Biomedical subjects

Francesco Carinci

Publications and source records attributed to Francesco Carinci.

At least 19 recordsLinked to original sources

PubMed2007

Wide-diameter implants: analysis of clinical outcome of 304 fixtures.

BACKGROUND: In the last decade, the use of wide-diameter implants (WDIs; diameter >3.75 mm) has increased. Although good clinical outcomes have been reported in recent literature, there are few reports on this topic. Thus, we planned a retrospective study on a large series of WDIs to evaluate the clinical outcome. METHODS: From October of 1996 to December of 2004, 205 patients were operated on, and 304 WDIs were inserted. The mean postloading follow-up was 30 months. Implant diameter and length ranged from 5.0 to 6.5 mm and from 8.0 to 15 mm, respectively. Because only five of 304 implants were lost (i.e., a survival rate of 98.4%) and no statistical differences were detected among the studied variables, no or reduced crestal bone resorption (CBR) was considered an indicator of success to evaluate the effect of several host-, surgery-, and implant-related factors. A general linear model (GLM) was performed to detect variables that were associated statistically with CBR. RESULTS: Only five of 304 WDIs were lost, and no differences were detected among the studied variables. On the contrary, the GLM showed that distal teeth (i.e., premolars and molars), small implant diameter (i.e., 5.0 and 5.5 mm), and short implant length (i.e., <13 mm) correlated with a statistically significant lower CBR. CONCLUSION: The use of WDIs is a viable treatment option, and it may provide benefits in posterior regions for long-term maintenance of various implant-supported prosthetic rehabilitations.

Adolescent↗

PubMed2006

TGFbeta3 expression in non-syndromic orofacial clefts.

BACKGROUND: Genetic studies have demonstrated that non-syndromic cleft is composed of two separate entities - cleft palate only (CPO) and cleft of lip, alveolus with or without cleft palate (CL+/-P) -, both have a heterogeneous genetic background and environmental factors contribute to the onset of these malformations. Previous studies have shown that TGFbeta3 could be involved in these diseases, but no conclusive results have been reached. PURPOSE: In order to detect if TGFbeta3 has a role in cleft diseases, a series of non-syndromic cleft patients and controls are analyzed for TGFbeta3 protein expression. MATERIAL AND METHODS: Forty-three non-syndromic cleft patients and 21 unaffected subjects were involved in this study. Paraffin-embedded specimens were matched with the TGFbeta3 antibody and then scanned with a computerized image analyzer. TGFbeta3 was found to be absent (less than 10%), moderate (from 10% to 30%) and highly expressed (higher than 30%) in epithelium (EP), minor palatal salivary gland (GL) and fibres of elevator palati muscle (MU). Data was statistically analyzed with a Kruskal-Wallis test. RESULTS: Only GL and EP have a statistically significant lower expression in non-syndromic cleft compared to unaffected subjects. A subsequent comparison between CL+/-P and CPO groups demonstrates a statistically significant difference only for GL, with a lower expression in GL of CPO patients. CONCLUSIONS: TGFbeta3 is decreasingly expressed in GL of unaffected CL+/-P and CPO patients and thus further strength is given to a pathogenetic role of TGFbeta3 in the onset of clefts.

Case-Control Studies↗

PubMed2006

Effect of c-Met expression on survival in head and neck squamous cell carcinoma.

The proto-oncogene c-Met has been suggested to be associated with progression of squamous cell carcinoma of the head and neck. The aims of the present study were to assess the prevalence of c-Met expression in oral squamous cell carcinoma (OSCC) and to verify whether c-Met can be considered a marker of prognosis in these patients. In a retrospective study, a cohort of 84 OSCC patients was investigated for c-Met expression and its cellular localization by immunohistochemistry. After grouping for c-Met expression, OSCC patients were statistically analyzed for the variables age, gender, histological grading, tumor node metastasis, staging and overall survival rate. Univariate and multivariate statistics were used for data analysis. Sixty-nine cases (82.2%) of OSCC showed immunopositivity, with a mainly membranous expression and scattered areas also showing a cytoplasmic localization, whereas 15 cases (17.8%) did not show c-Met. No statistical association was found between c-Met expression and any variables considered at baseline, apart from the higher number of c-Met positivity in females (p = 0.026). Among positive tumors, well-differentiated areas showed low or absent cytoplasmic expression, while low-differentiated areas showed both membranous and cytoplasmic positivity. In terms of prognostic significance, c-Met expression was found to have an independent association with a poorer overall survival rate (p = 0.036). On the basis of these results, it is possible to suggest c-Met as an early marker of poor prognosis, a hallmark of aggressive biological behavior in OSCC, suggested to be useful in identifying cases of OSCC before the relapse.

