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1.
Br J Oral Maxillofac Surg ; 55(3): 251-255, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27876545

RESUMO

The submental island flap is useful as an alternative to microvascular free tissue transfer for the reconstruction of defects after resection of oral cancer because it is simple to harvest, reliable, and is associated with good oral function and low morbidity. However, because cancer of the oral cavity carries a risk of level I nodal metastases, the oncological safety of the flap remains controversial. Between April 2012 and September 2016, we studied patients with squamous cell carcinoma of the oral cavity who had surgical resection with submental island flap reconstruction for viability of the flap, signs of recurrence, and complications. Thirty-five patients (22 men and 13 women) were enrolled in the study and the mean (range) duration of follow-up was 23 (11-48) months. Six patients had local recurrences of their tumours, none of which was considered to be related to the flap. No flap was lost completely, but there were 10 cases of partial skin loss that healed with conservative management. There were no orocutaneous fistulas, haematomas, or marginal mandibular nerve palsies. We conclude that the submental island flap can be used safely in selected patients with level I lymph node metastases when the flap has been harvested meticulously.


Assuntos
Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Queixo , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos
2.
Leukemia ; 26(9): 2135-41, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22430638

RESUMO

Clonogenic multiple myeloma (MM) cells reportedly lacked expression of plasma cell marker CD138. It was also shown that CD19(+) clonotypic B cells can serve as MM progenitor cells in some patients. However, it is unclear whether CD138-negative clonogenic MM plasma cells are identical to clonotypic CD19(+) B cells. We found that in vitro MM colony-forming cells were enriched in CD138(-)CD19(-)CD38(++) plasma cells, while CD19(+) B cells never formed MM colonies in 16 samples examined in this study. We next used the SCID-rab model, which enables engraftment of human MM in vivo. CD138(-)CD19(-)CD38(++) plasma cells engrafted in this model rapidly propagated MM in 3 out of 9 cases, while no engraftment of CD19(+) B cells was detected. In 4 out of 9 cases, CD138(+) plasma cells propagated MM, although more slowly than CD138(-) cells. Finally, we transplanted CD19(+) B cells from 13 MM patients into NOD/SCID IL2Rγc(-/-) mice, but MM did not develop. These results suggest that at least in some MM patients CD138-negative clonogenic cells are plasma cells rather than B cells, and that MM plasma cells including CD138(-) and CD138(+) cells have the potential to propagate MM clones in vivo in the absence of CD19(+) B cells.


Assuntos
Linfócitos B/imunologia , Mieloma Múltiplo/imunologia , Plasmócitos/imunologia , Sindecana-1/metabolismo , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Transplante de Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Humanos , Imunofenotipagem , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Plasmócitos/metabolismo , Plasmócitos/patologia , Coelhos
3.
Leukemia ; 25(7): 1182-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21475253

RESUMO

Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNFα, BAFF and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-κB pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment.


Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Apoptose/fisiologia , Mieloma Múltiplo/enzimologia , Proteínas de Neoplasias/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Cromonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Morfolinas/farmacologia , Mieloma Múltiplo/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides , NF-kappa B/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Osteoclastos/efeitos dos fármacos , Osteoclastos/enzimologia , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirolimo/farmacologia , Células Estromais/efeitos dos fármacos , Células Estromais/enzimologia , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo
4.
Br J Haematol ; 127(3): 292-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15491288

RESUMO

The neuron cytoplasmic protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9.5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9.5 in myeloma cells was examined. PGP9.5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9.5 was observed in association with that of p27(Kip1), a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9.5. These results suggested that PGP9.5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors.


Assuntos
Biomarcadores Tumorais/análise , Mieloma Múltiplo/química , Ubiquitina Tiolesterase/análise , Western Blotting/métodos , Hipóxia Celular , Linhagem Celular Tumoral , Raios gama , Humanos , Imuno-Histoquímica/métodos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitina Tiolesterase/genética
5.
Leukemia ; 18(11): 1891-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15385929

