1,721,022 research outputs found
p53 overexpression and mutation, chemoresistance and patient survival in oral and maxillofacial squamous carcinoma
No full textIn this study has been investigated the status of p53 in oral and maxillofacial squamous cell carcinoma and its relation to chemosensitivity and patient survival.
The AA have considered 15 patients with advanced oral and maxillofacial squamous cell carcinoma (G2 grade) who received chenotherapy prior to surgery (3 cycles CDDP/5-FU: 30 mg/m2 i.v., days 2,3,4; 1000 mg/m2 i.v. continous infusion for 5 days). P53 genetic analysis was available from deparaffin histologic specimens and performed by DNA extraction and PCR (polymerase chain reaction) methods. P53 staining using polyclonal antibody was also carried out. P53 mutations from a p53-overexpressing tumor were found in 3 of 15 patients. At postchemotherapy restaging the AA found 2 progressions and 2 stable diseases. In the 12 patients with wild-type p53 were: 4 objective responses and 55% partial response (PR) in 1,60% PR in 1,65% PR in 1,70% PR in 1,75% PR in 2, and 90% PR in 2. Patient survival, with median follow-up, tended to be poor when p53 was altered (p<0.05)
P53 and H-RAS immunohistochemical and genetic investigation in maxillofacial tumours
No full textThe AA carried out a immunohistochemical and genetic research on the tumor suppressor protein p53 and H-RAS oncogene in oromaxillofacial neoplasms. The purpose was to verify, by genetic control, the possibility of find the eventual correlations between histopathological overexpression degree (per cent) of the oncogenes and chemoresistance. The study was carried out on 15 cases of squamous cell carcinomas of the oromaxillofacial region, in advanced stage, with equal histopathological grading (G2), underwent neoadjuvant chemotherapy according to the following protocol: Cis-diamonodichloroplatinum (CDDP, 20 mg/mq i.v. days 1,2,3,4,5) and 5Fluorouracil (5-FU 1000mg/mq continous infusion, volumetric pump 2 ml/hour, for five days). The restaging was carried out after three cycles of chemotherapy to value the clinical response. The p53 immunohistochemical study (clone DO-7) showed a pathological overexpression in 9/15 cases; whwreas, the genetic control (PCR method, wild DNA) showed mutations in 5/15 cases, corresponding to, respectively, 95%, 80%, 70% and 95%. The H-RAS immunohistochemical study (AB-1) (clone 235-1.7.1) showed a pathological overexpression in 12/15 cases; the genetic control showed mutations in 9/15 cases, corresponding to, respectively, 90%, 35%, 10%, 20%, 77%, 90%, 85%, 25%, 75%. The response to the neoadjuvant chemotherapic treatment was as follows: 2 partial response (PR) (90%) in 1 K of the cheek (p53 and H-RAS: imm -, gen -) and in 1 K of the soft palate (p53 and H-RAS: imm -, gen -), with global survival (GS) at diagnosis of, respectively, 18 and 15 months. 1 PR (75%) (p53: imm - , gen -; H-Ras: imm 10%, gen -) and 4 PR (55%) (1 – p53: imm 25%, gen -; H-RAS: imm 20%, gen MUT. 2- p53: imm 45%, gen -; H-RAS: imm 90%, gen MUT. 3- p53: imm -, gen -; H-RAS: imm -, gen -. 4- p53: imm -, gen -, H-RAS: imm 30%, gen -) in 5 K of the gum, with GS of, respectively, 10,6,8,9 and 8 months. 2 objective improvements (OI) in, respectively, 1 K of the floor of the mouth (p53: imm 15%,
gen -; H-RAS: imm 37%, gen -) and 1 K of the gum (p53: imm -, gen -; H-RAS: imm 10%, gen MUT), with GS of, respectively, 5 and 6 months. 3 Stability of disease (S) in 2 K of the tongue (1- p53: imm 70%, gen MUT;
H-RAS: imm 35%, gen MUT. 2- p53: imm 25%, gen -; H-RAS: imm 25%, gen MUT) and 1 K of the gum (p53: imm 45%, gen MUT; H-RAS: imm 85%, gen MUT), with GS of, respectively, 10,7 and 7 months. 3 Progressione (P) in 2 K of the floor of the mouth (1- p53: imm 95%, gen MUT; H-RAS: imm 90%, gen MUT. 2- p53: imm 80%, gen MUT; H-RAS: imm 75%, gen MUT) and in 1 K of the cheek (p53: imm 95%, gen MUT; H-RAS: imm 77%, gen MUT), with GS of, respectively, 8,8 and 6 months.
