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1.
Clin Otolaryngol ; 43(4): 1117-1121, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29679522

RESUMO

OBJECTIVES: Inflammation is known to be associated with the progression of cancer. The study was designed to characterise the systemic inflammation in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigate its relation to tumour size, ability to metastasise and HPV status. MATERIALS AND METHODS: Blood was obtained from 58 patients with OPSCC and 90 healthy controls and analysed with leucocyte differential count. RESULTS: The patients with OPSCC displayed an increased number of neutrophils and monocytes, whereas the lymphocytes were suppressed compared to the healthy controls. The neutrophils-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MLR) were calculated, and patients with large tumours exhibited high NLR and MLR. Further, patients with regional lymph node spread displayed a low NLR and MLR. Patients with HPV-positive tumours (n = 48) had a lower NLR than the patients (n = 8) with HPV-negative tumours. CONCLUSION: This study demonstrates that patients with OPSCC have an increased systemic inflammation that is affected by the HPV status, the size of the tumour and lymph node spread.

2.
Int J Oral Maxillofac Surg ; 49(1): 1-6, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31296436

RESUMO

Better cancer treatment has led to a steadily growing population of cancer survivors suffering from late adverse effects after cancer treatment. The aim of this study was to investigate whether there has been an increase in free flap reconstruction due to osteoradionecrosis (ORN). A retrospective review was conducted to identify all consecutive head and neck free flap reconstructions performed over an 18-year period (1995-2012) at Karolinska University Hospital. A total of 235 free flaps were identified. Cases were divided into two groups: head and neck cancer reconstructions and ORN reconstructions. A comparison between the two groups showed longer survival (P<0.001) and higher rates of late complications (P<0.001) among ORN cases. ORN as an indication for reconstruction increased over time, from 7.0% of the total number of free flaps performed in 1995-2000, to 15.2% during the period 2001-2006, and to 27.3% in 2007-2012 (P<0.001). This, in accordance with the results of other studies, highlights the importance of the appropriate allocation of resources within the healthcare system to treat this patient group within the steadily increasing population of cancer survivors.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Osteorradionecrose , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos
3.
Br J Cancer ; 99(7): 1121-8, 2008 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-18766188

RESUMO

Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer associated with poor prognosis. Methods for determining the aggressiveness of OTSCC from analysis of the primary tumour specimen are thus highly desirable. We investigated whether genomic instability and proliferative activity (by means of Ki-67 activity) could be of clinical use for prediction of locoregional recurrence in 76 pretreatment OTSCC paraffin samples (stage I, n=22; stage II, n=33; stage III, n=8; stage IV, n=13). Eleven surgical tumour specimens were also analysed for remnants of proliferative activity after preoperative radiotherapy. Ninety-seven percent of cases (n=72) were characterised as being aneuploid as measured by means of image cytometry. Preoperative radiotherapy (50-68 Gy) resulted in significant reduction of proliferative activity in all patients for which post-treatment biopsies were available (P-value=0.001). Proliferative activity was not associated with response to radiation in stage II patients. However, we report a significant correlation between high proliferation rates and locoregional recurrences in stage I OTSCC patients (P-value=0.028). High-proliferative activity is thus related to an elevated risk of recurrence after surgery alone. We therefore conclude that Ki-67 expression level is a potentially useful clinical marker for predicting recurrence in surgically treated stage I OTSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Antígeno Ki-67/sangue , Recidiva Local de Neoplasia , Neoplasias da Língua/patologia , Adulto , Carcinoma de Células Escamosas/sangue , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Neoplasias da Língua/sangue
4.
Int J Radiat Oncol Biol Phys ; 45(5): 1259-66, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10613321

