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1.
Int J Oral Maxillofac Surg ; 44(1): 16-22, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25444479

RESUMO

The objective of this study was to analyze the oncological and functional outcomes after the surgical treatment of parotid cancer. We reviewed 80 primary parotid carcinomas retrospectively. A superficial parotidectomy was performed in 10 patients; 27 patients underwent total parotidectomy and 43 patients underwent radical parotidectomy. A facial-facial nerve anastomosis was chosen for the facial nerve reconstruction in eight patients, while an interpositional graft was selected in 24 patients. The overall N-positive rate of pathology was 21.3%. The rate of occult metastasis was 8.1%. High-grade carcinoma and lymphovascular emboli were independent factors for nodal metastasis. The 5-year disease-free survival and overall survival rates were 79.7% and 78.8%, respectively. Preoperative facial nerve palsy and extraparenchymal invasion were the independent factors associated with poor disease-free survival. Of the 41 patients in the facial nerve preservation group, 13 (31.7%) had transient facial nerve paresis. In the facial nerve sacrifice group of 39 cases, (sub)total recovery (House-Brackmann grade I/II) occurred in 14 (35.9%), partial recovery (House-Brackmann grade III/IV) in 13 (33.3%), and no recovery (House-Brackmann grade V) in 12 (30.8%). Facial nerve palsy upon presentation and extraparenchymal invasion indicate a grave prognosis. Facial nerve function after proper reconstruction is tolerable.


Assuntos
Neoplasias Parotídeas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Paralisia Facial/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Procedimentos Cirúrgicos Bucais , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Procedimentos de Cirurgia Plástica , Recuperação de Função Fisiológica , Estudos Retrospectivos , Taxa de Sobrevida
2.
Int J Oral Maxillofac Surg ; 43(6): 674-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24393570

RESUMO

Preoperative radiological evaluation of the extent of local invasion in maxillary squamous cell carcinoma (SCC) is very important in planning curative surgery. The aim of this study was to examine the accuracy of preoperative radiological evaluation with magnetic resonance imaging (MRI) for the extent of local invasion in maxillary SCC. A retrospective study was conducted of 33 patients who underwent a maxillectomy for maxillary SCC. We compared the MRI findings for 18 structures around the maxillary sinus with intraoperative or postoperative pathological findings. Discrepancies were found between preoperative MRI findings and intraoperative or postoperative pathological findings for 22 patients (66.7%). Overall, the specificity, sensitivity, positive predictive value, and negative predictive value of MRI were 83.4%, 83.0%, 64.5%, and 90.4%, respectively. The receiver operating characteristic curve showed that MRI evaluation of the posterolateral structures including the pterygoid plate, pterygoid muscle, and infratemporal fossa had a lower area under the curve (0.614) and a significantly lower accuracy when compared with the other structures (P = 0.294, 95% confidence interval 0.405-0.822). In conclusion, as the accuracy of preoperative MRI evaluation of the posterolateral structures is low, careful evaluation of local extension to the posterolateral structures is needed when planning curative surgery for maxillary SCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Imageamento por Ressonância Magnética , Neoplasias Maxilares/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Neoplasias Maxilares/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Sensibilidade e Especificidade
3.
Br J Ophthalmol ; 93(7): 958-63, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19028740

RESUMO

BACKGROUND: To investigate the effect of orally administered sorafenib, a multikinase inhibitor, in a mouse model of choroidal neovascularisation (CNV). METHODS: Sorafenib or vehicle was administered orally to female C57BL/6 mice at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the following day. After 14 days, mice were perfused with fluorescein-labelled dextran, and the area of CNV was measured on choroidal flat mounts by image analysis. In some groups of mice, treatments were started 7 days after the laser photocoagulation to determine the effect of the agent on established CNV. Expression of phosphorylated extracellular signal-regulated kinase (p-ERK) in choroidal tissues was measured by Western blot analysis to demonstrate the kinase-inhibitory effect of sorafenib in intracellular signalling pathways involved in CNV formation. RESULTS: Sorafenib significantly reduced the extent of CNV in a dose-dependent manner. The area of CNV was reduced by 43% in the 30 mg/kg/day group and by 61% in the 60 mg/kg/day group compared with vehicle-treated controls (both p<0.0001). Oral administration of sorafenib also caused significant regression of established CNV. The area of CNV was reduced by 59% in the 30 mg/kg/day group and by 66% in the 60 mg/kg/day group compared with both baseline and control measurements (p<0.0001). The expression of p-ERK in choroidal tissues was increased within 1 day of laser photocoagulation and remained elevated for 2 weeks. The expression of p-ERK was suppressed by sorafenib. CONCLUSIONS: Sorafenib demonstrated antiangiogenic properties in a mouse model of CNV and may be useful in the treatment of CNV.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Benzenossulfonatos/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Piridinas/administração & dosagem , Administração Oral , Animais , Western Blotting , Dextranos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Fluoresceínas/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sorafenibe
4.
Eye (Lond) ; 22(7): 895-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17435692