The study showed a degree of correlation between genetic analysis and immunohistochemical investigation of, respectively, 73.3% of cases for the p53 and of 80% of cases for the H-RAS (Chi-Square Test: p = 0.3089)
Mutazioni della p53 e chemioresistenza nei carcinomi squamosi oro-maxillo-facciali. 1. Ruolo della p53 nel controllo del ciclo cellulare e nel modulare l'azione dei composti chemioterapici
No full textUn ruolo cruciale nel controllo della omeostasi cellulare e, di conseguenza, nel processo di induzione neoplastica vienne riconosciuto alla p53 (“tumor suppressor gene”), un antioncogene trovato mutato con una incidenza significativamente elevata nella maggior parte dei tumori dell’organismo. Nelle neoplasie oro-maxillo-facciali le percentuali di mutazione della p53 variano dal 4% al 60%. Studi in vitro su tumori colo-rettali, della mammella, del polmone, dell’ovaio, del testicolo, della vescica, e nelle leucoblastosi, hanno messo in evidenza una correlazione tra alterazioni della p53 e chemioresistenza. La relazione funzionale tra la p53 e l’azione di alcuni composti chemioterapici, quelli che danneggiano direttamente il DNA, risiede nell’apoptosi, un meccanismo fisiologico attivato dalla p53 a scopo omeostatico (regolazione della crescita cellulare) e nello stesso tempo necessario per l’azione dei suddetti chemioterapici (l’apoptosi è un processo irreversibile
che culmina con la morte cellulare). Se nelle cellule del tessuto neoplastico la p53 è mutata l’apoptosi non viene attivata e ciò può ripercuotersi negativamente sulla citoriduzione ottenibile con la chemioterapia.
Tali acquisizioni hanno portato a prime applicazioni in campo clinico. Nei tumori della mammella la p53 viene già utilizzata come marker di chemioresponsività, indirizzando il protocollo chemioterapico, nei casi di mutazione, verso l’utilizzo di composti alternativi (es. il Taxolo), che hanno una azione svincolata dal sistema dell p53. In tumori del polmone si è arrivati, addirittura, ad introdurre la molecola “wild-type” della p53 nelle cellule neoplastiche con l’oncogene mutato, utilizzando tecniche di transfezione con retrovirus, ottenendo una migliore risposta clinica al trattamento chemioterapico.
Nelle neoplasie oro-maxillo-facciali, come noto, il trattamento cardine è quello chirurgico.
Gli AA sottolineano come nelle forme tumorali particolarmente avanzate esso, come noto, sia inserito in un protocollo multimodale in cui, con precise indicazioni, ha un importante ruolo la chemioterapia neoadiuvante. La possibilità, quindi, che lo studio genetico offre di valutare preventivamente lo “status” della p53, può costituire, a loro avviso, unitamente ai ben noti parametri di valutazione prognostica, un elemento specifico di screening, indicativo della chemioresponsività del tessuto neoplastico, con indubbio vantaggio ai fini della impostazione terapeutica e, in particolare, della programmazione chirurgica
Immunohistochemical study and molecular assay in oral cancer: a cohort analysis of prognostic factors.
No full textAIM - The AA carried out an immunohistochemical and genetic research on p53 tumor suppressor gene and H-ras oncogene in maxillofacial tumors to evaluate the p53 and H-ras status, response to induction chemotherapy, and global survival, keeping up a study performed from many years.
METHODS - 25 consecutive cases of squamous cell carcinomas with metastatic nodes were selected on the basis of homogeneous grading (G2). The patients underwent induction chemotherapy (CDDP/5FU), restaging, surgery, and adjuvant radiotherapy. Monoclonal AB, and Dna extration and PCR amplification were utilized, respectively, for immunohistochemical and genetic analysis of p53 and H-ras.
Differences between proportions of contingency tables were assessed by the Fisher Exact Test; correlation analysis was done using Spearmen Correlation Coefficient. Univariate (product limit) and multivariate (proporzional hazards model) methods were used to estimate prognostic variables and related death risk.
RESULTS - The data show a strong association then between H-RAS overexpression and H-RAS genetic mutations (pFisher =0.000064) that between P53 overexpression and P53 genetic mutations (pFisher =0.000203). A significant inverse correlation was found between P53 overexpression and chemotherapy response (r= -0.892, p= 0.0001).
The cumulative survival of the entire cohort at 28 mounths of follow-up is 28.58% (standard error=10.24%).
Percentage of p53 Monoclonal AB linked > 45% is prognostic variable for death risk with relative risk of 8.89 (95% c.i. 2.48-31.90).
CONCLUSIONS - These data show that immunohistochemical study should be inserted in the staging system of tumor mostly in the advanced lesions which need multimodality of treatment. Oncogenetic pattern supplies important elements for diagnostic and prognostic evaluation, besides the classical factors of screening, and it may work together in better therapeutic planning
Oro-maxillofacial tumours: immunohistochemical study, genetical analisis and response to the chemotherapic treatment
No full textOral cancer. Evaluation of prognostic factors by a cohort analysis of immunoistochemical and genetic P53/HRAS data in advanced cases.
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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