RESUMO

Ethical and scientific concerns regarding the use of human fetal bones in the SCID-hu model of primary human myeloma prompted us to develop a novel system that uses rabbit bones implanted subcutaneously in unconditioned SCID mice. Immunohistochemical analysis of the implanted bone revealed that the majority of bone marrow (BM) microenvironment cells such as blood vessels, osteoclasts and osteoblasts were of rabbit origin. The implanted bones were directly injected with myeloma cells from 28 patients. Successful engraftment of unseparated BM cells from 85% of patients and CD138-selected myeloma plasma cells from 81% of patients led to the production of patients' M-protein isotypes and typical myeloma manifestations (osteolytic bone lesions and angiogenesis of rabbit origin). Myeloma cells grew exclusively in the rabbit bone, but were able to metastasize into another bone at a remote site in the same mouse. Cells from patients with extramedullary disease also grew along the outer surface of the rabbit bones. This demonstrates the ability of SCID-rab model, marked by a nonmyelomatous, nonhuman, and nonfetal microenvironment, to support the growth of CD138-expressing myeloma cells. This system can now be widely used to study the biology of myeloma and its manifestations and to develop novel therapeutic approaches for this disease.


Assuntos
Medula Óssea/patologia , Modelos Animais de Doenças , Glicoproteínas de Membrana/metabolismo , Mieloma Múltiplo/patologia , Células-Tronco Neoplásicas , Osteoclastos/citologia , Proteoglicanas/metabolismo , Animais , Feminino , Humanos , Camundongos , Camundongos SCID , Mieloma Múltiplo/metabolismo , Proteínas do Mieloma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/transplante , Coelhos , Sindecana-1 , Sindecanas
6.
Int J Cancer ; 94(4): 474-9, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11745431

RESUMO

To explore the antiproliferative effects of rhumAbHER2 on head and neck squamous carcinoma cell (HNSCC) lines and breast cancer cell lines (BCCLs) and to evaluate the combined effects with irradiation, 2 human HNSCC lines and 2 BCCLs were exposed to rhumAbHER2 with or without irradiation. The results showed that combined treatment enhanced the growth and colonization inhibitory effects of rhumAbHER2 or irradiation. Interestingly, the apoptotic cell fraction produced by irradiation disappeared on combined treatment. This disappearance was associated with repression of p53 and Bax upregulation induced by irradiation, but conservation of the upregulation of p27. Based on these results, rhumAbHER2 and irradiation may be a new strategy for treating HNSCC and breast cancers. In addition, the upregulation of cyclin-dependent kinase inhibitors by rhumAbHER2 may occur upstream of irradiation-induced p53 upregulation.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Proteínas Proto-Oncogênicas c-bcl-2 , Receptor ErbB-2/imunologia , Apoptose , Western Blotting , Neoplasias da Mama/radioterapia , Neoplasias da Mama/terapia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/terapia , Ciclo Celular , Divisão Celular/efeitos dos fármacos , Clonagem Molecular , Terapia Combinada , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Citometria de Fluxo , Genes erbB-2/genética , Genes p53/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Marcação In Situ das Extremidades Cortadas , Proteínas Proto-Oncogênicas/biossíntese , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/biossíntese , Regulação para Cima , Proteína X Associada a bcl-2
7.
Leuk Lymphoma ; 42(4): 761-74, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11697507

RESUMO

Two new human myeloma cell lines were established from pleural effusion and bone marrow malignant cells derived from a single patient, who manifested hyperammonemia associated with multiple myeloma, and these were characterized. Both lines possess t(11;14)(q13;q32) and t(8;14)(q24;q32) reciprocal translocations and overexpress cyclin D1, but not c-myc. Human myeloma lines including these new lines produced and secreted excess ammonia into culture medium more than non-myelomatous hematological cell lines. In addition, these two lines were revealed to have high surface CD7 expression correlated with relatively high mRNA expression by MP-RT-PCR. Among 8 human myeloma lines, half of them revealed significant surface expression of CD7 and a positive correlation between expression levels of protein and message. CD7 message was also detected in surface negative lines. Consequently, there may be posttranslational regulation of the CD7 molecule, whose cellular biological role in expressing cells has not been elucidated.


Assuntos
Antígenos CD7/metabolismo , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 8 , Mieloma Múltiplo/patologia , Translocação Genética , Células Tumorais Cultivadas/citologia , Adulto , Amônia/metabolismo , Células da Medula Óssea/patologia , Ciclina D1/metabolismo , Humanos , Hiperamonemia/etiologia , Hiperamonemia/patologia , Masculino , Mieloma Múltiplo/complicações , Mieloma Múltiplo/genética , Derrame Pleural Maligno/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/metabolismo
8.
Br J Haematol ; 114(3): 591-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11552984

RESUMO

Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.


