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M Hisaoka

Publications and source records attributed to M Hisaoka.

At least 37 records · Page 2Linked to original sources
PubMed1999

Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues.

The reciprocal translocation t(17;22)(q22;q13) and a supernumerary ring chromosome, r(17;22), derived from the translocation, have been shown to be highly characteristic of dermatofibrosarcoma protuberans (DFSP). Its consequence is a fusion of two genes, a collagen type I alpha 1 gene (COL1A1) and platelet-derived growth factor B-chain gene (PDGFB). The COL1A1-PDGFB fusion gene, is expected to be a diagnostic molecular assay. However, previous studies on this subject were mostly based on frozen tissue specimens or cultured tumor cells. In this present study, the investigators conducted a reverse transcription (RT)-polymerase chain reaction (PCR) assay to detect the COL1A1-PDGFB fusion transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from 12 patients with DFSP. To amplify the fusion transcripts, a specific COL1A1 forward and PDGFB reverse primers were designed for single step PCR. The COL1A1-PDGFB fusion transcripts could be detected in 10 of 12 paraffin-embedded DFSP tumor specimens (83%). Subsequent sequence analysis using the PCR products confirmed that the detected messages were derived from gene fusions composed of PDGFB exon 2 and different regions of the COL1A1 gene (exon 8, 10, 22, 24, 32, 38, 45 or 46). Two samples of Bednar tumor included in this series also contained the fusion transcripts. In sample of DFSP with fibrosarcomatous transformation, the COL1A1-PDGFB could not be detected in the fibrosarcoma areas of the third recurrence, though the chimeric transcripts were identified in the ordinary DFSP areas of the first recurrence. No fusion transcripts could be amplified in non-DFSP lesions, including 10 dermatofibromas and 9 malignant fibrous histiocytomas. These results indicate that this molecular assay could be applied to archival formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for DFSP.

Adolescent↗
PubMed1999

Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction: application to archival paraffin-embedded tumor tissues.

Chromosomal translocations generating unique chimeric genes are highly characteristic of specific sarcomas, and their use as diagnostic markers has been suggested. From a diagnostic pathologic point of view, detection of such cytogenetic or molecular aberrations applicable to routinely processed archival tissue specimens is considered a powerful tool for tumor diagnosis. To assess the feasibility and reliability of the molecular detection of the transcript originating from the chimeric gene in paraffin-embedded tumor specimens, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the EWS-FLI1 chimeric message in a series of Ewing family tumors. Of 24 paraffin-embedded tumor specimens from 23 cases analyzed, the chimeric message was detectable in 20 (83%) specimens from 20 cases (87%) by this nested RT-PCR assay, whereas none of 7 small round cell tumors not from this family (3 alveolar rhabdomyosarcomas, 2 neuroblastomas, 2 malignant lymphomas) showed detectable chimeric messages. In the sequence analysis of the PCR products, the amplified chimeric messages contained the junctions between exon 7 of the EWS gene and any one of exons 5, 6 and 8 of the FLI1 gene. The detection process was usually completed within 3 days, except for the subseqent sequence analysis. Our results endorse the use of this molecular assay as an ancillary technique in the diagnosis of Ewing family tumors using paraffin-embedded material.

Adolescent↗
PubMed1998

Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.

Fibrosarcomatous (FS) change in a rare, but well-known phenomenon encountered in dermatofibrosarcoma protuberans (DFSP), and an increased chance in an adverse outcome has been suggested in patients with DFSP having FS areas (DFSP-FS). As altered p53 pathway has been suggested as having a potential role in tumour progression, we analysed the p53 gene and p53 protein together with the p53-related protein mdm2 and p21Waf1 in 5 cases of DFSP-FS and 13 of DFSP to ascertain whether the p53 pathway correlates to the fibrosarcomatous transformation of DFSP. Three of the five DFSP-FSs overexpressed p53 protein immunohistochemically, and one of them had a "missense" mutation of the p53 gene without immunohistochemical overexpression of mdm2 or p21Waf1. The other two DFSP-FSs with p53 overexpression demonstrated increased labelling indices of both mdm2 and p21Waf1. The three DFSP-FS patients with overexpression of p53 protein had frequent local recurrences, ranging from 3 to 5 in number with increasingly short intervals (mean 4.5 years), while one of the other two had no recurrences and the other, only one. None of the 13 DFSPs showed any alterations in the p53 gene or overexpressions of p53, mdm2 and p21Waf1, except for one DFSP having a "silent" mutation of the p53 gene. Three DFSPs had local recurrences once or twice with longer intervals to recurrence (mean 10.3 years). Although the number of cases examined is limited, the results suggest that alterations in the p53 pathway, such as overexpression of p53 protein by a mutated gene and mdm2 overexpression, are involved in fibrosarcomatous transformation in a subset of fibrohistiocytic tumours and possibly correlated with its more locally aggressive behaviour than that without p53 alterations or ordinary DFSP.

