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1.
Acta Virol ; 62(2): 147-156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895155

RESUMO

High-risk human papillomaviruses (HPVs) possess transforming activity leading to development of the cancer, including oropharyngeal, anal, penile, vulvar, vaginal, and cervical cancer. The stability of E6 is essential for its complete function as an oncoprotein. Using the yeast two-hybrid system, we identified ubiquitin-specific protease 15 (USP15) as an HPV16 E6-interacting protein. USP15 cleaves polyubiquitin chains of HPV16 E6 and/or ubiquitin precursors. Our results indicate that USP15 could increase the level of HPV16 E6 by inhibiting E6 degradation. USP15 inhibited the degradation of HPV16 E6 in dose-dependent manner. In contrast, catalytically inactive mutants of USP15 had a reduced inhibitory effect on E6 degradation. In particular, USP15 mutants of all three cysteine boxes and the NHL mutant of the KRF box had a drastically reduced inhibitory effect on HPV16 E6 degradation. In addition, HPV16 E6 mRNA was not induced by USP15; therefore, HPV16 E6 appears to be post-translationally regulated. These results suggest that USP15 has the ability to stabilize E6 as a deubiquitinating enzyme, and as an oncoprotein affects biological functions in infected human cells.


Assuntos
Papillomavirus Humano 16/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/enzimologia , Proteínas Repressoras/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Domínio Catalítico , Interações Hospedeiro-Patógeno , Papillomavirus Humano 16/genética , Humanos , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Ligação Proteica , Proteólise , Proteínas Repressoras/genética , Técnicas do Sistema de Duplo-Híbrido , Proteases Específicas de Ubiquitina/química , Proteases Específicas de Ubiquitina/genética
3.
Minim Invasive Neurosurg ; 54(3): 142-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21863525

RESUMO

BACKGROUND: Lumbar foraminal stenosis is a troublesome disease. Decompression of the whole length of the nerve root from the spinal canal to extraforaminal zone is often a surgical requirement due to the difficulty in identifying the nerve compression site before surgery, making preservation of the posterior elements difficult. The authors report a minimally invasive microendoscopic technique for lumbar foraminal stenosis to decompress the entire length of the nerve root from the spinal canal to the extraforaminal zone while preserving the posterior elements. SURGICAL PROCEDURE: A tubular retractor is inserted towards the base of the transverse process of the upper vertebra with the retractor tilted inward at a 45-degree angle or greater. Approximately one-third of the pedicle is resected caudally from the base of the transverse process to the spinal canal. After identification of the nerve root, compression factors around the nerve are excised from the spinal canal to the extraforaminal zone without damaging posterior elements such as the facet joints and pars interarticularis. RESULTS: We treated 6 patients with lumbar foraminal stenosis using this procedure. There were no complications during the operation, and satisfactory results were obtained in all cases. CONCLUSIONS: This microendoscopic technique proved to be useful for the treatment of lumbar foraminal stenosis.


Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuroendoscopia/métodos , Radiculopatia/cirurgia , Estenose Espinal/cirurgia , Idoso , Descompressão Cirúrgica/instrumentação , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Masculino , Microscopia/instrumentação , Microscopia/métodos , Microcirurgia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Neuroendoscopia/instrumentação , Radiculopatia/patologia , Radiculopatia/fisiopatologia , Radiografia , Estenose Espinal/patologia , Estenose Espinal/fisiopatologia
4.
Prostate ; 71(7): 778-90, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21031437

RESUMO

BACKGROUND: Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break-fusion-bridge cycle that can lead to manifestations of genomic instability. METHODS: In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress. RESULTS: We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C-MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer. CONCLUSIONS: Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer.


Assuntos
Instabilidade Genômica , Neoplasia Prostática Intraepitelial/genética , Neoplasias da Próstata/genética , Telômero , Biomarcadores Tumorais/metabolismo , Aberrações Cromossômicas , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8 , DNA de Neoplasias/análise , Humanos , Processamento de Imagem Assistida por Computador , Hibridização in Situ Fluorescente , Antígeno Ki-67/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Prostatectomia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
5.
Braz. j. med. biol. res ; 43(8): 799-805, Aug. 2010. tab, ilus
Artigo em Inglês | LILACS | ID: lil-554954

RESUMO

Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH) in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.


Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Aberrações Cromossômicas , DNA , Endometriose/genética , Doenças Ovarianas/genética , Endometriose/patologia , Perda de Heterozigosidade , Hibridização de Ácido Nucleico/genética , Doenças Ovarianas/patologia , Reação em Cadeia da Polimerase
6.
Cytogenet Genome Res ; 128(4): 199-213, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20453501

RESUMO

It has been proposed that regions of microhomology in the human genome could facilitate genomic rearrangements, copy number transitions, and rapid genomic change during tumor progression. To investigate this idea, this study examines the role of repetitive sequence elements, and corresponding syntenic mouse genomic features, in targeting cancer-associated genomic instability of specific regions of the human genome. Automated database-mining algorithms designed to search for frequent copy number transitions and genomic breakpoints were applied to 2 publicly-available online databases and revealed that 6p21-p12 is one of the regions of the human genome most frequently involved in tumor-specific alterations. In these analyses, 6p21-p12 exhibited the highest frequency of genomic amplification in osteosarcomas. Analysis of repetitive elements in regions of homology between human chromosome 6p and the syntenic regions of the mouse genome revealed a strong association between the location of segmental duplications greater than 5 kilobase-pairs and the position of discontinuities at the end of the syntenic region. The presence of clusters of segmental duplications flanking these syntenic regions also correlated with a high frequency of amplification and genomic alteration. Collectively, the experimental findings, in silico analyses, and comparative genomic studies presented here suggest that segmental duplications may facilitate cancer-associated copy number transitions and rearrangements at chromosome 6p21-p12. This process may involve homology-dependent DNA recombination and/or repair, which may also contribute towards the overall plasticity of the human genome.


Assuntos
Cromossomos Humanos Par 6 , Genoma , Neoplasias/genética , Duplicações Segmentares Genômicas/genética , Sintenia , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Diferenciação Celular , Aberrações Cromossômicas/classificação , Mapeamento Cromossômico , Amplificação de Genes , Rearranjo Gênico , Humanos , Camundongos , Neoplasias/patologia , Hibridização de Ácido Nucleico , Osteoblastos/citologia , Osteossarcoma/genética , Osteossarcoma/patologia , Recidiva , Elementos Nucleotídeos Curtos e Dispersos/genética
7.
Cytogenet Genome Res ; 122(1): 5-15, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18931480

RESUMO

Osteosarcoma (OS) is characterized by an unstable karyotype which typically has a heterogeneous pattern of complex chromosomal abnormalities. High-resolution array comparative genomic hybridization (CGH) in combination with interphase fluorescence in situ hybridization (FISH) analyses provides a complete description of genomic imbalances together with an evaluation of the contribution of cell-to-cell variation to copy number changes. There have been no analyses to date documenting genomic signatures consistent with chromosomal instability mechanisms in OS tumors using array CGH. In this study, we utilized high-resolution array CGH to identify and characterize recurrent signatures of genomic imbalances using ten OS tumors. Comparison between the genomic profiles identified tumor groups with low, intermediate and high levels of genomic imbalance. Bands 6p22-->p21, 8q24 and 17p12--> p11.2 were consistently involved in high copy gain or amplification events. Since these three locations have been consistently associated with OS oncogenesis, FISH probes from each cytoband were used to derive an index of cellular heterogeneity for copy number within each region. OS with the highest degree of genomic imbalance also exhibited the most extreme cell-to-cell copy number variation. Significantly, the three OS with the most imbalance and genomic copy number heterogeneity also had the poorest response to preoperative chemotherapy. This genome wide analysis is the first utilizing oligonucleotide array CGH in combination with FISH analysis to derive genomic signatures of chromosomal instability in OS tumors by studying genomic imbalance and intercellular heterogeneity. This comprehensive genomic screening approach provides important insights concerning the mechanisms responsible for generating complex genomes. The resulting phenotypic diversity can generate tumors with a propensity for an aggressive disease course. A better understanding of the underlying mechanisms leading to OS tumor development could result in the identification of prognostic markers and therapeutic targets.