RESUMO

PURPOSE: This retrospective study was done to determine the outcome of patients with tonsillar carcinoma treated at Radiumhemmet, Karolinska Hospital, between January 1980 and December 1995 with radiotherapy alone or in combination with surgery. In addition the importance of tumor remission for patient survival was analyzed. METHODS AND MATERIALS: The analysis is based on 167 previously untreated patients with biopsy-proven, invasive tonsillar squamous cell carcinoma of the tonsillar region. All patients were consecutively admitted to the Department of General Oncology, Radiumhemmet, and treated with curative intent. The median follow-up time was 20 months. The median target dose was 64 Gy, delivered in fractions of 2 Gy 5 times weekly. Twenty-eight percent of the patients underwent surgery of the primary site and/or neck dissection after radiotherapy (RT). RESULTS: The overall local control rate for the whole patient group after radiotherapy was 79%. Probability of survival after 5 years for patients responding with complete remission (CR) was 43% and for patients with incomplete response (non-CR) 9%, (p<0.0001). The survival in the non-CR group treated with combination therapy was 20 months longer than in patients receiving radiotherapy alone (p<0.0001). There was no statistically significant difference in prediction of long-term survival when the patient population was stratified according to tumor differentiation grade, age, sex, nodal status, or treatment time. CONCLUSION: The strongest clinical predictor of survival was the degree of tumor remission after RT. For the non-CR group receiving combination treatment including surgery there was a survival benefit as compared to patients treated with RT alone (p<0.0001) although there were few long-term survivors in this patient group.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Tonsilares/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Seguimentos , Humanos , Estadiamento de Neoplasias , Seleção de Pacientes , Cuidados Pré-Operatórios , Prognóstico , Dosagem Radioterapêutica , Recidiva , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/cirurgia
5.
Radiother Oncol ; 24(2): 114-6, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1379740

RESUMO

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.


Assuntos
Bleomicina/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Esofágicas/radioterapia , Idoso , Bleomicina/administração & dosagem , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Deglutição/efeitos dos fármacos , Deglutição/fisiologia , Deglutição/efeitos da radiação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Países Escandinavos e Nórdicos/epidemiologia , Taxa de Sobrevida
6.
Int J Oncol ; 12(4): 859-64, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9499447

RESUMO

Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer.


Assuntos
Neoplasias Laríngeas/metabolismo , Metaloproteinase 3 da Matriz/genética , Lesões Pré-Cancerosas/metabolismo , RNA Mensageiro/análise , Humanos
7.
J Clin Pathol ; 52(1): 35-40, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10343610

RESUMO

AIM: To assess the clinical value of malignancy grading systems compared with nuclear DNA content, protein p53, and angiogenesis for predicting recurrence of stage I (UICC, 1987) tongue carcinomas. METHODS: Histopathological malignancy grading according to Jakobsson and tumour front grading according to Bryne et al were performed on haematoxylin and eosin slides. DNA analysis was performed by image cytometry. Protein p53 and angiogenesis were evaluated by immunohistochemical analysis using antibody CM1 and antibody against factor VIII related antigen, respectively. RESULTS: 49 patients with stage I carcinomas of the mobile tongue were included, all treated by local surgical excision alone. Eight patients (16%) suffered from local recurrence during follow up, and 13 (27%) had regional recurrence. Both Jakobsson's malignancy grading system and p53 immunoreactivity proved to be useful predictors of regional recurrence in a Cox multivariate regression analysis. CONCLUSIONS: Histopathological malignancy grading systems provide valuable prognostic information and can still compete with current biological markers in this respect.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Neovascularização Patológica/patologia , Neoplasias da Língua/patologia , Proteína Supressora de Tumor p53/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Prognóstico , Recidiva , Neoplasias da Língua/irrigação sanguínea , Neoplasias da Língua/cirurgia
8.
Virchows Arch ; 424(4): 343-7, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8205349