Adolescent↗

PubMed2006

Study of four genes belonging to the folate pathway: transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate.

Cleft lip with or without cleft palate (CL/P) is the most common inborn craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although CL/P has a complex and poorly understood etiology, increasing evidence of folate pathway involvement has been collected. So far, only the MTHFR gene has been extensively investigated as a risk factor for CL/P, while little has been done to test genetic variations in the folate biosynthetic pathways that may influence the infant's susceptibility to these birth defects. To date, this paper presents the first attempt to verify the involvement of four genes belonging to the folate pathway in nonsyndromic cleft onset. We used a case-parent triad design to test for linkage disequilibrium in the case of seven SNPs mapping on four different genes: transcobalamin 1 and 2 (TCN1 and TCN2), methionine synthase (MTR), and MTR reductase (MTRR). Our finding suggests that TCN2 is involved in causing CL/P. Indeed, significant overtransmission of the C allele was observed at the polymorphism c.776C>G (p.Pro259Arg) to the affected offspring (P=0.01). Results obtained with additional TCN2 polymorphisms suggest that c.776C>G may be functionally related to CL/P. However, because conflicting data exist with regard to the effect of the polymorphism in transcobalamin 2 function or in perturbing plasma levels of key molecules in the folate pathway, further investigation is warranted to confirm our data.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2006

Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair.

It is not known whether cells derived from stem cells retain their differentiation and morpho-functional properties after long-term cryopreservation. This information is of importance to evaluate their potential for long-term storage with a view to subsequent use in therapy. Here, we describe the morpho-functional properties of dental pulp stem cells (SBP-DPSCs), and of their differentiated osteoblasts, recovered after long-term cryopreservation. After storage for 2 years, we found that stem cells are still capable of differentiation, and that their differentiated cytotypes proliferate and produce woven bone tissue. In addition, cells still express all their respective surface antigens, confirming cellular integrity. In particular, SBP-DPSCs differentiated into pre-osteoblasts, showing diffuse positivity for ALP, BAP, RUNX-2, and calcein. Recovered osteoblasts expressed bone-specific markers and were easily recognizable ultrastructurally, with no alterations observed at this level. In addition, after in vivo transplantation, woven bone converted into a 3D lamellar bone type. Therefore, dental pulp stem cells and their osteoblast-derived cells can be long-term cryopreserved and may prove to be attractive for clinical applications.

Adult↗

PubMed2006

In vitro bone production using stem cells derived from human dental pulp.

To harvest bone for autologous grafting is a daily problem encountered by craniofacial and oral surgeons. Stem cells derived from human dental pulp are able to differentiate in osteoblasts and are a potential source of autologous bone produced in vitro. The authors describe their preliminary results in this new field with its potential application in craniomaxillofacial surgery. Dental pulp was gently extracted from 34 human permanent teeth (all third molars) of patients 19 to 37 years of age. After they were digested, the cells were selected using a cytometer for c-kit, STRO-1, CD34, CD45, and then for CD44 and RUNX-2. This study, made on a considerable number of cases, provided evidence that dental pulp is extremely rich in stem cells, which were c-kit+/CD34+/STRO-1+/CD45-, capable of differentiation toward several stromal-derived differentiated cells and mainly osteoblasts. These findings, supported by the large number of cases, are of great interest for tissue regeneration, tissue-based clinical therapies, and transplantation.

Adolescent↗

PubMed2006

Orbital fractures: a new classification and staging of 190 patients.