Assuntos
Neoplasias Ósseas/genética , Instabilidade Cromossômica , Osteossarcoma/genética , Adolescente , Neoplasias Ósseas/patologia , Criança , Cromossomos Artificiais Bacterianos/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 8/genética , Feminino , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Interfase/genética , Cariotipagem , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/patologia , Prognóstico
8.
Eur J Surg Oncol ; 34(4): 365-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17532172

RESUMO

PURPOSE: Sentinel lymph node biopsy (SNB) has been a standard technique in early breast cancer. However, it is not clear that the SNB procedure can be applied to second breast cancer or recurrence occurring in the previously treated breast. The purpose of this study was to clarify the feasibility of the SNB procedure in breast cancer occurring in the previously treated breast, and to investigate the factors related to altered lymphatic flow. PATIENTS AND METHODS: Between April 2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among them, 31 patients had a history of previous treatments in the same breast. Recent excision biopsy cases were not included in this group. All patients had previous breast-conserving surgery in the same breast. Sixteen patients had axillary dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had received radiation therapy to the breast and axilla. Visualization of axillary nodes, internal mammary nodes and contralateral axillary nodes was evaluated and compared with pathological results. RESULTS: Axillary nodes were visualized in 23 patients, internal mammary nodes in 7 patients, and contralateral axillary nodes in 7 patients. The patients with previous axillary dissection exhibited altered lymph node distribution, but did not show involvement of contralateral axillary nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10 patients with previous irradiation to breast irrespective of axillary dissection. Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes. Three patients were cancer-positive in non-ipsilateral axillary nodes (one patient showed positive opposite axillary node and two patients showed positive internal mammary nodes). CONCLUSION: Previous axillary dissection or irradiation to the breast greatly influences lymphatic flow. Irradiation to the breast may be a strong factor for the visualization of contralateral axillary nodes. Despite the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary or recurrent breast cancer patients.


Assuntos
Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária/patologia , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Excisão de Linfonodo , Sistema Linfático/efeitos da radiação , Sistema Linfático/cirurgia , Mastectomia Segmentar
9.
Br J Cancer ; 97(5): 678-85, 2007 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-17700571

RESUMO

This study examines the clinical impact of PTEN genomic deletions using fluorescence in situ hybridisation (FISH) analysis of 107 prostate cancers, with follow-up information covering a period of up to 10 years. Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours. FISH analysis using closely linked probes centromeric and telomeric to the PTEN indicated that subband microdeletions accounted for approximately 70% genomic losses. Kaplan-Meier survival analysis of PTEN genomic losses (hemizygous and homozygous deletion vs not deleted) identified subgroups with different prognosis based on their time to biochemical relapse after surgery, and demonstrated significant association between PTEN deletion and an earlier onset of disease recurrence (as determined by prostate-specific antigen levels). Homozygous PTEN deletion was associated with a much earlier onset of biochemical recurrence (P=0.002). Furthermore, PTEN loss at the time of prostatectomy correlated with clinical parameters of more advanced disease, such as extraprostatic extension and seminal vesicle invasion. Collectively, our data indicates that haploinsufficiency or PTEN genomic loss is an indicator of more advanced disease at surgery, and is predictive of a shorter time to biochemical recurrence of disease.


Assuntos
Deleção Cromossômica , Hibridização in Situ Fluorescente/métodos , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/patologia , Idoso , Cromossomos Humanos Par 10 , Deleção de Genes , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética
10.
Eur J Surg Oncol ; 32(7): 738-42, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16806793

RESUMO

AIMS: Methods of administering (99m)Tc-phytate during sentinel node biopsy of early breast cancer patients were compared to improve the sensitivity of the technique. METHODS: Two injection methods, intradermal vs. intradermal-plus-deep injection, were compared in 648 early breast cancer patients. Intradermal injection was done in 323 consecutive patients (325 breasts), and intradermal-plus-deep injection was done in 325 consecutive patients (329 breasts). The following items were compared: (1) The number of axillary nodes detected scintigraphically and removed surgically, and the breast number of micrometastasis to axillary nodes; (2) The number of internal mammary nodes detected scintigraphically and removed surgically; and (3) The sensitivity of axillary SNB. RESULTS: The number of axillary nodes scintigraphically detected was 1.63+/-0.80 (mean+/-SD) in patients given intradermal injection, and was 1.82+/-0.94 in patients given intradermal-plus-deep injection. The number of axillary nodes surgically removed was 1.78+/-0.93 in patients given intradermal injection, and was 1.95+/-0.99 in patients given intradermal-plus-deep injection. The visualization of internal mammary nodes was superior with intradermal-plus-deep injection (5/325 for intradermal, and 51/329 for intradermal-plus-deep). The putative sensitivity was 71/72 (98.6%) for the intradermal-plus-deep method and 56/62 (90.3%) for the intradermal method. The frequency of detection of micrometastasis was 24 in 71 true positive (38.8%) for the intradermal-plus-deep method and 13 in 56 true positive (23.2%) for the intradermal method. CONCLUSIONS: The SNB procedure with the intradermal-plus-deep injection method detected more axillary and internal mammary nodes, more (not statistically significant) micrometastasis and improved the putative sensitivity more than the SNB procedure with the intradermal injection method.