RESUMO

This paper describes the investigation of nuclear DNA content and p53 immunoreactivity in normal mucosa (n = 25), mildly (n = 15), moderately (n = 28) and severely atypical (n = 22) colorectal adenomas and in colorectal adenocarcinomas (n = 116). Twenty-seven per cent of the mildly atypical, 43% of the moderately, 77% of the severely atypical adenomas and 91% of the colorectal carcinomas were distinctly aneuploid. In the aneuploid lesions p53 immunoreactivity was not observed in mildly atypical adenomas, whereas 17% of the moderately atypical, 24% of the severely atypical adenomas and 66% of the adenocarcinomas were p53 positive. None of the diploid lesions were p53 immunoreactive. These data are interpreted to indicate that genomic instability as reflected by crude aneuploidy occurs early during genesis of colorectal carcinoma and represents a high risk factor for p53-gene mutation.


Assuntos
Adenocarcinoma/genética , Aneuploidia , Neoplasias Colorretais/genética , Genes p53 , Adenoma/genética , Adulto , Idoso , Feminino , Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade
9.
Anticancer Res ; 11(2): 597-600, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-2064313

RESUMO

The Feulgen-DNA content of cell nuclei from the human larynx was assessed in 62 lesions from 14 patients with dysplastic and cancerous lesions and in 14 control patients with non-neoplastic chronic laryngitis. All the carcinomas displayed aneuploid cell nuclei, and the cellular DNA content was substantially altered in dysplasias which later progressed to cancer in situ or invasive cancer. Thus the process of laryngeal carcinogenesis can be monitored not only by histological changes, but also by cellular DNA aberrations. Quantitative DNA analysis appears to be a complement to the histopathological evaluation of laryngeal lesions in the search for neoplasia.


Assuntos
DNA de Neoplasias/análise , DNA/análise , Neoplasias Laríngeas/patologia , Laringite/patologia , Laringe/patologia , Pólipos/patologia , Biópsia , Carcinoma in Situ/patologia , Núcleo Celular/ultraestrutura , Epitélio/patologia , Citometria de Fluxo/métodos , Humanos , Valores de Referência
10.
Anticancer Res ; 18(3B): 2063-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9677468

RESUMO

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified in the sera of 100 patients with sarcoma, head and neck carcinoma, oesophageal carcinoma, mesothelioma and lung carcinoma. VEGF and bFGF levels were generally higher in the sera of the tumor patients compared to the sera of healthy control subjects. Interestingly, VEGF and bFGF levels were generally not elevated in the same sera (p < 0.01), and covariation of the VEGF and the bFGF levels was only rarely observed during progressive disease, arguing for actual independence of factors. Very high levels of VEGF (668 pg/ml, n = 12) were observed in patients with mesothelioma, whereas bFGF levels were not increased in these patients. Our data suggest that VEGF levels increase with tumor progression and may be a useful marker for clinical monitoring of sarcoma and carcinoma patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , Fatores de Crescimento Endotelial/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Linfocinas/sangue , Sarcoma/sangue , Adulto , Idoso , Neoplasias Esofágicas/sangue , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/sangue , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
11.
Anticancer Res ; 10(3): 703-8, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2369087

RESUMO

The serum levels of Carcinoembryonic antigen, CA 19-9 and CA 50 were assessed in 60 patients with squamous cell carcinoma of the esophagus during the course of the disease. In 53 patients, the effect of preoperative or final treatment on tumor marker levels could be analysed, and the change in tumor marker levels discriminated significantly the patients who showed tumor mass/symptom regress from the patients who displayed progress or undecided change. Progress later in the course of the disease was reflected by a statistically significant increase in all three tumor marker assays, and in 8/18 (44%) patients the tumor marker increase was seen prior to other signs of tumor progression. The appearance of distant metastases was associated (11/12) with increase in CEA levels.