The orbit is located in the middle third of the face, composed of several bones and surrounded by complex anatomic structures so that orbital fractures (OF) often involve other parts of the face. A staging system for classifying OF is of paramount importance in order to exchange information between trauma centers. Several classifications have been proposed for describing OF but they have not a single method applicable to the whole orbit. Here, a classification for OF that can be summarized with four abbreviations is proposed. Four letters define the localization (F = frontal, N = nasal, M = maxillary and Z = zygomatic bone fracture), two acronyms describe fragment shift (in = blow-in or out = blow-out), four numbers define ocular movement impairment (1 = superior, 2 = internal, 3 = inferior, and 4 = external extrinsic muscular deficit) and two acronyms describe eye position (EX = exophthalmos and ENO = enophthalmos). To evaluate the suitability of the proposed classification a retrospective study on a series of 190 OFs is performed. Age, gender, new stage, clinical diagnosis at admission, type of surgery, and need for graft for orbital reconstruction are considered. A good correlation between the proposed classification and the studied variables is detected. In conclusion, the proposed classification is a simply and precise method to stage OF. It can summarize OF and be used in the daily practice. However, it is our belief that a multi-center study should be performed before the effectiveness of the proposed classification can be clearly stated.

Adolescent↗

PubMed2006

Calvarial bone grafts and temporalis muscle flap for midfacial reconstruction after maxillary tumor resection: a long-term retrospective evaluation of 17 patients.

Midfacial reconstruction after radical oncological resection is a challenging endeavor and several options can be employed: prosthethic devices, pedicled flaps (with or without the aid of autologous or alloplastic grafts), and microvascular flaps. Each technique has specific indications, advantages and disadvantages. The use of traditional surgical reconstructive procedures seems to be shifted nowadays by microvascular free flaps. Nevertheless, in our experience the myofascial temporalis flap associated with free calvarial bone grafts demonstrate to be a safe and versatile option in primary midfacial reconstruction. From this point of view the authors have developed a technique for one-stage reconstruction of the orbito-maxillary skeleton and soft tissues and without the use of microsurgical flaps; this surgical procedure can be used only on patients for whom a resection of the cutaneous tissues and exenteratio orbitae are not necessary. The aims of this paper is to describe the surgical technique and to show a retrospective analysis on 17 patients which underwent midfacial radical resection and immediate reconstruction with calvarial bone grafts and temporalis muscle flap along 15 years.

Adult↗

PubMed2006

Genetic effects of Medpor on osteoblast-like cells.

Porous polyethylene (PP or Medpor) is an alloplastic material used worldwide for craniofacial reconstruction. Although several clinical studies are available, there is a lack as regard the genetic effects. Because PP is always fixed on bone and the mechanism by which PP acts on osteoblasts is unknown, we therefore attempted to address this question by using microarray techniques to identify genes that are differently regulated in osteoblasts exposed to PP. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cell lines (i.e. MG-63) cultured on PP several genes where expression was differentially regulated. The differentially expressed genes cover a broad range of functional activities: 1) signal transduction, 2) transcription, 3) translation, 4) cell cycle regulation, 5) vesicular transport, and 6) production of cytoskeletal elements, cell-adhesion molecules and extracellular matrix components. The data reported are, to our knowledge, the first genetic portrait of osteoblast-like cells cultured on PP. They are relevant to better understanding of the molecular mechanism of bone-PP interaction and as a model for comparing other materials used for bone reconstruction.

Bone Substitutes↗

PubMed2006

Parallel screw cylinder implants: comparative analysis between immediate loading and two-stage healing of 1,005 dental implants with a 2-year follow up.

BACKGROUND: Recently, several authors have focused on the possibility of an immediate functional loading of dental implants to minimize the delay between surgical and prosthetic phases. PURPOSE: The aim of this study was a reevaluation of the XiVE dental implant (Dentsply-Friadent, Mannheim, Germany) with: (1) a longer follow-up period; (2) a higher number of fixture; and (3) a proper statistical method. MATERIALS AND METHODS: In July 2001 and December 2002, 371 patients (180 males and 191 females; ages ranging from 17 to 83; mean age, 53 years) were consecutively enrolled in this study. In 371 patients, a total of 1,005 XiVE dental implants were distributed as follows: 484 immediately loaded implants (test group) were inserted in 130 patients, whereas 521 unloaded implants were inserted in 241 patients (control group). RESULTS: The implant survival was 98.7 and 99.4% in immediate loading and control group, respectively. Univariate analysis showed no statistically significant difference between the two groups. CONCLUSION: In a previous report, we showed that immediate loading offered a predictable and reliable procedure also for XiVE implants, at least in the short period. In this study, we confirmed the results of the previous study and added information regarding the survival rate and marginal bone level stability with a 2-year follow up.