Adolescent↗
PubMed1998

Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(X;18)(p11;q11) is known to be highly characteristic of synovial sarcoma, and its consequence, an SYT-SSX fusion gene, is expected to be a diagnostic molecular marker. In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites. The SYT-SSX fusion transcripts could be detected in 30 of 32 paraffin-embedded specimens (94%). A subsequent sequence analysis using the polymerase chain reaction products confirmed that the detected messages were derived from either the SYT-SSX1 (22 cases) or SYT-SSX2 (8 cases) fusion gene. Of 23 SYT-SSX-positive monophasic tumors, 16 tumors had an SYT-SSX1 fusion transcript. Fusion transcripts were detectable in all the 7 biphasic tumors analysed, one of which had an SYT-SSX2 fusion transcript. All of the six tumors at unusual locations (lung; 3, metastasis to the abdominal cavity from a tumor of retroperitoneal origin; 1, sacral region; 1, iliopsoas muscle; 1) contained detectable messages. Our results indicate that this molecular assay can be applied to archival formalin-fixed, paraffin-embedded tumor tissues as a feasible and reliable molecular technique for the diagnosis of synovial sarcoma.

Adolescent↗
PubMed1998

Peripheral primitive neuroectodermal tumour of the lung: report of two cases.

AIMS: We report two unusual cases of intrapulmonary small round cell tumour with evidence that they are primitive neuroectodermal tumours. METHODS AND RESULTS: The patients were a 25-year-old woman and a 15-year-old man, in whom mass shadows were found by routine chest radiography. Both tumours were located in the pulmonary parenchyma, and there was no evidence of an extrapulmonary involvement by the tumour. The lesions showed morphological and immunophenotypic features consistent with peripheral primitive neuroectodermal tumour (pPNET). These features included a hypercellular diffuse growth pattern of closely packed small round cells occasionally forming abortive Homer-Wright-type rosettes and intense immuroreactivities to neurone-specific enolase and MIC2 gene product (O13). Unusual chondroid foci were present in one of the cases. This diagnosis was further supported by the cytogenetic and reverse transcriptase-polymerase chain reaction (RT-PCR) findings of the characteristic t(11;22) chromosomal translocation and EWS/FLI-1 fusion transcripts, respectively, in one of the cases. CONCLUSIONS: These morphological and cytogenetic findings substantiate pPNET as a subtype of intrapulmonary small round cell tumours.

Adolescent↗
PubMed1998

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

Adolescent↗
PubMed1998

Intranodal palisaded myofibroblastoma with so-called amianthoid fibers: a report of two cases with a review of the literature.

Two cases of intranodal myofibroblastoma, a rare primary spindle cell tumor of the lymph node, are described. The tumors arose in the inguinal or proximal region of the thigh of one middle-aged and one elderly Japanese male. The tumors were well-demarcated and composed of a fascicular proliferation of spindle cells with focal nuclear palisading and acellular stellate-shaped collagen-rich areas (so-called amianthoid fibers), and were associated with hemorrhagic areas. Immunohistochemically, the tumor cells were positive for vimentin and muscle actin. Together with ultrastructural findings of intracytoplasmic microfilaments with focal densities and profiles of well-developed, rough endoplasmic reticulum, these features reinforced the conclusion of myofibroblastic or smooth muscle differentiation of the tumor cells. One of the tumors was analyzed by flow cytometry and was shown to be DNA diploid. The present report provides clinicopathological findings of the first two Japanese cases of intranodal myofibroblastoma.

Actins↗
PubMed1998

Species variation in pharmacokinetics and opsonization of palmitoyl rhizoxin (RS-1541) incorporated in lipid emulsions.