RESUMO

PURPOSE: To investigate the progression of cataract after a high dose (25 mg) intravitreal triamcinolone acetonide injection in patients with macular oedema secondary to diabetes and retinal vein occlusion. METHODS: This prospective interventional case series study included 38 patients (76 eyes) with diabetic retinopathy or retinal vein occlusion diagnosed with clinical examination and fluorescein angiography. The patients were treated with 25 mg IVTA in their one eye with macular oedema and the fellow eyes served as a control. Patients were asked to return the next day and weekly for 1 month and monthly thereafter by 6 months post-operative. The progression of the cataract using photographic evaluation according to the Lens Opacities Classification System III was documented and statistical analysis was done using the Kaplan-Meier survival analysis and the log-rank test. RESULTS: Among the 38 treated eyes, there was an increase of cataract degree by 1 grade at the end of 6 months in 10 patients. The types of progressed cataract were PSC in seven patients, cortical in six patients, and nuclear sclerosis in one patient. Six months after the injections, there was a significantly higher rate of progression of PSC (P=0.023, log-rank test) and cortical opacities (P=0.011) in the treated group while the progression of nuclear cataract was not significantly different between the treated eye and the control eye. CONCLUSION: A high-dose (25 mg) intravitreal triamcinolone acetonide injection induces the progression of cortical and posterior subcapsular opacity in patients with diabetic macular oedema and retinal vein occlusion.


Assuntos
Catarata/induzido quimicamente , Glucocorticoides/efeitos adversos , Triancinolona Acetonida/efeitos adversos , Idoso , Retinopatia Diabética/tratamento farmacológico , Progressão da Doença , Esquema de Medicação , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Injeções , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/uso terapêutico , Acuidade Visual/efeitos dos fármacos , Corpo Vítreo
5.
Leukemia ; 21(12): 2476-84, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17851558

RESUMO

Deregulated accumulation of nuclear beta-catenin enhances transcription of beta-catenin target genes and promotes malignant transformation. Recently, acute myeloid leukemia (AML) cells with activating mutations of FMS-like tyrosine kinase-3 (FLT3) were reported to display elevated beta-catenin-dependent nuclear signaling. Tyrosine phosphorylation of beta-catenin has been shown to promote its nuclear localization. Here, we examined the causal relationship between FLT3 activity and beta-catenin nuclear localization. Compared to cells with wild-type FLT3 (FLT3-WT), cells with the FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain mutation (FLT3-TKD) had elevated levels of tyrosine-phosphorylated beta-catenin. Although beta-catenin was localized mainly in the cytoplasm in FLT3-WT cells, it was primarily nuclear in FLT3-ITD cells. Treatment with FLT3 kinase inhibitors or FLT3 silencing with RNAi decreased beta-catenin tyrosine phosphorylation and nuclear localization. Conversely, treatment of FLT3-WT cells with FLT3 ligand increased tyrosine phosphorylation and nuclear accumulation of beta-catenin. Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide/metabolismo , Proteínas de Neoplasias/fisiologia , Processamento de Proteína Pós-Traducional/fisiologia , Transcrição Gênica/fisiologia , beta Catenina/metabolismo , Tirosina Quinase 3 Semelhante a fms/fisiologia , Doença Aguda , Animais , Linhagem Celular Tumoral , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/fisiologia , Glicogênio Sintase Quinase 3 beta , Humanos , Interleucina-3/farmacologia , Leucemia Mieloide/genética , Leucemia Mieloide/patologia , Proteínas de Membrana/farmacologia , Camundongos , Proteínas de Neoplasias/antagonistas & inibidores , Fosforilação , Fosfotirosina/metabolismo , RNA Interferente Pequeno/farmacologia , Proteínas Recombinantes/metabolismo , Estaurosporina/análogos & derivados , Estaurosporina/farmacologia , Tirfostinas/farmacologia , beta Catenina/genética , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/genética
9.
Yonsei Med J ; 42(2): 220-6, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11371111

RESUMO

omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer.