Assuntos
Neoplasias da Mama/patologia , Compostos de Organotecnécio/administração & dosagem , Ácido Fítico/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Biópsia de Linfonodo Sentinela , Axila , Mama , Feminino , Humanos , Injeções Intradérmicas , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/métodos
11.
Eur J Surg Oncol ; 32(10): 1101-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16626922

RESUMO

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.


Assuntos
Neoplasias da Mama/patologia , Linfonodos/efeitos da radiação , Compostos de Organotecnécio , Ácido Fítico , Compostos Radiofarmacêuticos , Rênio , Biópsia de Linfonodo Sentinela , Compostos de Tecnécio , Axila , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Doses de Radiação
12.
Eur J Surg Oncol ; 31(8): 840-4, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16009528

RESUMO

AIMS: To study the significance of lymphatic drainage disruption due to a surgical scar in sentinel node mapping (SNM) in breast cancer patients. METHODS: We reviewed patients with stage I breast cancer who had undergone SNM and had an old surgical scar in the ipsilateral breast. RESULTS: Of 534 breast cancer patients who had undergone SNM, five patients had an old scar in the ipsilateral breast. Inter-pectoral nodes, internal nodes, intramammary nodes, and contralateral axillary nodes were identified as sentinel nodes in three cases. In the remaining two cases, no sentinel lymph nodes were identified. CONCLUSIONS: An old surgical scar in the breast may cause lymphatic drainage disruption, resulting in abnormal radioactive colloid uptake during SNM.


Assuntos
Neoplasias da Mama/patologia , Cicatriz/patologia , Biópsia de Linfonodo Sentinela/métodos , Idoso , Axila , Mama , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Corantes , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Músculos Peitorais , Cintilografia , Compostos Radiofarmacêuticos
13.
Eur J Surg Oncol ; 30(10): 1077-83, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15522554

RESUMO

AIM: Large multicenter, randomized trials have revealed the advantages of using tamoxifen for 5 years vs 2 years in breast cancer patients. The aim of this report is to confirm the optimal duration of tamoxifen administration in a study of Japanese breast cancer patients. METHODS: Japanese post-menopausal estrogen receptor-positive breast cancer patients treated with mastectomy were randomly assigned to either a 5-year or 2-year course of tamoxifen. The primary endpoint was disease-free survival, with secondary endpoints of overall survival and a reduction in the development of metachronous contra-lateral breast cancer. RESULTS: A total of 256 breast cancer patients were randomized to a 5-year or 2-year tamoxifen administration group. After a median follow-up time of 81 months, there were no significant differences seen in terms of disease-free or overall survival (p=0.65 and 0.56, respectively). Furthermore, the impact of the 5-year use of tamoxifen on the development of contra-lateral breast cancer did not reach statistical significance (p=0.0511). However, 5-year tamoxifen use was closely associated with gynaecological complications (p=0.0081). CONCLUSION: We could not show a beneficial effect of using tamoxifen for 5 years over 2 years in Japanese estrogen receptor-positive patients. This is likely due to the small number of patients enrolled in our study; however, racial disparity may influence this result. A reevaluation is necessary to study the advantages of the 5-year use of tamoxifen in the Japanese racial subgroup.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Pós-Menopausa , Tamoxifeno/uso terapêutico , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Povo Asiático/etnologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Antagonistas de Estrogênios/efeitos adversos , Feminino , Seguimentos , Doenças dos Genitais Femininos/induzido quimicamente , Humanos , Japão/etnologia , Metástase Linfática/patologia , Mastectomia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/prevenção & controle , Receptores de Estrogênio/análise , Taxa de Sobrevida , Tamoxifeno/efeitos adversos
14.
Neuropathol Appl Neurobiol ; 30(5): 546-54, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15488031