Assuntos
Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/terapia , Seguimentos , Humanos , Prognóstico , Radioimunoensaio , Fumar/sangue , Fumar/imunologia
12.
Anticancer Res ; 9(3): 545-9, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2764500

RESUMO

The Feulgen-DNA content of squamous carcinoma cell nuclei from the human esophagus was assessed in punch biopsies from 47 untreated patients. Forty-four of the 47 biopsies (93.6%) demonstrated aneuploid cell populations, and the remaining 3 (6.4%) were non-diploid. Previous studies have demonstrated that in esophageal dysplasias adjacent to invasive squamous cell carcinoma, DNA in single cells is substantially altered. Thus the process of esophageal carcinogenesis can be monitored not only by histological changes, but also by DNA aberrations in single cells. Quantitative DNA measurement appears, therefore, to be a complement to the histological evaluation of esophageal lesions with suspected, but not unequivocal, evidence of neoplastic growth.


Assuntos
Carcinoma de Células Escamosas/análise , DNA de Neoplasias/análise , Neoplasias Esofágicas/análise , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Diferenciação Celular , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Anticancer Res ; 18(5B): 3645-50, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9854471

RESUMO

BACKGROUND: Various mucosal lesions are frequently encountered in the oral cavity. Neither macroscopic nor microscopic evaluation of these lesions gives any reliable information concerning the risk of cancer development. MATERIAL AND METHODS: From 21 patients, 29 mucosal lesions were found to precede development of invasive squamous cell carcinoma or carcinoma in situ at the same location. The lesions were matched to 29 control lesions, with the same grade of dysplasia and from exactly the same locations but without subsequent cancer during a mean follow up of 112 months (46-194). The specimens were evaluated using Image Cytometry DNA analysis and immunohistochemical analysis of p53 and p21/WAF1 expression. RESULTS: Lesions prior to carcinomatous development displayed a higher degree of DNA aberration as compared with the control lesions. p53 and p21/WAF1 evaluation did not reveal any differences between cases and controls. CONCLUSION: Image Cytometry DNA analysis is an useful adjunct to histopathological evaluation of oral mucosal lesions for prediction of risk of malignant transformation.


Assuntos
Ciclinas/genética , DNA de Neoplasias/análise , Citometria por Imagem , Neoplasias Bucais/genética , Lesões Pré-Cancerosas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor de Quinase Dependente de Ciclina p21 , Progressão da Doença , Estudos de Avaliação como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica , Ploidias
14.
Anticancer Res ; 19(4C): 3409-14, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10629628

RESUMO

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.


Assuntos
Neoplasias/urina , Fragmentos de Peptídeos/urina , Plasminogênio/urina , Albuminúria , alfa-Globulinas/urina , Sequência de Aminoácidos , Angiostatinas , Western Blotting , Estudos de Casos e Controles , Densitometria , Neoplasias de Cabeça e Pescoço/urina , Humanos , Neoplasias Renais/urina , Kringles , Medições Luminescentes , Neoplasias Pulmonares/urina , Mesotelioma/urina , Dados de Sequência Molecular , Prognóstico , Sarcoma/urina
15.
Anticancer Res ; 21(1B): 529-34, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11299799

RESUMO

BACKGROUND: Human papilloma virus (HPV), which is frequently present in tonsillar carcinoma seems to be a prognostically favourable factor for patient survival and also for low risk of relapse. Since HPV may abrogate the function of wild type p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53 status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and patient survival. MATERIALS AND METHODS: Pre-treatment primary tonsillar carcinoma specimens were obtained retrospectively from 40 patients, 21 complete responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage III and IV tumours. The paraffin-embedded biopsies were analysed for presence of HPV DNA, by general and type specific PCR, and for p53 overexpression by immunohistochemical staining with the murine Mab DO-1. RESULTS: It was possible to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53 immunostaining (p53+) were not correlated with response to RT, since 8/18 CR patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR patients were p53+. A tendency towards a survival benefit in patients with HPV+ tumours was observed and this tendency was significant for patients with stage IV HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A difference in survival between patients with p53+ cancer as compared to patients with p53- lesions was not demonstrated. In conclusion, although presence of HPV and p53 immunoreactivity in tonsillar carcinoma could not be related to RT response, determination of HPV and p53 status may still prove useful as predictive/prognostic markers.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/virologia , Proteínas de Neoplasias/análise , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Radioterapia de Alta Energia , Neoplasias Tonsilares/virologia , Proteína Supressora de Tumor p53/análise , Infecções Tumorais por Vírus/virologia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genes p53 , Humanos , Técnicas Imunoenzimáticas , Tábuas de Vida , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Papillomaviridae/patogenicidade , Prognóstico , Tolerância a Radiação , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Tonsilares/química , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/radioterapia , Resultado do Tratamento , Proteína Supressora de Tumor p53/biossíntese
16.
Anticancer Res ; 19(4C): 3433-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10629631