Assuntos
Ácidos Graxos/metabolismo , Mucosa Gástrica/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Ácido Araquidônico/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/metabolismo
10.
Radiat Environ Biophys ; 40(4): 335-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11820743

RESUMO

The aim of the study was to investigate the effect of low doses of irradiation on the induction of an apoptotic adaptive response in the murine system using C3H/HeJ mice bearing 8 mm syngeneic tumors, HCa-I and OCa-I. In OCa-I, the 0.05 Gy priming dose significantly reduced the 25 Gy-induced apoptosis by 30%, whereas this reduction was not seen in HCa-I. The analysis of apoptosis-regulating molecules showed that the application of a priming dose increased the radiation-induced p53 level in both tumors. No other regulators changed in OCa-I. However, in HCa-I, the application of a priming dose increased radiation-induced Bcl-XL and Bcl-XS, but not Bcl-2 or Bax. An apoptotic adaptive response induced by low-dose radiation was shown in one murine tumor, OCa-I and Bcl-XL and Bcl-XS appeared to be implicated.


Assuntos
Apoptose/efeitos da radiação , Animais , Western Blotting , Fragmentação do DNA , Relação Dose-Resposta à Radiação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Células Tumorais Cultivadas
11.
Cell Immunol ; 204(1): 46-54, 2000 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-11006017

RESUMO

Transforming growth factor-beta (TGF-beta) has been known as a potent immunosuppressive cytokine that can induce apoptosis in lymphoid cells. We established an IL-2-independent cell line, CTLL-2A, from murine T cell line CTLL-2. CTLL-2A expressed higher levels of CD95, CD69, and CD18 molecules than CTLL-2 did, suggesting a more activated state in CTLL-2A than in the CTLL-2 by phenotype. Exposing both CTLL-2 and CTLL-2A to TGF-beta results in differential apoptosis patterns defined by DNA fragmentation and plasma membrane alteration. Among the bcl-2 family members, bcl-2, bcl-w, and bcl-x(L) were also differently expressed in these two cell lines. In CTLL-2A, bcl-x(L) was amplified as a major anti-apoptotic molecule, and TGF-beta-induced cell death was more enhanced than in the original cell line. Caspase 1-like protease was activated by TGF-beta treatment and consequently it cleaved bcl-x(L) in CTLL-2A. TGF-beta-induced DNA fragmentation and cleavage of bcl-x(L) were inhibited by pretreatment with tetra peptide caspase 1 inhibitor, YVAD.cmk. These findings suggest that TGF-beta induces cell death in activated murine T cells through cleavage of bcl-x(L) via activated caspase 1-like protease, which may act as an important executor in that process.


Assuntos
Apoptose , Caspase 1/metabolismo , Linfócitos T/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Caspase 3 , Inibidores de Caspase , Linhagem Celular , Ativação Enzimática , Regulação da Expressão Gênica , Interleucina-2/farmacologia , Membranas Intracelulares/metabolismo , Potenciais da Membrana , Camundongos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína bcl-X
12.
Mol Cells ; 10(4): 399-404, 2000 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-10987136

RESUMO

Non-redundant expressed sequence tags (ESTs) were generated from six different organs at various developmental stages of Chinese cabbage, Brassica rapa L. ssp. pekinensis. Of the 1,295 ESTs, 915 (71%) showed significantly high homology in nucleotide or deduced amino acid sequences with other sequences deposited in databases, while 380 did not show similarity to any sequences. Briefly, 598 ESTs matched with proteins of identified biological function, 177 with hypothetical proteins or non-annotated Arabidopsis genome sequences, and 140 with other ESTs. About 82% of the top-scored matching sequences were from Arabidopsis or Brassica, but overall 558 (43%) ESTs matched with Arabidopsis ESTs at the nucleotide sequence level. This observation strongly supports the idea that gene-expression profiles of Chinese cabbage differ from that of Arabidopsis, despite their genome structures being similar to each other. Moreover, sequence analyses of 21 Brassica ESTs revealed that their primary structure is different from those of corresponding annotated sequences of Arabidopsis genes. Our data suggest that direct prediction of Brassica gene expression pattern based on the information from Arabidopsis genome research has some limitations. Thus, information obtained from the Brassica EST study is useful not only for understanding of unique developmental processes of the plant, but also for the study of Arabidopsis genome structure.