Highly lipophilic antitumor agent, palmitoyl rhizoxin (RS-1541), was incorporated into stable lipid emulsions about 100-1000nm in mean diameter consisting of triglyceride ODO and surfactant HCO-60. The pharmacokinetics of RS-1541 were studied after i.v. injection in mice, rats, rabbits, and dogs. Dog showed characteristic pharmacokinetics of RS-1541, compared with other species. RS-1541 was much more rapidly eliminated from plasma with emulsion particles in dogs than in mice, rats, and rabbits. Most amounts of injected RS-1541 were recovered in the liver six hours after administration to dogs, while less than 20% recoveries were observed for mice and rats. To clarify this species variation, opsonization of emulsion particles were evaluated. When emulsions (about 200nm in size) were opsonized by dog plasma, and intravenously injected to rats, total clearance and liver uptake of RS-1541 were increased to 1.8 fold and 2.7 fold of control values, respectively. In contrasts, emulsions opsonized by mouse, rabbit and human plasma did not show such drastic changes in pharmacokinetics of RS-1541 in rats. Furthermore, total clearance of RS-1541 for emulsions opsonized by dog plasma was increased to 1.9 fold of controls after injection to rabbits. These results indicate that opsonizing activities of dog plasma for RS-1541 emulsions are high, compared with other species. This species variation in opsonizing process probably caused the species variation in the pharmacokinetics of RS-1541 incorporated in lipid emulsions.

Animals↗
PubMed1998

Diagnostic implication of Kaposi's sarcoma-associated herpesvirus with special reference to the distinction between spindle cell hemangioendothelioma and Kaposi's sarcoma.

OBJECTIVE: To assess the diagnostic utility of recently identified Kaposi's sarcoma-associated herpesvirus (KSHV, also referred to as human herpesvirus 8) in distinction between Kaposi's sarcoma (KS) and other types of vascular lesion, especially spindle cell hemangioendothelioma (SCH). DESIGN: We conducted a polymerase chain reaction analysis of KSHV in 93 cases of benign and malignant vascular lesions, using DNA extracted from archival specimens. RESULTS: All five cases of Kaposi's sarcoma examined, including cases related and cases unrelated to acquired immunodeficiency syndrome, were positive for KSHV. Vascular lesions other than KS, including 6 SCH, 1 kaposiform hemangioendothelioma, 8 angiosarcomas, 46 hemangiomas (15 cavernous, 12 capillary, 7 venous, 6 intramuscular, 2 sinusoidal, 2 epithelioid, 1 microvenular, 1 glomeruloid), and 7 glomus tumors were consistently negative, except for 1 of the 20 pyogenic granulomas examined. CONCLUSIONS: Our data support the previous finding that KSHV is confined almost exclusively to KS, irrespective of human immunodeficiency virus infection, and suggest that KSHV is a reliable diagnostic marker to differentiate KS from other vascular lesions, including those with KS-like morphology, such as SCH.

Base Sequence↗
PubMed1998

Dermatofibrosarcoma protuberans and its fibrosarcomatous variant with areas of myoid differentiation: a report of three cases.

AIMS: We describe three examples of dermatofibrosarcoma protuberans which demonstrated focal myofibroblastic differentiation, and discuss the nature of myofibroblastic differentiation. METHODS AND RESULTS: We studied three cases of dermatofibrosarcoma protuberans, two of which had fibrosarcomatous portions containing myoid areas, and one which showed myoid areas in ordinary dermatofibrosarcoma protuberans. Myoid areas were recognized histologically as randomly distributed, scattered bundles or small nodules of spindle cells with deeply eosinophilic cytoplasm. Myofibroblastic differentiation was demonstrated immunohistochemically by positive staining for smooth muscle actin and muscle-specific actin, and ultrastructurally by the presence of microfilament bundles with focal dense bodies and pinocytic vesicles. The myoid areas occasionally contained intraneoplastic blood vessels. CONCLUSION: The presence of myoid areas may be related to reactive hyperplasia of stroma, and its relation to the histogenesis of dermatofibrosarcoma protuberans is uncertain.

Actins↗
PubMed1997

Interphase cytogenetic analysis of myxoid soft tissue tumors by fluorescence in situ hybridization and DNA flow cytometry using paraffin-embedded tissue.