RESUMO

BACKGROUND: The abrogation of the TP53 gene is considered to play a central role in the development of human cancers. Exons 5-8 harbor mutations most frequently, mainly of the missense type, resulting in accumulation of the p53 protein. The importance of these alterations as prognostic factors, are issues of controversy. MATERIAL AND METHODS: Thirty-four patients suffering from stage I tongue carcinoma had been treated with a local surgical excision of the tumor. Seventeen patients had developed a local recurrence in the tongue or cervical (regional) metastases while 17 patients, matched for age and gender to the former group, had no recurring disease within follow-up. Protein p53 was detected through immunohistochemical (IHC) analysis using antibody CM1. Exons 5-8 of the TP53 gene were amplified through the Polymerase Chain Reaction (PCR). The presence of mutations analyzed by CDGE (Constant Denaturant Gel Electrophoresis) and detected mutations were subjected to sequencing. RESULTS: 20 out of 34 tumors (59%) showed mutated TP53, 18 tumors were IHC p53 positive, but the correlation between CDGE and IHC was only 56%. Sequencing of the gene was possible in 8 cases. CONCLUSIONS: Neither the presence of mutations nor immunostaining had any impact on the risk of recurrence expressed as life-table analysis of time to recurrence.


Assuntos
Carcinoma de Células Escamosas/genética , Genes p53 , Mutação de Sentido Incorreto , Neoplasias da Língua/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Eletroforese em Gel de Poliacrilamida , Éxons , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Recidiva , Fatores de Risco , Fatores de Tempo , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/cirurgia , Proteína Supressora de Tumor p53/metabolismo
17.
Anticancer Res ; 21(1B): 509-12, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11299796

RESUMO

Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a histopathologically well-defined condition. There is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed immunohistochemical staining with a polyclonal antibody against recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS lesions which progressed to invasive cancer, within a follow-up time of 5 years, were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not progress were positive (37%) (p < 0.01). Our data showed that a positive laminin-5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Moléculas de Adesão Celular/análise , Neoplasias Laríngeas/patologia , Invasividade Neoplásica/diagnóstico , Proteínas de Neoplasias/análise , Adulto , Idoso , Animais , Carcinoma in Situ/química , Carcinoma de Células Escamosas/química , Administração de Caso , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/química , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Prognóstico , Subunidades Proteicas , Coelhos , Proteínas Recombinantes de Fusão/imunologia , Risco , Calinina
18.
Anticancer Res ; 14(5B): 2259-66, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7840533

