc amplification status in neuroblastoma has been evaluated previously for the whole tumor by the Southern blot method. The aim of this study is to evaluate the effectiveness of the fluorescence in situ hybridization (FISH) method to analyze N-myc amplification in neuroblastoma and compare the findings with those using the Southern blot method. METHODS: In 26 neuroblastoma primary tumors and metastatic lesions, the N-myc amplification status was evaluated by both the Southern blot method and FISH method. RESULTS: Of the 22 samples with no N-myc amplification using Southern blot, no cells with N-myc amplification using FISH were present in 21 of the samples. However, one metastatic liver lesion showed 16% of the nuclei to display more than 10 copies of N-myc based on FISH analysis. In the 4 remaining samples with N-myc amplification using the Southern blot method (17 copies, 15 copies, 6 copies, and 3 copies), the rates of cells with more than 10 copies of N-myc based on a FISH analysis were 79%, 68%, 94%, and 9%, respectively. CONCLUSIONS: The FISH method can detect more accurately N-myc amplification than the Southern blot method either when the rate of cells with N-myc amplification is low or intratumor heterogeneity is present.


Subject(s)
Gene Expression Regulation, Neoplastic , Genes, myc , In Situ Hybridization, Fluorescence , Neuroblastoma/genetics , Blotting, Southern , Child, Preschool , Culture Techniques , Female , Gene Amplification , Humans , Infant , Male , Sensitivity and Specificity
16.
J Pediatr Surg ; 34(11): 1715-20, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10591578

ABSTRACT

PURPOSE: The correlation between the histological findings of the intrahepatic biliary epithelium and postoperative bile drainage in biliary atresia (BA) was investigated. METHODS: The patients with BA were classified into 2 groups, consisting of a good bile drainage group (GBD, n = 14, mean age at initial operation, 57.6+/-18.0 days) and a poor bile drainage group (PBD, n = 11, mean age at initial operation, 86.9+/-42.7 days). Liver specimens from an initial Kasai's operation were examined by immunostaining using anticytokeratin 7 (CK7) antibody and anti-MIB-1 antibody. The number of CK7-positive cells in the bile ductules was microscopically calculated within the 40-microm-thick interstitium along the limiting plate (LP), and the CK7-positive cell number per unit length of the LP was estimated. In addition, the MIB-1 index in bile ductules also was determined. RESULTS: The number of CK7-positive cells in PBD was significantly higher than that in GBD (167.6+/-45.6 v 117.8+/-32.4/ mm, P<.05). However, the MIB-1 index in biliary cells did not differ between the 2 groups. CONCLUSION: An increased number of intrahepatic bile duct epithelial cells in liver specimens at the initial operation may be a poor prognostic factor in BA and appears to depend on the duration of bile stasis rather than the degree of bile stasis.


Subject(s)
Antibodies, Monoclonal/metabolism , Bile Ducts, Intrahepatic/pathology , Biliary Atresia/pathology , Keratins/analysis , Nuclear Proteins/metabolism , Analysis of Variance , Bile Ducts, Intrahepatic/cytology , Biliary Atresia/surgery , Biomarkers/analysis , Cell Division , Culture Techniques , Epithelial Cells/pathology , Female , Humans , Immunohistochemistry , Infant , Infant, Newborn , Keratin-7 , Liver/cytology , Liver/pathology , Male , Mitotic Index , Sensitivity and Specificity
17.
Gan To Kagaku Ryoho ; 26(11): 1599-606, 1999 Oct.
Article in Japanese | MEDLINE | ID: mdl-10553417

ABSTRACT

We examined the antiangiogenic and antitumor efficacy of a newly-developed matrix metalloproteinase (MMP) inhibitor, BPHA (N-biphenyl sulfonyl-phenylalanine hydroxiamic acid). BPHA potently inhibits MMP-2, 9 and 14 but not MMP-1, 3 or 7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMP tested. Daily oral administration of BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth and liver metastasis, whereas (-)BPHA did not. These results demonstrate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential without hematotoxic effect or loss of body weight.


Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Matrix Metalloproteinase Inhibitors , Neovascularization, Pathologic/prevention & control , Animals , Carcinoma, Lewis Lung/drug therapy , Female , Humans , Melanoma, Experimental/drug therapy , Mice , Mice, Inbred C57BL , Mice, Nude
18.
Pediatr Surg Int ; 15(3-4): 210-3, 1999.
Article in English | MEDLINE | ID: mdl-10370025

ABSTRACT

The prevalence of Helicobacter pylori infection in postoperative patients with biliary atresia (BA) was investigated in relation to esophageal varices, portal-hypertensive gastropathy (PHG), and peptic ulcer disease (PUD) in 25 Japanese patients (10 boys and 15 girls) aged from 16 months to 20 years. Gastric biopsy specimens obtained during endoscopy were used for both the rapid urease test and modified Giemsa staining. The patients were classified into three groups according to liver function: 15 in group A (total bilirubin [TB] < 1.0 mg/dl), 7 in group B (1.0 /= 2.0 mg/dl). Esophageal varices were found in 19 patients (60% of group A and all patients in groups B and C) and PHG in 3 group B patients. However, no gastric or duodenal ulcers were found in any case. Only 2 patients (8%) had H. pylori colonization of the gastric mucosa. Both, however, belonged to group A, and the degree of chronic neutrophilic infiltration of the mucosal layer was as mild as that of the other patients. The prevalence of H. pylori infection and PUD in postoperative patients with BA was quite low, and a pathological relationship with the severity of liver disease could not be determined in these patients.


Subject(s)
Biliary Atresia/surgery , Helicobacter Infections/epidemiology , Helicobacter pylori , Postoperative Complications/epidemiology , Child , Esophageal and Gastric Varices/epidemiology , Female , Humans , Hypertension, Portal/epidemiology , Male , Peptic Ulcer/epidemiology , Peptic Ulcer/microbiology , Prevalence
19.
J Pediatr Surg ; 34(12): 1765-8, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10626850

ABSTRACT

PURPOSE: The aim of this study was to identify the most appropriate timing for surgery in newborns with choledochal cysts. METHODS: The clinical and histological data of 8 newborn cases of choledochal cysts (newborn group) were compared with 45 cases that were diagnosed later than the newborn period (late group). RESULTS: The mean and standard deviation of age at diagnosis was 0.4+/-0.4 months and 43.4+/-37.8 months in the newborn and late group, respectively. The age at operation was significantly earlier in the newborn group than in the late group (4.9+/-4.5 months v54.7+/-47.0 months). Although no significant difference in the time that elapsed between the operation and the onset of symptoms between the newborn and late groups (4.5+/-4.7 months v11.3+/-21.1 months), the serum bilirubin level (4.6+/-3.8 mg/dL v1.8+/-3.4 mg/dL) and the grade of liver fibrosis (2.0+/-0.8 v1.1+/-0.8) were significantly higher in the newborn group than in the late group. CONCLUSION: The newborn group should be considered as a special group of patients with different clinical course and pathology than those of the late group, which necessitate the early surgical intervention to prevent progression of liver fibrosis.


Subject(s)
Choledochal Cyst/diagnosis , Choledochal Cyst/surgery , Age Factors , Child, Preschool , Cholangiopancreatography, Endoscopic Retrograde , Choledochal Cyst/pathology , Disease Progression , Female , Humans , Infant , Infant, Newborn , Liver Cirrhosis/pathology , Male , Treatment Outcome
20.
Eur J Pediatr Surg ; 9(6): 409-12, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10661854

ABSTRACT

The occurrence of primary lung cancer is rare in childhood. The case of an 11-year-old boy with primary lung cancer is presented in this report. He had a substantial family history of cancer. His chief complaint was coughing with right chest pain. A chest radiograph showed a coin lesion in the right lower lung. A right lower lobectomy revealed a squamous cell carcinoma (stage IIIA at Japanese TNM classification). Systemic chemotherapy using cisplatin, vindesine, THP-adriamycin and cyclophosphamide was performed. Six months after surgery, a recurrent tumor occurred. An analysis of the familial cancer related genes (p53 gene and mismatch repair gene) showed no abnormality.


Subject(s)
Carcinoma, Squamous Cell/genetics , Lung Neoplasms/genetics , Age of Onset , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Child , Fatal Outcome , Genes, p53 , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Male , Microsatellite Repeats , Neoplasms/genetics
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