BACKGROUND: Myxoid liposarcoma is one of the major myxoid malignancies of soft tissue and its histologic differentiation from other myxoid tumors is sometimes difficult. Recent cytogenetic analysis revealed that a characteristic reciprocal chromosomal translocation of t(12;16)(q13;p11) occurs in myxoid liposarcomas. In this study, retrospective cytogenetic analysis by means of fluorescence in situ hybridization (FISH) and DNA flow cytometry were performed on free nuclei isolated from paraffin embedded myxoid liposarcoma cells, and they were compared with myxoid malignant fibrous histiocytomas (MFHs), low grade fibromyxoid sarcomas, and intramuscular myxomas. METHODS: Nine myxoid liposarcomas, five myxoid MFHs, two low grade fibromyxoid sarcomas, and four intramuscular myxomas were examined. Chromosomal aberrations in chromosomes 12 and 16 were investigated by FISH, using both centromeric DNA probes and whole chromosome painting probes. Cellular DNA contents were determined by flow cytometry. RESULTS: All nine myxoid liposarcomas were shown to be diploid by DNA flow cytometry and exhibited the translocation t(12; 16), as shown by FISH. Four of the five myxoid MFHs exhibited aneuploidy, as shown by flow cytometry, and remarkable numeric aberrations of chromosomes 12 and 16. No abnormal DNA content or chromosomal aberrations were identified in the two low grade fibromyxoid sarcomas or the four intramuscular myxomas. CONCLUSIONS: FISH analysis performed on paraffin embedded materials can be used to differentiate myxoid liposarcomas from other myxoid soft tissue tumors.

Adult↗
PubMed1997

Maffucci's syndrome associated with spindle cell hemangioendothelioma.

The case of a 49-year-old man with Maffucci's syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.

Angiography, Digital Subtraction↗
PubMed1997

Peripheral primitive neuroectodermal tumour with ganglioneuroma-like areas arising in the cauda equina.

Peripheral primitive neuroectodermal tumour (pPNET or peripheral neuroepithelioma) is one of the malignant small round cell tumours of peripheral nerves, soft tissues and bones, but rarely originates in the spinal canal. We report an example of pPNET arising in the cauda equina of a 14-year-old Japanese boy. At surgery, a well-demarcated tumour measuring 2 x 4 cm in diameter and involving one of the nerve roots of the cauda equina was located within the intradural space with no evidence of extradural extension. Microscopically the tumour was made up of sheets of closely packed small round cells, associated with ganglioneuroma-like islands. Immunohistochemically, the small round tumour cells were intensely positive for neuron-specific enolase (NSE), an MIC2 gene product (O13) and beta 2-microglobulin, whereas the foci with ganglion cell-like cells reacted positively to NSE, synaptophysin and beta 2-microglobulin but were negative for O13. A chimeric transcript of the EWS/FLI-1 fusion gene detected by a nested reverse transcriptase-polymerase chain reaction using formalin-fixed paraffin-embedded tissue justified the diagnosis of pPNET. Only 6 cases of PNET in the cauda equina have been described in the literature, and this is the first case of a pPNET with ganglio-neuroma-like areas. This finding suggests that the primitive tumour cells of pPNET may respond to unknown inductive effects and express a ganglion cell-like morphology.

Adolescent↗
PubMed1997

Clinicopathological and interphase cytogenetic analysis of desmoid tumours.

AIMS: Recurrence of desmoid tumours is difficult to predict from only histological findings. In this study, immunohistochemistry for counting stromal blood vessels and proliferative activity, DNA flow cytometry, and interphase cytogenetic analysis of chromosome 8 by fluorescence in-situ hybridization (FISH) were performed to assess the correlation between their parameters and the recurrence of desmoid tumours. METHODS AND RESULTS: The cases examined included 16 extra-abdominal desmoid and eight abdominal desmoids, comprising 14 recurrent and 10 non-recurrent cases. Eleven (69%) of the 16 extra-abdominal desmoids and three (38%) of the eight abdominal desmoids recurred. Patients with recurrent lesions (mean age, 20 years) were younger than those with non-recurrent tumours (34 years). Histologically, tumours with hypervascular areas frequently recurred after surgery in comparison with those with hypovascularity. There was no significant correlation between tumour size, the labelling index of the proliferating cell nuclear antigen (PCNA) and the recurrence. In flow cytometric analysis, all the cases examined showed a diploid pattern. The FISH study revealed that the incidence of trisomy 8 was significantly higher in the recurrent (72.7%) than in the non-recurrent cases (12.5%). CONCLUSIONS: These results suggest that a subgroup of desmoid tumours at risk of recurrence may be hypervascular lesions associated with trisomy 8.