Assuntos
Proteínas de Ciclo Celular/genética , Ciclina D1/metabolismo , Mieloma Múltiplo/genética , Ciclo Celular , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Ciclina D1/análise , Ciclina D1/genética , Primers do DNA , Expressão Gênica , Humanos , Imuno-Histoquímica , Mieloma Múltiplo/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação Genética , Células Tumorais Cultivadas
9.
Mol Microbiol ; 41(5): 1187-98, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11555297

RESUMO

SdiA, an Escherichia coli homologue of the quorum-sensing regulator, controls the expression of the ftsQAZ operon for cell division. Transcription of ftsQ is under the control of two promoters, upstream ftsQP2 and downstream ftsQP1, which are separated by 125 bp. SdiA activates transcription from ftsQP2 in vivo. Here, we demonstrate that SdiA facilitates the RNA polymerase binding to ftsQP2 and thereby stimulates transcription from P2. Gel shift and DNase I footprinting assays indicated that SdiA binds to the ftsQP2 promoter region between -51 and -25 with respect to the P2 promoter. Activation of ftsQP2 transcription by SdiA was observed with a mutant RNA polymerase containing a C-terminal domain (CTD)-deleted alpha-subunit (alpha 235) but not with RNA polymerase containing sigma(S) or a CTD-deleted sigma(D) (sigma(D)529). In good agreement with the transcription assay, no protection of P2 was observed with the RNA polymerase holoenzymes, E sigma(S) and E sigma(D)529. These observations together indicate that: (i) SdiA supports the RNA polymerase binding to ftsQP2; and (ii) this recruitment of RNA polymerase by SdiA depends on the presence of intact sigmaCTD. This is in contrast to the well-known mechanism of RNA polymerase recruitment by protein-protein contact between class I factors and alpha CTD. In addition to the P2 activation, SdiA inhibited RNA polymerase binding to the ftsQP1 promoter and thereby repressed transcription from P1. Gel shift assays indicate weak binding of SdiA to the P1 promoter region downstream from -13 (or +112 with respect to P2). Neither alpha CTD nor sigma CTD are required for this inhibition. Thus, the transcription repression of P1 by SdiA may result from its competition with the RNA polymerase in binding to this promoter.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Escherichia coli , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/metabolismo , Transdução de Sinais , Transativadores/metabolismo , Transcrição Gênica , Proteínas de Bactérias/genética , Sequência de Bases , Pegada de DNA , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Membrana/genética , Dados de Sequência Molecular , Mutação , Plasmídeos , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Transativadores/genética
10.
Leuk Lymphoma ; 41(3-4): 397-409, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11378553

RESUMO

To elucidate the role of PTHrP in myeloma, we examined the expression levels of PTHrP and its receptor in human myeloma cell lines and clinical specimens from 13 myeloma cases. In vitro modification of PTHrP expression and production induced by TGF-beta and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six out of seven myeloma cell lines with an inverse correlation with the expression of its receptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHrP expression and secretion into culture medium were enhanced by supplemental TGF-beta and PMA. PMA also seemed to affect PTHrP upregulation via TGF-beta activation. The fundamental role of PTHrP in bone lesions and hypercalcemia in myeloma may be important to consider even during the initial phase of the disease and particularly in the progression of bone complications with hypercalcemia.


Assuntos
Mieloma Múltiplo/genética , Proteínas/genética , Receptores de Hormônios Paratireóideos/genética , Idoso , Medula Óssea/patologia , Neoplasias da Mama/patologia , Citocinas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Proteína Relacionada ao Hormônio Paratireóideo , Proteínas/efeitos dos fármacos , Proteínas/fisiologia , RNA/efeitos dos fármacos , RNA/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo , Acetato de Tetradecanoilforbol/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Células Tumorais Cultivadas
11.
Br J Haematol ; 111(3): 835-42, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11122145

