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Sono stati studiati il seno frontale e il seno mascellare nella loro evoluzione in rapporto alla neuropsicomorfologia

Si propone un innovativometodo di studio e di decifrazione del volto It is proposed an innovative approach to study and decode the face

We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit1 overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoter in vivo, and that these proteins positively regulate Pit1 promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and ?T3, that Pit1 overexpression increases pituitary cell proliferation. Finally, the expression analysis of HMGA1, HMGA2 and PIT1 in human pituitary adenomas of different histological types revealed a direct correlation between PIT1 and HMGA expression levels. Taken together, our data indicate a role of Pit1 upregulation by HMGA proteins in pituitary tumours.

The Authors have described a clinical case involving a patient with a classical TMJ syndrome and a full range of typical symptoms, both dental and non-dental. The patient underwent a set of EMG tests before his occlusal plane was restored using a special material, immediately following reconstruction and, lastly, three months following the application of a prosthesis. The findings of these EMG tests have shown that the complex symptoms reported by the patient could be traced back to his occlusal plane. Once it was reconstructed, all the typical dental and non-dental symptoms of TMJ disorders subsided.

span style="font-size: 12px; line-height: 14px" class="Apple-style-span"The Authors carried out an experimental study on a homogeneous group of young people to provide evidence of functional correlation among masticatory muscles and, indirectly, between changes to the interdental occlusal plane and modifications of the plantar arches due to talipes valgus and flat foot. In the two analysed conditions, the masticatory muscles undergo different functional alterations. This is due to the fact that the mechanoreceptors in the tendons of the muscles governing the plantar arch configuration are stimulated in different ways during the activation of long osteoarthromuscular chains. Dental specialists will have to take these correlation into account when diagnosing TMJ disorders./span

Background: The aim of the study was to evaluate the indications and surgical techniques for the treatment of gastroesophageal reflux disease. Methods: From 1998 through 2000, we performed gastroesophageal reflux surgery on 12 patients. Preoperative studies revealed third-degree esophagitis in most patients with no functional alterations of the esophagus itself. The patients underwent a laparoscopic Nissen-Rossetti fundoplication. No conversions to open laparotomy were necessary. The mean operative time was 180 minutes. Results: No intraoperative or immediate postoperative complications occurred. The mean postoperative stay was 6.2 days. Transitory postoperative dysphagia was noted in 8 patients. In 5 patients, it was mild and regressed after 2 weeks; in 3 cases, it was severe and regressed over 2 months. Conclusion: A laparoscopic surgical approach is a satisfactory method for correcting gastroesophageal reflux disease. The efficacy of medical therapy has been well established. However, in the young person who may be required to take medication for many years or in those persons who are intolerant of standard medical therapy for gastroesophageal reflux disease, a surgical intervention is a satisfactory option. The success of medical therapy can be used as a predictive criterion of the success of laparoscopic Nissen-Rosetti fundoplication when normal motility of the esophageal corpus is present.

Background: Peripancreatic fluid collection suggests the anatomical-clinical scenario of necrotizing acute pancreatitis. However, intrahepatic fluid collection is a rare occurrence with fewer than 30 cases being reported in the medical literature. We describe 2 cases of intrahepatic fluid collection in 2 patients with acute biliary pancreatitis and discuss the therapeutic possibilities. Case Reports: The first case report is that of a 68-year-old female with a diagnosis of acute biliary pancreatitis with several necrotizing fluid collections and a large infected intrahepatic collection in the left lobe. The patient was successfully treated by percutaneous US/CT guided drainage. The second case report is that of a 72-year-old female with a diagnosis of acute biliary pancreatitis with several peripancreatic fluid collections and a voluminous intrahepatic fluid collection in the left lobe that caused epigastric pain. This patient was also successfully treated with percutaneous US/CT guided drainage. Conclusion: Intrahepatic fluid collection in the course of acute biliary pancreatitis is a rare occurrence. The therapeutic approach is the same as that for pancreatic and peripancreatic fluid collections. In case of infection, the patient undergoes percutaneous US/CT guided drainage. This therapeutic procedure can be added to the therapeutic program for necrotizing acute biliary pancreatitis together with ERCP/ES and videolaparocholecystectomy (VLC).

Laaroscopic assisted right colectomy for carcinoma is a procedure with demonstrated feasibility. We want to evaluate the advantages.In the period 1999/2002 we have executed 7 laparoscopic right colectomy for carcinoma. We have compared the results with one group of 10 patients traditionally operated in the period 1998/2002. In both groups the oncologic staging was almost the same.Immediate results: operative time was 240' for laparoscopy vs. 150' for open operation; no anastomotic dehiscence for laparoscopy vs. 1/10 for open; no bronchopulmonary-thrombotic complications for laparoscopy vs. 2/10 for open, but there was 1/7 wound infection for laparoscopy vs. 1/10 for open; the return to the mobilization and normal diet was 3 days for laparoscopy vs. 7 days for open; the postoperative stay was 7 days for laparoscopy vs. 12 days for open.The two procedures did not condition differences neither in the extension of the resection and of the lymphectomy nor a different incidence of the anastomosis dehiscences. Differences were noted, in the operative time, in a more precocious mobilization with a minor use of analgesics, in a more rapid renewal of peristalsis and of feeding with a lower postoperative stay. These advantages are remarkable in our study, by reducing the postoperative morbidity. The very brief follow-up of almost 6 months, did not show a relapse of the disease in patients of both series.In our experience, laparoscopic-assisted right colectomy confirmed evident advantages in the immediate postoperative period for the treatment of the colonic cancer.