Adolescent↗

PubMed2006

Five-year outcome of 111 immediate nonfunctional single restorations.

Immediate loading is a surgical-prosthetic procedure extensively used in implant dentistry. Despite its frequent use, minimal data are available on the long-term clinical success rate of immediate functional loading (IFL) and immediate nonfunctional loading (INFL) of implants. The aim of this study was to evaluate the long-term survival and bone loss of immediate nonfunctional single implant restorations in a group of patients that were monitored for 5 years. One hundred and eleven patients (41.4% men) with a median age of 40 years were included in this study. A total of 111 implants were placed. All implants were placed with a minimum insertion torque of 25 Ncm. A temporary restoration was relined with acrylic resin, trimmed, polished, and cemented or screw-retained 1 to 2 hours later. Occlusal contact was avoided in centric and lateral excursions. After provisional crown delivery, a periapical radiograph was performed by means of a customized Rinn holder device. Data were analyzed by means of Kaplan-Meier and life-table algorithms. Stratification of implant survival was performed for the available variables of interest, and comparisons were analyzed using a log-rank test. Investigated parameters were time of implant placement, bone quality, implant site, implant diameter and length, and type of implant surface enhancement. The parameters for overall success rate were defined by bone resorption <1.5 mm after the first year of loading and <0.2 mm thereafter. During the 5-year follow-up period, a survival rate of 95.5% was observed. All failures occurred within 4 months of implant loading. There were statistically significant differences regarding healed vs post-extraction implant sites (100% and 92.5%, respectively, P = .05) and type of bone (D1 vs D4 yielded 100% and 95.5%, respectively, P <.05). No differences were detected for: (1) site (100% for mandible and 94.63% for maxilla, P =-.319); (2) implant diameter (survival rates of 97.26% for <4.5-mm diameter and 92.11% for >4.5mm diameter, P = .206); (3) implant lengths (survival rates of 96.97% for implants >13 mm and 94.87% for implants <13 mm, P =.624); and (4) type of implant surface enhancement (survival rates of 94.03% for 67 cases of grit-blasted and acid-etched surfaces and a failure rate of 4 out of 5, and 94.12% for 17 cases of hydroxyapatite (HA)-coated surfaces with only 1 failure). The success rate (defined as bone resorption >1.5 mm after the first year of loading and >0.2 mm thereafter) was 97.2%. Immediate nonocclusal loading of single implants is a reliable surgical-prosthetic procedure with a low rate of implant loss and a low quantity of peri-implant bone loss over time.

Adolescent↗

PubMed2005

Delaire's cheilorhinoplasty: unilateral cleft aesthetic outcome scored according to the EUROCLEFT guidelines.

OBJECTIVE: The aim of our study is to evaluate, in accordance with EUROCLEFT guidelines, the aesthetics of nasolabial area in a sample of complete unilateral cleft of lip and palate patients (UCLP), after surgical correction with Delaire' technique. METHODS: Twenty-two UCLP patients (16 males and 6 females, 9 right and 13 left side clefts) were enrolled in this retrospective study. Patients were operated at 7 (mean value) months of age by a single surgeon. Frontal and sub-mental photos for each baby were recorded at 8.5 (mean value) years of age, and evaluated twice, by three independent maxillofacial surgeons. A five-point scale (EUROCLEFT guidelines) was used. Nonparametric analysis (Kruskal-Wallis test) was applied to detect differences in medians obtained in studied groups. RESULTS: Kruskal-Wallis test showed no statistical significant differences among evaluations of three surgeons and between the first and the second evaluation of the same surgeon. The global appearance of the upper lip and nose was scored with a mean value of 2 (i.e. good). The sample was then divided into two subgroups, according with patient' age; the aesthetics and the symmetry of the nose resulted better in elder patients (i.e. subgroup A, mean period of observation=10.2 years), whereas upper lip achieved better results in younger patients (i.e. subgroup B, mean period of observation=4.9 years). CONCLUSIONS: EUROCLEFT guidelines are a useful method to evaluate--aesthetically and over time--cleft lip and palate patients, treated with a single surgical procedure. We hypothesize that Delaire technique could progressively improve aesthetics and symmetry of the nose, throughout the growth of the patient.