Assuntos
Brassica/genética , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Genoma de Planta , Arabidopsis/genética , Bases de Dados como Assunto , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico
13.
Int J Radiat Oncol Biol Phys ; 46(3): 639-43, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10701743

RESUMO

PURPOSE: Radiation of the liver results in hepatic fibrosis as a late complication. TGF-beta has been implicated in the pathogenesis of fibrosis. The purpose of this study was to determine if there is early alteration in TGF-beta expression before hepatic fibrosis is evident. METHODS AND MATERIALS: Male Sprague-Dawley rats weighing 150-175 g were used. A partial volume of liver as large as a 2 cm x 1 cm rectangle was given a single dose of 25 Gy gamma radiation. Animals were sequentially sacrificed from day 0 to day 28. Appearance of hepatic fibrosis was tested by trichrome stain. Levels of mRNA expression of TGF-beta1 and TGF-beta3 were measured by Northern blot hybridization. Change in the level of mRNA expression was analyzed by densitometry. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. RESULTS: In trichrome-stained liver tissues obtained through 28 days after irradiation, there was no evidence of hepatic fibrosis. The expression of mRNAs of TGF-beta1 and TGF-beta3 showed different features; The level of TGF-beta1 mRNA showed a gradual increase to the peak level of 3.6-fold at day 28, the last analyzed time. In contrast, TGF-beta3 mRNA showed an early peak of 4.8-fold at day 7 followed by a decrease to the lowest level of 1.6-fold at the last analyzed time. The expression of TGF-betas was also analyzed in tissue with immunohistochemical staining. At day 28 after radiation, increased positive staining for TGF-beta1 was observed around the central vein. Positive staining appeared mainly in nonhepatocytic cells. For TGF-beta3, the same pattern of positive staining was observed at day 7. CONCLUSION: The results of this study suggest that the alteration in mRNA expression of TGF-beta1 and TGF-beta3 occurs very early after radiation. The contrasting difference in the mRNA expression pattern of TGF-beta1 and TGF-beta3 suggests that interaction of the TGF-betas may be involved in fibrogenesis of irradiated liver, with TGF-beta1 as a positive regulator and TGF-beta3 as a negative regulator.


Assuntos
Fígado/efeitos da radiação , RNA Mensageiro/efeitos da radiação , Fator de Crescimento Transformador beta/efeitos da radiação , Animais , Biomarcadores , Fígado/metabolismo , Cirrose Hepática Experimental/etiologia , Masculino , RNA Mensageiro/metabolismo , Doses de Radiação , Lesões Experimentais por Radiação/etiologia , Radiobiologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Fator de Crescimento Transformador beta/metabolismo
14.
J Clin Oncol ; 18(1): 54-63, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10623693

RESUMO

PURPOSE: To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS: We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS: The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION: Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Linfoma/radioterapia , Análise Atuarial , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Coreia (Geográfico)/epidemiologia , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radioterapia/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
15.
Am J Otolaryngol ; 20(6): 383-90, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10609483

RESUMO

PURPOSE: To further clarify the clinical significance of neck node metastasis in squamous cell carcinoma of the maxillary sinus (maxillary SCC). MATERIALS AND METHODS: The medical charts of the 116 patients with maxillary SCC were retrospectively reviewed. Twelve patients (10.3%) presented initially with neck node metastases, and 14 (13.5%) of 104 node-negative patients subsequently developed regional recurrence during the follow-up period. The high-risk factors for neck node metastasis, patterns of regional failure, and survival for node-positive patients were analyzed with the patient cohort that had largely been treated with radiation alone. RESULTS: Of the various factors, the tumor extension to the nasopharynx or oral cavity was the statistically significant determinants predictive of neck node metastasis at the initial diagnosis. During the follow-up period, regional failure was far less common than local failure (19.0% v 68.1%), and the majority of regional failures were accompanied by local recurrences. The oral cavity extension and control status of local disease were the high-risk factors for subsequent development of regional recurrence in node-negative patients. The overall 5-year survival rate for node-positive patients (16.7%) showed a poorer outcome compared with that for node-negative patients (31.3%), but it was similar to that of T4N0 patients (26.6%). Although patients who subsequently developed neck node recurrence during follow-up represented a dismal prognosis, uncontrolled local diseases in these patients still remained a major problem, resulting in a poor prognosis. CONCLUSIONS: Despite an unfavorable prognosis of patients with neck node metastasis, an aggressive trial to achieve maximum local control of the primary tumor was considered to be more important than elective neck treatments.


Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias do Seio Maxilar/patologia , Adulto , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Metástase Linfática , Masculino , Neoplasias do Seio Maxilar/radioterapia , Neoplasias do Seio Maxilar/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Segunda Neoplasia Primária , Prognóstico , Estudos Retrospectivos
16.
Int J Radiat Oncol Biol Phys ; 45(5): 1167-73, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10613309

RESUMO

PURPOSE: Recurrent colorectal cancers respond poorly to anticancer treatment including radiotherapy. To better understand the biological characteristics of the recurrent colorectal tumor, we investigated various biomarkers regulating cell proliferation and cell loss in paired primary and recurrent colorectal tumor specimens within each individual. METHODS AND MATERIALS: From a total of 11 colorectal adenocarcinoma patients, 22 specimens of paired primary and recurrent tumors were obtained for analysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragmentation. Other biomarkers including proliferating cell nuclear antigen (PCNA), p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistochemical stains. RESULTS: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 recurrent tumors compared to primary tumors. Median PCNAI in primary and recurrent tumors were 33.5 and 48.3, respectively (p = 0.16). In contrast, the apoptotic index (AI) decreased in 9 of 11 recurrent tumors compared to primary tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurrent tumors (p = 0.04). The p53 expression increased in more than half of recurrent tumors compared to primary tumors. Mean staining score increased from 0.7 in primary tumors to 1.2 in recurrent tumors (p = 0.059). WAF1 and cyclin B1 did not show significant change. In contrast, both cyclin D1 and p34cdc2 increased significantly in recurrent tumors. These two biomarkers showed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors, respectively, compared to their primary counterparts. Mean staining scores of both biomarkers in recurrent tumors increased by more than twofold compared to those in primary tumors and these differences were statistically significant (cyclin D1, p = 0.007; p34cdc2, p = 0.008). CONCLUSION: This study showed significantly decreased apoptosis in recurrent colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further study, it may be used for developing a new therapeutic strategy for the treatment of recurrent colorectal cancer.


Assuntos
Apoptose , Biomarcadores Tumorais/análise , Neoplasias do Colo/química , Recidiva Local de Neoplasia/química , Neoplasias Retais/química , Adulto , Idoso , Apoptose/genética , Proteína Quinase CDC2/análise , Divisão Celular , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Ciclina B/análise , Ciclina B1 , Ciclina D1/análise , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/análise , Fragmentação do DNA , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Antígeno Nuclear de Célula em Proliferação/análise , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias do Colo Sigmoide/química , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/patologia , Proteína Supressora de Tumor p53/análise
17.
Pathobiology ; 67(3): 123-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10394132

RESUMO

The mechanisms underlying the impaired immune response frequently observed in cancer patients are not fully understood. Alteration of T-cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. Furthermore, T cells from tumor-bearing host, irrespective of the presence of the zeta-chain, showed a lack of proliferative activity and cytotoxic function. In the present study, we investigated the expression of the zeta-chain molecule and the p56(lck) and p59(fyn) protein tyrosine kinase (PTK) levels in peripheral blood T lymphocytes (T-PBL) from patients with advanced gastric carcinomas; for this, flow cytometric analysis and immunoblotting, respectively, were used. We also compared the results of flow cytometric analysis of PBL between stomach cancer patients and normal healthy volunteers. In T-PBL from 22 tumor-bearing hosts, significantly reduced zeta-chain expression (16/22, 73%) was observed. Moreover, the expression level of p56(lck) in T-PBL from patients was significantly lower than that of p59(fyn). Flow cytometric analysis of T-PBL indicated a markedly increased CD8+28- cell population in T-PBL from 19 tumor-bearing hosts.