RESUMO

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by the presence of neuronal and oligodendroglial alpha-synuclein aggregates. To investigate the relationship between the occurrence of neuronal cytoplasmic and intranuclear inclusions (NCIs and NNIs, respectively) and the progression of neuronal degeneration, we performed a quantitative analysis of the pontine and inferior olivary nuclei based on 14 cases of MSA. alpha-Synuclein immunohistochemistry revealed that NCIs and NNIs were present in both brain nuclei in all the cases. The average incidence of NCIs in the pontine and inferior olivary nuclei was 9.1% and 25.8%, respectively, and that of NNIs was 9.2% and 9.0%, respectively. The number of NNIs was strongly correlated with that of neurones in the pontine and inferior olivary nuclei. Although the number of NCIs was not correlated with the neuronal population in both nuclei, the NCI count in patients with moderate MSA was higher than in patients with mild MSA. The NNI count was much higher than the NCI count in the pontine nucleus in four patients, and was the same in the olivary nucleus in three of the four patients. Moreover, the neuronal population in the NNI-predominant cases was significantly higher than in the NCI-predominant cases. These findings suggest that NCI formation is accelerated by the progression of the disease process, and that in MSA, NNI formation is an earlier phenomenon than NCI formation.


Assuntos
Corpos de Inclusão/patologia , Corpos de Inclusão Intranuclear/patologia , Atrofia de Múltiplos Sistemas/patologia , Neurônios/patologia , Núcleo Olivar/patologia , Ponte/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Corpos de Inclusão/ultraestrutura , Corpos de Inclusão Intranuclear/ultraestrutura , Masculino , Microscopia Imunoeletrônica , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Núcleo Olivar/metabolismo , Ponte/metabolismo , Sinucleínas , alfa-Sinucleína
15.
Br J Cancer ; 89(9): 1627-32, 2003 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-14583760

RESUMO

Preclinical studies have demonstrated the synergistic anti-tumour activity of combination therapy with the oral cytostatics, 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA), in human breast cancer xenograft models. This study was performed to evaluate the efficacy and safety of this oral combination chemotherapy in the treatment of metastatic breast cancer. In all, 101 patients with metastatic breast cancer were enrolled in the study, and the data for 94 eligible patients of these were evaluated. The patients received twice daily oral combinations of 5'-DFUR (1200 mg/body/day) and CPA (100 mg/body/day) for 2 weeks, followed by a 1-week rest period. After a median of 19 treatment cycles (range 1-66 cycles), 16 patients (17.0%) had a complete response, and 40 patients (42.6%) had partial responses. The response rate was 59.6% (95% CI, 49.0-69.6%). The median time to progression and overall survival times were 11.7 and 40.3 months, respectively. The toxicity was mild and tolerable, and the related grade 3/4 clinical adverse effects consisted of haematological toxicity in 21 patients (22%) and nonhaematological toxicity in five patients (5%). These results suggest that the oral combination chemotherapy of 5'-DFUR and CPA has low toxicity and is a novel, very convenient and effective treatment for metastatic breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Administração Oral , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclofosfamida/uso terapêutico , Feminino , Floxuridina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Pró-Fármacos/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
16.
Ann Oncol ; 14(8): 1234-40, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12881385