Child↗

PubMed2005

Genetic effects of anorganic bovine bone (Bio-Oss) on osteoblast-like MG63 cells.

Bio-Oss (Geistlich, Wolhusen, Switzerland) is composed by anorganic bovine bone and is widely used in several bone regeneration procedures in oral surgery. How this biomaterial alters osteoblast gene expression to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to identify genes that are differentially regulated in osteoblasts exposed to Bio-Oss. By using DNA microarrays containing 20,000 genes, we identified in osteoblast-like cells line (MG-63) cultured with Bio-Oss several genes which expression was significantly up- and down-regulated. The differentially expressed genes cover a broad range of functional activities: (a) signaling transduction, (b) transcription, (c) cell cycle regulation, (d) vesicular transport, (e) apoptosis, and (f) immunity. These results could explain the reported bioaffinity of Bio-Oss to host animals, its biological affinity to osteogenic cells and its capability to stimulate osteoblastic differentiation. The data reported are, to our knowledge, the first genetic portrait of Bio-Oss effects. They can be relevant to our improved understanding of the molecular mechanism underlying bone regenerative procedures and as a model for comparing other materials with similar clinical effects.

Animals↗

PubMed2005

P-cadherin expression and survival rate in oral squamous cell carcinoma: an immunohistochemical study.

BACKGROUND: P-cadherin (P-cad) is a transmembrane molecule involved in the cell-cell adhesion and similar to E-cadherin (E-cad), but less investigated in oncology, especially in in vivo studies. Aims of the present study were to assess the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC) and to verify whether P-cad can be considered a marker of prognosis in patients with OSCC. METHODS: In a retrospective study, a cohort of 67 OSCC patients was investigated for P-cad expression and its cellular localization by immunohistochemistry; some respective healthy margins of resection were similarly investigated as standard controls. After grouping for P-cad expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, Staging, and overall survival rate. Univariate and multivariate analyses were performed. RESULTS: 37 cases (55.2%) of OSCC showed membranous/cytoplasmic positivity for P-cad, whereas 30 (44.8 %) were negative. Although with some differences in membranous vs cytoplasmic localization of P-cad in OSCC with different G, no statistical association was found between P-cad expression and any variables considered at baseline. In terms of prognostic significance, P-cad non expression was found to have an independent association with poorer overall survival rate than P-cad expressing group (P = 0.056); moreover, among P-cad +ve patients the best prognosis was for those OSCC with membranous (P < 0.0001) than those with cytoplasmic P-cad expression. CONCLUSION: On the basis of these results, it is possible to suggest P-cad as an early marker of poor prognosis. The abnormal or lack of P-cad expression could constitute an hallmark of aggressive biological behavior in OSCC.

Adolescent↗

PubMed2005

A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB).