Assuntos
Linfócitos/imunologia , Transdução de Sinais/imunologia , Neoplasias Gástricas/imunologia , Adulto , Idoso , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Contagem de Linfócitos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Linfócitos/citologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-fyn , Complexo Receptor-CD3 de Antígeno de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Neoplasias Gástricas/sangue , Linfócitos T/citologia , Linfócitos T/imunologia
18.
Acta Oncol ; 38(4): 449-54, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10418711

RESUMO

The purpose of this study was to investigate the correlation between the spontaneous apoptotic index (SAI) determined from pretreatment biopsy specimens with the various clinical outcomes of patients with FIGO stage IIB squamous cell carcinoma of the uterine cervix in a retrospective analysis. Forty-eight patients treated with curative radiotherapy between 1989 and 1993 were evaluated. Pretreatment biopsy specimens of those patients were scored for apoptosis, mitosis, and proliferating cell nuclear antigen (PCNA) immunohistochemical staining. The range of the SAI was 0.2-4.7% (median 1.1%). Patients whose tumours had a SAI above the median had better local control (p = 0.0062) and overall survival (p = 0.0053) than those with a lower SAI. Furthermore, the SAI was marginally significant on local control by a multivariate Cox regression analysis (p = 0.0571). There was no correlation between the SAI and proliferation (mitosis and PCNA).


Assuntos
Apoptose/fisiologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
19.
Int J Radiat Oncol Biol Phys ; 41(4): 835-41, 1998 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-9652846

RESUMO

PURPOSE: To investigate the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Anorectal manometry was carried out on 24 patients (complication group) with late radiation proctitis. All of the manometric data from these patients were compared with those from 24 age-matched female volunteers (control group), in whom radiation treatment had not yet been performed. RESULTS: Regardless of the severity of proctitis symptoms, 25% of patients demonstrated all their manometric data within the normal range, but 75% of patients exhibited one or more abnormal manometric parameters for sensory or motor functions. Six patients (25%) had an isolated sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction, and four patients (16.7%) had combined disturbances of both sensory and motor functions. The maximum tolerable volume, the minimal threshold volume, and the urgent volume in the complication group were significantly reduced compared with those in the control group. The mean squeeze pressure in the complication group was significantly reduced, whereas the mean resting pressure and anal sphincter length were unchanged. CONCLUSIONS: Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction.


Assuntos
Canal Anal/fisiopatologia , Proctite/fisiopatologia , Lesões por Radiação/fisiopatologia , Transtornos de Sensação/fisiopatologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Canal Anal/efeitos da radiação , Feminino , Humanos , Manometria , Pessoa de Meia-Idade
20.
Cancer Immunol Immunother ; 45(6): 299-305, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9490199

RESUMO

Tumor development or growth is accompanied by impaired immune responses, such as a poor proliferative response or down-regulated cytolytic T lymphocyte activity. Although recent reports have suggested that modification of the signal-transducing molecule is responsible for impaired immune responses in tumor-bearing hosts, the causes of defective immune function are not yet completely understood. Furthermore, the clinical significance of the findings is not yet clear. In this study, we investigated the alteration of several signal-transducing molecules in peripheral blood T lymphocytes (T-PBL) as well as in tumor-infiltrating lymphocytes (TIL) from human colorectal carcinoma patients and their relationship with the impaired host immune responses. A greater reduction in CD3zeta chain level was observed in TIL than in T-PBL from tumor-bearing hosts. CD3zeta chain reduction in T-PBL correlated with the clinicopathological stage of a tumor, especially with the status of lymph node metastasis. The levels of p56lck and p59fyn protein tyrosine kinase in T-PBL were also compared between tumor-bearing hosts and normal healthy volunteers. In T-PBL from tumor-bearing hosts, expression of protein tyrosine kinase p59fyn was significantly lower than that of p56lck. However, the level of CD3zeta chain expression did not correlate with T lymphocyte functions such as T lymphocyte proliferative response or allogeneic target cell lysis.


Assuntos
Complexo CD3/metabolismo , Carcinoma/imunologia , Neoplasias Colorretais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T/imunologia , Complexo CD3/química , Concanavalina A/farmacologia , Humanos , Ativação Linfocitária , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-fyn , Transdução de Sinais
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