RESUMO

BACKGROUND: Breast cancer has been the subject of many recent studies because it is a significant cause of death in women. This study was performed to clarify whether solitary skeletal metastasis has clinical significance compared with multiple skeletal metastasis. PATIENTS AND METHODS: Seven hundred and three patients who developed metastatic bone lesions up to September 2002 after beginning treatment for breast cancer from 1988 to 1998 were included. The lesions were classified first as solitary or multiple based on bone scan results and then according to anatomical distribution. Next, solitary-to-multiple conversion was investigated in patients with solitary skeletal metastasis. Then factors related to solitary or multiple skeletal metastasis were analyzed. The prognosis of skeletal metastasis was compared between patients with solitary or multiple metastatic bone lesions. A Cox proportional hazards model was used to test whether solitary skeletal metastasis compared with multiple skeletal metastasis was an independent factor of survival. RESULTS: Two hundred and eighty-nine patients (41%) had solitary skeletal metastasis and 414 patients (59%) showed multiple skeletal metastasis. The sternum was a frequent site for solitary skeletal metastasis (98 of 289, 34%), while other skeletal sites were more frequent in patients with multiple metastatic bone lesions (P <0.001). Solitary sternal metastatic lesions remained solitary longer than solitary metastatic bone lesions to places other than the sternum (P <0.001), but did not lengthen patient survival times (P = 0.871). The factors related to solitary skeletal metastasis are TNM stage (tumor-node-metastasis) and histology. The patients with earlier stage and favorable histology tend to have solitary skeletal metastasis. The patients with solitary skeletal metastasis lived longer than those with multiple metastatic bone lesions (P <0.001). Multivariate analysis revealed that a solitary metastatic bone lesion (P = 0.002) is an independent favorable prognostic factor in patients with skeletal metastasis. CONCLUSIONS: Solitary skeletal metastasis has a different anatomical distribution and is an independent prognostic factor in patients with skeletal metastasis.


Assuntos
Neoplasias Ósseas/classificação , Neoplasias Ósseas/secundário , Neoplasias da Mama/classificação , Adulto , Idoso , Análise de Variância , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Estudos de Coortes , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Probabilidade , Modelos de Riscos Proporcionais , Cintilografia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Taxa de Sobrevida
17.
Nucl Med Commun ; 24(6): 663-70, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12766602

RESUMO

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Compostos Radiofarmacêuticos , Rênio , Biópsia de Linfonodo Sentinela/métodos , Compostos de Tecnécio , Adulto , Idoso , Neoplasias da Mama/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfonodos/metabolismo , Metástase Linfática , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Rênio/administração & dosagem , Rênio/farmacocinética , Sensibilidade e Especificidade , Compostos de Tecnécio/administração & dosagem , Compostos de Tecnécio/farmacocinética
18.
Biomed Pharmacother ; 56 Suppl 1: 201s-204s, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12487282

RESUMO

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar/métodos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Mastectomia Segmentar/estatística & dados numéricos , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
19.
Intern Med ; 40(9): 956-60, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11579965

RESUMO

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Melanoma/genética , Melanoma/secundário , Neoplasias Primárias Desconhecidas/genética , Translocação Genética , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 8/genética , Feminino , Humanos , Japão , Cariotipagem , Melanoma/diagnóstico por imagem , Melanoma/patologia , Tomografia Computadorizada por Raios X
20.
Int J Hematol ; 74(1): 64-9, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11530807

RESUMO

Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of developing cancers. However, it is extremely rare that synchronous double cancers develop in an MDS patient. We report a case of MDS that progressed rapidly into erythroleukemia (M6 by French-American-British classification) complicated by gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with refractory anemia with excess of blasts in transformation [RAEB-T]) was made by bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric cancer was also diagnosed by endoscopic examination. The peripheral blasts gradually proliferated and the disease progressed to M6. A chromosome abnormality 46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen was started as a remission-induction therapy. However, obstructive jaundice developed and a marked dilatation of bile ducts was observed by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was detected by endoscopy. As remission was achieved and the pancytopenia improved, the patient subsequently underwent a surgical jejuno-choledochostomy to manage the jaundice. However, the leukemia relapsed thereafter and additional chromosome abnormalities including der(5)t(5;10)(p15:q11) were observed.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Anemia Refratária com Excesso de Blastos , Neoplasias do Ducto Colédoco , Leucemia Eritroblástica Aguda , Neoplasias Primárias Múltiplas , Neoplasias Gástricas , Aclarubicina/administração & dosagem , Adenocarcinoma/complicações , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Colestase Extra-Hepática/etiologia , Aberrações Cromossômicas , Transtornos Cromossômicos , Neoplasias do Ducto Colédoco/complicações , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/cirurgia , Citarabina/administração & dosagem , Progressão da Doença , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Cariotipagem , Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patologia , Masculino , Neoplasias Primárias Múltiplas/genética , Segunda Neoplasia Primária , Pancitopenia/etiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
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