RESUMO

In order to determine whether or not the p53 gene is involved in the malignant transformation of the head and neck carcinoma HNSCC, we have analyzed archival specimens from 527 primary head and neck lesions and 27 corresponding lymph node metastases. Nuclear p53 protein was present in 107 of 190 (56%) dysplasias, 61 of 102 (60%) carcinoma in situ (CIS), and 262 of 493 (53%) carcinomas. The p53 score did not increase significantly with progression of these lesions from dysplasia to CIS and to carcinoma. All 357 normal samples of head and neck tissues were negative. The majority of the 172 sets of premalignant and malignant lesions displayed concordant p53 staining patterns. The staining was incongruous in only six cases. The p53 staining results were congruent in all 27 pairs of primary and metastatic (lymph nodes) tumors. These data strongly suggest that p53 protein could be altered in a very early phase of the head and neck tumorigenesis and is maintained during tumor progression and metastatic spread. Mutations in p53 were examined in 11 cases that exhibited high levels of p53 protein as detected by immunohistochemistry using PAb 1801 MAb. Mutation analysis was performed by direct sequencing of the PCR amplification products of exons 5 through 8, which contain greater than 90% of p53 mutations found in tumors. Three of 11 HNSCC had mutations at codon 130 (C to A), 193 (A to T), 283 (G to C), respectively. No mutations were found in the other 8 samples within the regions examined. However, they may have mutations in unsequenced regions of p53 or may have wild type protein that accumulates for other reasons.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Lesões Pré-Cancerosas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma de Células Escamosas/metabolismo , Feminino , Genes p53 , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação Puntual , Lesões Pré-Cancerosas/metabolismo , Proteína Supressora de Tumor p53/biossíntese
19.
Anticancer Res ; 14(3B): 1281-5, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8067697

RESUMO

Biopsies from 34 patients with cancer of the head, neck or esophagus, 2 laryngeal papillomas, and 2 normal tonsils were analysed for human papillomavirus (HPV), Epstein Barr virus (EBV) genomes and mutated or elevated levels of p53. In 4 biopsies p53 was also analysed by DNA sequencing. HPV type 31 was found in one laryngeal cancer with normal p53 and HPV type 16 in two tonsil cancers with aberrant p53 expression. EBV was detected by PCR in 11 biopsies, but in situ hybridisation and immunohistochemistry, did not confirm this finding. Aberrant p53 expression was observed in approximately half of the tumours. These results support the involvement of both aberrant p53 expression and HPV in the aetiology of squamous cell carcinoma of the head and neck.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Papillomaviridae/isolamento & purificação , Proteína Supressora de Tumor p53/análise , Sequência de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/virologia , Seguimentos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase
20.
Arch Otolaryngol Head Neck Surg ; 122(8): 833-6, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8703384

RESUMO

BACKGROUND: Pseudomonas aeruginosa rarely affects the epithelium in healthy persons except for the external ear canal, raising the possibility that P aeruginosa in otitis externa is a specific variety that displays particular characteristics. DESIGN: A cohort study was designed to outline distinct characteristics of P aeruginosa in otitis externa compared with P aeruginosa in other infections. The study period was October 1, 1994, to March 27, 1995. PATIENTS: Isolates of P aeruginosa from nonhospitalized patients were collected at the bacteriological laboratory at Karolinska Hospital, Stockholm, Sweden; there were 53 strains of P aeruginosa isolated from otitis externa and 59 strains of P aeruginosa from varicose ulcers and urinary tract infections. METHODS: Pseudomonas aeruginosa was characterized by pigmentation, growth habits, production of mucoid, and biochemical characteristics. RESULTS: Pseudomonas aeruginosa in otitis externa produced less pyocyanin and less urease and exhibited no mucoid-producing strains. CONCLUSIONS: Pseudomonas aeruginosa in otitis externa displayed fewer of the usual biochemical features of the species than did the strains isolated from other infections. Some of these features, such as the production of pyocyanin, are influenced by nutritional factors; strains found in otitis externa probably represent the type of strains present in the natural habitat in water, as opposed to the strains that have adapted to the environment of other human infections. Increased knowledge of the characteristics of the strains found in otitis externa is important in understanding the pathogenesis of the disease and why P aeruginosa is the dominant infectious agent in otitis externa.


Assuntos
Oligopeptídeos , Otite Externa/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/classificação , Humanos , Testes de Sensibilidade Microbiana , Pigmentos Biológicos/biossíntese , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , Piocianina/biossíntese , Infecções Urinárias/microbiologia , Úlcera Varicosa/microbiologia
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