Adolescent↗
PubMed1997

Dedifferentiated liposarcoma with an inflammatory malignant fibrous histiocytoma-like component presenting a leukemoid reaction.

A rare case of dedifferentiated liposarcoma (well-differentiated liposarcoma with an inflammatory malignant fibrous histiocytoma (MFH)-like anaplastic component) occurring in a 69-year-old male is presented. The patient had noticed a dull pain in his left loin and thigh for about 1 month. Computed tomography examination revealed a low-density mass lesion, measuring about 6 cm in diameter, in the left iliopsoas muscle, and it was surgically removed. Grossly, the lesion was composed of an encapsulated, soft, whitish mass and an adjacent, well-demarcated, yellowish hard nodule, measuring about 2.5 cm in diameter. Microscopically, both lesions showed features of an inflammatory variant of MFH and a sclerosing type of well-differentiated liposarcoma, respectively. To our knowledge, only two cases of dedifferentiated liposarcoma combined with inflammatory MFH as a dedifferentiated component have been recorded in the literature. The salient feature of the present case is a systemic inflammatory reaction, as shown by prominent leukocytosis (up to 73,900/mm3) and the elevated serum value of C reactive protein (up to 26.0 mg/dL), which were transiently reduced after surgery. The inflammatory reaction was suggested to be induced by cytokines, such as granulocyte colony-stimulating factor and interleukin-6, which were probably produced by the tumor cells in the present case, because the elevated serum values of those cytokines were decreased after surgery.

Aged↗
PubMed1997

Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers.

CS-834, (+)-[pivaloyloxymethyl (4R,5S,6S)-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(R)-5-oxopyrroli din-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate], is an ester-type oral carbapenem prodrug, and an active metabolite is R-95867, which has antibacterial activity. CS-834 was administered orally to healthy male volunteers at single doses of 50, 100, 200, and 400 mg and at a multiple dose of 150 mg three times a day for 7 days to investigate its safety and pharmacokinetic profiles. Other studies were conducted to examine the effect of food intake on the bioavailability of CS-834 and also the effect of the coadministration of probenecid on the pharmacokinetics of CS-834. In the fasting state, the concentration of R-95867 in plasma reached maximum levels from 1.1 to 1.7 h after the oral administration of CS-834, followed by a monoexponential decrease. The maximum concentrations of R-95867 in serum (C[max]s) after the administration of CS-834 at doses of 50, 100, 200, and 400 mg were 0.51, 0.97, 1.59, and 2.51 microg/ml, respectively. The half-lives (t1/2s) were almost constant, approximately 0.7 h. The areas under the concentration-time curves (AUCs) were proportional to the doses, ranging from 50 to 400 mg x h/ml. The cumulative recoveries in urine were approximately 30 to 35% until 24 h after drug administration. The C(max), AUC, t1/2, and recovery in urine were not affected by food intake. Probenecid coadministration prolonged the t1/2, and it increased the C(max) and AUC for R-95867 by approximately 1.5- and 2.1-fold, respectively. The multiple-dose study showed no change in the pharmacokinetics from those for the single doses and no drug accumulation in the body. A mild transient soft stool was observed in one volunteer in the study with a single dose of 400 mg. In the multiple-dose study, mild transient soft stools were observed in six volunteers, one volunteer had mild transient diarrhea, and one volunteer had elevated serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase levels (1.4- and 2.8-fold compared with the upper limits of normal, respectively). There were no other abnormal findings for objective symptoms or laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis.

Administration, Oral↗
PubMed1997

Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834.

We have studied an ester prodrug of a carbapenem to develop a potent orally active beta-lactam antibiotic. A variety of 1 beta-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[(R)-5-oxopyrrolidin-3-yl thio]- l-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.

Administration, Oral↗