RESUMO

Recent investigations of the cytokine network surrounding myeloma cells have disclosed the importance of gp130-related cytokines including interleukin (IL)-6 for myeloma cell survival and proliferation, identification of IL-10 as a growth factor for myeloma cells, the close relationship between IL-10 and the receptors for gp130-related cytokines, and the growth enhancement effect of IL-11 and IL-7 on myeloma cells. In this study, IL-10 production was observed in three out of seven human myeloma cell lines examined and five (including three producing lines) out of 10 lines exhibited mRNA expression of IL-10. The IL-10 mRNA expression was also enhanced in approximately one third of primary specimens, whereas the IL-10 receptor (R) expression was not changed compared with that of normal component marrow controls. However, reverse transcription-polymerase chain reaction (RT-PCR) assay of various cytokines and their receptors showed no particular association with IL-10-producing myeloma lines compared with non-producing lines. Supplementing exogenous IL-10 or neutralization of the IL-10 signal by anti-IL-10 monoclonal antibody (mAb) in a culture conditions did not significantly affect myeloma cell growth regardless of expression of IL-10 or its receptor (IL-10R). However, supplement of anti-IL-10 mAb caused upregulation of certain genes such as IL-11, leukaemia inhibitory factor receptor (LIFR) and syndecan-1 in IL-10R-expressing cell lines. These findings indicate that the cytokine network surrounding myeloma cells is complicated and variable. In addition, IL-10 may modify this network and the cellular biological properties of myeloma cells rather than cell proliferation.


Assuntos
Interleucina-10/genética , Mieloma Múltiplo/imunologia , RNA Mensageiro/análise , Actinas/genética , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Antígenos CD/genética , Divisão Celular/efeitos dos fármacos , Receptor gp130 de Citocina , Citocinas/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-11/genética , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Proteoglicanas/genética , Receptores de Citocinas/genética , Receptores de Interleucina/genética , Receptores de Interleucina-10 , Receptores de OSM-LIF , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sindecana-1 , Sindecanas , Células Tumorais Cultivadas
12.
Int J Hematol ; 72(2): 216-22, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11039672

RESUMO

To clarify cellular biological varieties of myeloma cells, biological differences were analyzed between 2 human myeloma cell lines, KMS-12-PE and KMS-12-BM, derived from pleural effusion and bone marrow, respectively, of a single patient. Although both lines were considered to be derived from the same clone because both had the same chromosomal marker and immunoglobulin H rearrangement, several biological differences were noted. CD11a and CD20 were highly expressed in the KMS-12-BM line, whereas the KMS-12-PE line showed a higher expression of CD7 and CD95/Fas. Although growth was stimulated in KMS-12-BM by interleukin-6 and interferon-alpha, it was inhibited in KMS-12-PE. In addition, apoptosis inhibitors Bcl-2 and Bcl-X(L) were highly expressed in KMS-12-BM cells. Because KMS-12-PE was cultivated 2 months before KMS-12-BM, these differences might be related to their origin (pleural effusion and bone marrow) or the phases of disease progression. However, these biological differences may help clarify myeloma cell biology and lead to improvement in treatment for myeloma patients.


Assuntos
Mieloma Múltiplo/patologia , Células Tumorais Cultivadas , Antígenos de Superfície/análise , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Western Blotting , Medula Óssea , Divisão Celular/efeitos dos fármacos , Células Clonais , Etoposídeo/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Interferon gama/fisiologia , Interleucina-6/fisiologia , Japão , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Derrame Pleural , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/metabolismo
13.
Cancer Res ; 60(5): 1434-41, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10728710

RESUMO

It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-alpha, ER-beta, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated. In addition, effects on membrane Fas expression, appearance of apoptosis, and cell cycle perturbation were analyzed. It was revealed that ER-beta and corepressors were dominantly expressed in myeloma cells, and antiestrogens induced growth inhibition through apoptosis mediated by a Fas-related pathway and G1 arrest of the cell cycle in myeloma cell lines.


Assuntos
Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Mieloma Múltiplo/metabolismo , Receptores de Estrogênio/metabolismo , Antineoplásicos Hormonais/metabolismo , Primers do DNA , Antagonistas de Estrogênios/farmacologia , Antagonistas de Estrogênios/uso terapêutico , Estrogênios/metabolismo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Células Tumorais Cultivadas
14.
Int J Oncol ; 15(6): 1205-12, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10568829