UNLABELLED: Stem cells, derived from human adult dental pulp of healthy subjects 30-45 years of age, were cultured, and cells were selected using a FACSorter. A new c-kit+/CD34+/CD45- cell population of stromal bone producing cells (SBP/DPSCs) was selected, expanded, and cultured. These SBP/DPSCs are highly clonogenic and, in culture, differentiate into osteoblast precursors (CD44+/RUNX-2+), still capable of self-renewing, and then in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue, which is markedly positive for several bone antibodies. This tissue constitute an ideal source of osteoblasts and mineralized tissue for bone regeneration. In fact, after in vivo transplantation into immunocompromised rats, LAB formed lamellar bone-containing osteocytes. INTRODUCTION: Recently it has been reported that human dental pulp stem cells (DPSCs) are detectable, in humans, only up to the age of 30 years and that they are able to produce in vitro only sporadic calcified nodules and to form, after transplantation in vivo, a mineralized tissue. MATERIALS AND METHODS: Stem cells, derived from human adult dental pulp of healthy subjects 30-45 years of age, were cultured, and cells were selected using a FACSorter. Light microscope, histochemistry, immunofluorescence, and RT-PCR analyses were performed to study both stem and differentiating cells. RESULTS AND CONCLUSIONS: A new c-kit+/CD34+/CD45- cell population of stromal bone producing cells (SBP/DPSCs) has been selected by FACSorting, expanded, and cultured. These SBP/DPSCs are highly clonogenic and, in culture, differentiate into osteoblast precursors (CD44+/RUNX-2+), still capable of self-renewing, and in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue. This new-formed tissue is markedly positive for several antibodies for bone, including osteonectin, bone sialoprotein, osteocalcin, fibronectin, collagen III, and bone alkaline phosphatase (BALP). Cells producing LAB can be stored at -80 degrees C for a long period of time and are an extraordinary source of osteoblasts and mineralized fibrous bone tissue. In this study, we also showed that, in aged humans, stem cells can be detected from their pulps. The produced LAB is a fibrous bone tissue resembling the human bone during mineralization, with an external layer formed by osteoblasts markedly positive for osteocalcin. This newly formed tissue constitute an ideal source of osteoblasts and mineralized tissue for bone regeneration. In fact, after in vivo transplantation into immunocompromised rats, LAB formed lamellar bone containing osteocytes.

Adult↗

PubMed2005

Study of folate receptor genes in nonsyndromic familial and sporadic cleft lip with or without cleft palate cases.

Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P.

Carrier Proteins↗

PubMed2005

Effect of Vitamin C on pre-osteoblast gene expression.

Ascorbic acid (AA), also known as Vitamin C, is a cofactor required for the function of several hydroxylases. It is not synthesised in humans and has to be provided by diet. Its absence is responsible for scurvy, a condition related to the defective synthesis of collagen by the reduced function of prolylhydroxylase. AA is also a risk factor for periodontal disease. Recently, it has been shown that AA induces embryonic stem cells to differentiate into osteoblasts. The mechanism by which AA sustains pre-osteoblast proliferation and commitment is mediated through the synthesis of collagen type I, interaction with alpha2- and beta1-integrin, activation of the mitogen-activated protein kinase pathway, and phosphorylation of osteoblast-specific transcription factors. However, the multifunctional role of AA is not fully elucidated. MC3T3-E1 mouse calvaria-derived cell line is a well-defined in vitro model of pre-osteoblast differentiation, and AA is essential for the proliferation and differentiation of MC3T3-E1. By using DNA micro-arrays containing 15,000 genes, we identified several genes in MC3T3-E1 cultured with AA for 24h whose expression was significantly up or downregulated. The differentially expressed genes covered a broad range of functional activities: (1) cell growth; (2) metabolism; (3) morphogenesis; (4) cell death; (5) cell communication. The data reported are, to our knowledge, the first genetic portrait of early stage stimulation of pre-osteoblasts by AA, and may be relevant to better understand the molecular mechanism of pre-osteoblast proliferation and commitment. Elucidation of the molecular mechanism has important clinical implications because it may facilitate the correct use of AA to accelerate bone regeneration.

3T3 Cells↗

PubMed2005

Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma.

BACKGROUND: To detect epigenetic changes in head and neck squamous cell carcinoma (HNSCC) and between metastatic and nonmetastatic tumors, we performed a systematic phosphorylation screening on different protein kinases. METHODS: The phosphorylation levels of the serine-threonine kinase Akt, of mitogen-activated protein kinase (MAPK), and of protein kinase C (PKC) beta and epsilon were measured in a series of 94 biopsy specimens, corresponding to 47 HNSCCs and paired controls taken from clinically uninvolved tissue of the same patients. RESULTS: Akt and MAPK were significantly underphosphorylated (two-sided p < .004) in tumors, whereas PKCs showed no differences from control samples.Second, although in control tissue there was a significant correlation between phosphorylation levels of Akt, MAPK, and PKC (all two-sided p < .05), many correlated activations were lost in tumors and even more in lymph node-positive tumors. Finally, p44 MAPK and Akt pThr308 were phosphorylated in a coordinated fashion only in lymph node-positive tumors (two-sided p < .01). CONCLUSIONS: This novel evidence documents important changes in the phosphorylation program during cancer progression of HNSCC.

Adult↗