RESUMO

Recently several chromosomal translocations involved in myeloma cases and myeloma cell lines; i.e., t(11;14)(q13;q32), t('8;14)(q24;q32), t(4;14)(q16.3;q32.3), t(6;14)(p25;q32), and t(14;16)(q32.3;q23), have been identified. These translocations are considered to dysregulate genes which may be concerned with myelomagenesis; i.e., PRAD1/cyclin D1, the c-myc oncogene, FGFR3 (fibroblast growth factor receptor 3), MMSET (multiple myeloma SET domain), MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4), and the c-maf oncogene, respectively. However, the cellular biological roles of these genes have not yet been elucidated in myeloma cells. Because two of the seven human myeloma cell lines which were established at Kawasaki Medical School, Okayama, Japan, KMS-11 and KMS-18, have been proven to possess t(4;14)(q16.3;q32.3), we studied the expression levels of the FGFR3 gene in these seven cell lines and 13 primary myeloma specimens. The expression levels of 12 known FGF family genes (FGF-1 to 12) and 4 FGFR genes (FGFR1 to 4) were also examined in seven cell lines. In addition, the growth status of the KMS-11 and KMS-18 lines with FGF-1 or anti-FGF-4 neutralizing monoclonal antibody (MoAb) supplementation was investigated because FGF-1 and 4 are known as the principal ligands for FGFR3. FGFR3 overexpression was observed in both of the cell lines possessing t(4;14)(q16.3;q32.3) and in 3 of 13 case specimens. Anti-FGF-4 neutralizing MoAb caused significant growth inhibition in these two cell lines possessing t(4;14)(q16.3;q32.3). These findings indicate that t(4;14) (q16. 3;q32.3) may provide myeloma cells with a growth advantage via an autocrine mechanism between FGFR3 and FGF-4.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 4/genética , Fatores de Crescimento de Fibroblastos/genética , Mieloma Múltiplo/genética , Proteínas Tirosina Quinases , Receptores de Fatores de Crescimento de Fibroblastos/genética , Idoso , Anticorpos Monoclonais/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Transformada , DNA Complementar/genética , Feminino , Fator 1 de Crescimento de Fibroblastos , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/imunologia , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/imunologia , Regulação Neoplásica da Expressão Gênica , Células HL-60 , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Isoformas de Proteínas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação Genética , Células Tumorais Cultivadas
15.
Kansenshogaku Zasshi ; 73(10): 1074-7, 1999 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-10565125

RESUMO

A 54-year-old male was admitted to Kawasaki Medical School Hospital with the complaint of fever. His diagnosis of hypoplastic leukemia had been made one year ago. After the admission, cecal mass with pain and high fever were noted. Four days later, he suddenly lost consciousness and died. Aeromonas hydrophila was isolated from blood cultures and also from the myofascitis specimen. Autopsy specimen of the iliopsoas muscle showed necrotizing myofascitis. The specimen obtained from the cecum showed submucosal hemorrhage with edema and these findings were compatible to ischemic colitis. This pathogen is widely distributed in nature, especially in water fields. Therefore, it would be advised to consider the Aeromonas hydrophila as one of the pathological organisms pathognomonic for the septicemia, when one may see febrile and gastrointestinal symptoms in a patient with hematological malignancies.


Assuntos
Aeromonas hydrophila , Bacteriemia/etiologia , Colite Isquêmica/etiologia , Fasciite Necrosante/etiologia , Infecções por Bactérias Gram-Negativas/etiologia , Leucemia Mieloide Aguda/complicações , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade
16.
Rinsho Ketsueki ; 40(7): 587-92, 1999 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-10483143

RESUMO

Primary splenic lymphoma (PSL) is extremely rare, accounting for less than 1% of all reported cases of extranodal lymphoma. A 62-year-old woman was referred to our hospital because of general fatigue. A heterogenous mass with irregular margins was detected in the spleen by abdominal computed tomographic scan, and Gallium scintigraphy demonstrated abnormal accumulation only in the spleen. Malignant lymphoma was strongly suspected on the basis of histologic findings from an ultrasonically guided needle biopsy. The final diagnosis was established by splenectomy as PSL of diffuse large B-cell type. After 6 courses of CHOP chemotherapy, the patient recovered and has been disease-free more than a year. Chromosomal analysis of her tumor cells detected t(3;14)(q27;q32), an abnormality not reported in cases of PSL to date. The rearrangement of BCL-6 was also observed. We discuss the possibility of BCL-6 involvement in Japanese cases of PSL, with reference to case reports dating back over the past decade.


Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 3 , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Linfoma de Células B/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Esplênicas/genética , Fatores de Transcrição/genética , Translocação Genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6
17.
Rinsho Ketsueki ; 40(7): 599-605, 1999 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-10483145

RESUMO

We report on a 16-year-old boy with B cell acute lymphocytic leukemia presenting marked leukocytosis (388,000/microliter) and resistance to multidrug chemotherapy. Karyotypical analysis revealed a novel t(3;15)(q27;q2?2) chromosomal abnormality. Because 3q27 is known to be a locus of the bcl-6 gene, which is frequently involved in B cell malignancies, molecular biological analyses were performed. Although no rearrangement was detected in 5 genes including bcl-6 on 3q27 and 2 genes on 15q2, reverse transcriptase-polymerase chain reaction procedures detected relatively strong mRNA expression of the bcl-6, smrp, dvl3, and tpml genes. These results indicate that immature leukemic cells with CD10 and CD34 positivity and rearrangement of the T cell receptor beta gene may coexist with relatively mature subpopulations that are positive for CD19 and CD20 surface markers, bcl-6 expression, and rearrangement of the gene for immunoglobulin kappa.


Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 3 , Leucemia de Células B/sangue , Leucocitose/etiologia , Translocação Genética , Adolescente , Proteínas de Ligação a DNA/genética , Humanos , Leucemia de Células B/genética , Masculino , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Fatores de Transcrição/genética
18.
Nihon Hoigaku Zasshi ; 53(3): 345-9, 1999 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-10723969

RESUMO

We report a rare case of sudden death of a patient with acute pulmonary thromboembolism associated with chlorine gas poisoning. A 21-year-old man in a water-filtration plant accidentally inhaled highly concentrated chlorine gas. He was immediately brought to a hospital after exposure. On admission, the patient had clouding of consciousness, dyspnea, and deep cyanosis. Arterial blood gas values indicated severe hypoxemia; PaO2 was 35.9 mmHg and PaCO2 was 42.4 mmHg. The clinical course was uneventful and he was satisfactorily recovering. However, ten days after admission he became sick and markedly cyanotic. He lost consciousness and then he went into cardiopulmonary arrest. Despite efforts at resuscitation, he died. An autopsy revealed bilateral pulmonary thromboembolism, although he apparently did not have any risk factor for embolism. The toxicity of chlorine gas may be related to the pulmonary thromboembolism, but the mechanisms leading to his death are unclear.


Assuntos
Cloro/intoxicação , Morte Súbita/etiologia , Embolia Pulmonar/etiologia , Acidentes de Trabalho , Doença Aguda , Adulto , Autopsia , Morte Súbita/patologia , Gases , Humanos , Exposição por Inalação , Masculino , Embolia Pulmonar/patologia
19.
Nippon Ganka Gakkai Zasshi ; 101(8): 656-61, 1997 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-9284621

RESUMO

Nine eyes with severe proliferative vitreoretinopathy underwent vitrectomy and infusion of Daunorubicin to prevent reproliferation. In 5 eyes (56%) the retina was reattached. In 4 eyes redetachment occurred because of reproliferation or incomplete sealing of the break. After a second vitrectomy, complete reattachment of the retina was obtained eventually in all eyes including one eye with silicone oil tamponade. As postoperative complications, conjunctival dehiscience occurred in 3 eyes. In two of the 3 eyes scleral buckling occurred, and orbital cellulitis occurred in one eye. Daunorubicin seemed to be effective to suppress reproliferation, but care should be taken to avoid postoperative complications.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Daunorrubicina/uso terapêutico , Vitreorretinopatia Proliferativa/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Vitrectomia , Vitreorretinopatia Proliferativa/cirurgia
20.
Chem Pharm Bull (Tokyo) ; 45(2): 327-32, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9118447

RESUMO

Griseofulvin derivatives, dl-6'-demethyl-6'-ethylgriseofulvin (dl-5) and dl-6'demethyl-6'phenylgriseofulvin (dl-6) were prepared by application of a synthetic method developed by us. Antifungal activity of these derivatives decreased in the order of dl-griseofulvin (dl-1) >> dl-6(inactive). The reaction of these derivatives with ethanethiol gave two types of compounds, 2'-(ethylthio)griseofulvin (15) and 4'-(ethylthio)isogriseofulvin (16). The relationship between the ratios of isolated yield of 15 and 16 and antifungal the activity of griseofulvin derivatives is discussed.


Assuntos
Antifúngicos/síntese química , Griseofulvina/análogos & derivados , Antifúngicos/farmacologia , Griseofulvina/síntese química , Griseofulvina/química , Griseofulvina/farmacologia , Testes de Sensibilidade Microbiana , Trichophyton/efeitos dos fármacos
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