PATZ1 is an emerging cancer-related gene coding for a POZ/AT-hook/kruppel Zinc finger transcription factor, which is lost or misexpressed in human neoplasias. Here, we investigated its role in development exploring wild-type and Patz1-knockout mice during embryogenesis. We report that the Patz1 gene is ubiquitously expressed at early stages of development and becomes more restricted at later stages, with high levels of expression in actively proliferating neuroblasts belonging to the ventricular zones of the central nervous system (CNS). The analysis of embryos in which Patz1 was disrupted revealed the presence of severe defects in the CNS and in the cardiac outflow tract, which eventually lead to a pre-mature in utero death during late gestation or soon after birth. Moreover, the Patz1-null mice showed a general growth retardation, which was consistent with the slower growth rate and the increased susceptibility to senescence of Patz1(-/-) mouse embryonic fibroblasts (MEFs) compared to wild-type controls. Therefore, these results indicate a critical role of PATZ1 in the control of cell growth and embryonic development.

We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression ofGh,Prl,GhrhrandPit1itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role ofPit1overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoterin vivo, and that these proteins positively regulatePit1promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, thatPit1overexpression increases pituitary cell proliferation. Finally, the expression analysis ofHMGA1,HMGA2andPIT1in human pituitary adenomas of different histological types revealed a direct correlation betweenPIT1and HMGA expression levels. Taken together, our data indicate a role ofPit1upregulation by HMGA proteins in pituitary tumours.

Previous studies have demonstrated that high mobility group A proteins have a critical role on the onset of human pituitary adenomas. Indeed, both high mobility group A (HMGA) genes are overexpressed in pituitary adenomas, and consistently transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop mixed growth hormone/prolactin (GH-PRL)-secreting pituitary adenomas. Trisomy of chromosome 12, where HMGA2 is located, and/or amplification of the HMGA2 gene locus account for the HMGA2 overexpression in most human prolactinomas. Conversely, HMGA1 overexpression is not associated to any rearrangement or amplification of the HMGA1 locus. We have first identified micro RNAs (miRNAs) able to target both HMGA1 and HMGA2 messenger RNAs. Then, all of these miRNAs have been found downregulated in pituitary adenomas of different histotypes, compared with normal pituitary. Interestingly, their downregulation was also observed in nonfunctioning pituitary adenomas where HMGA2 overexpression is not associated to any alteration of the HMGA2 locus. Functional studies show that all these HMGA-targeting miRNAs inhibit the proliferation of the rat pituitary adenoma cell line GH3. Therefore, these results indicate that the downregulation of the miRNAs able to target the HMGA genes could contribute to increase HMGA protein levels in human pituitary adenomas, and then to pituitary tumorigenesis.Oncogene advance online publication, 5 December 2011; doi:10.1038/onc.2011.557.

DNA-damaging therapies represent a keystone in cancer treatment. Unfortunately, many tumors often relapse because of a group of cancer cells, which are resistant to conventional therapies. High-mobility group A (HMGA) proteins has a key role in cell transformation, and their overexpression is a common feature of human malignant neoplasias, representing a poor prognostic index often correlated to anti-cancer drug resistance. Our previous results demonstrated that HMGA1 is a substrate of ataxia-telangiectasia mutated (ATM), the main cellular sensor of genotoxic stress. Here we also report thatHMGA2, the other member of the HMGA family, is a novel substrate of ATM. Interestingly, we found that HMGA proteins positively regulate ATM gene expression. Moreover, induction of ATM kinase activity by DNA-damaging agents enhances HMGA-dependent transcriptional activation of ATM promoter, suggesting that ATM expression is modulated by a DNA-damage- and HMGA-dependent positive feedback loop. Finally, inhibition of HMGA expression in mouse embryonic fibroblasts and in cancer cells strongly reduces ATM protein levels, impairing the cellular DNA-damage response and enhancing the sensitivity to DNA-damaging agents. These findings indicate this novel HMGA-ATM pathway as a new potential target to improve the effectiveness of conventional anti-neoplastic treatments on the genotoxic-drug resistant cancer cells.Oncogene advance online publication, 21 February 2011; doi:10.1038/onc.2011.21.

HMGA1 gene rearrangements have been frequently described in human lipomas. In vitro studies suggest that HMGA1 proteins have a negative role in the control of adipocyte cell growth, and that HMGA1 gene truncation acts in a dominant-negative fashion. Therefore, to define better the role of the HMGA1 alterations in the generation of human lipomas, we generated mice carrying an Hmga1b truncated (Hmga1b/T) gene. These mice develop a giant phenotype together with a drastic expansion of the retroperitoneal and subcutaneous white adipose tissue. We show that the activation of the E2F pathway likely accounts, at least in part, for this phenotype. Interestingly, the Hmga1b/T mice also develop B-cell lymphomas similar to that occurring in Hmga1-knockout mice, supporting a dominant-negative role of the Hmga1b/T mutant also in vivo.

Impairment of the p27kip1 function, caused by a drastic reduction of its expression or cytoplasmic mislocalization, has been frequently observed in thyroid carcinomas. To understand the role of p27kip1 impairment in thyroid carcinogenesis, we investigated the consequences of the loss of p27kip1 expression in the context of a mouse modeling of papillary thyroid cancer, expressing the TRK-T1 oncogene under the transcriptional control of thyroglobulin promoter. We found that double mutant mice homozygous for a p27kip1 null allele (TRK-T1/p27−/−) display a higher incidence of papillary thyroid carcinomas, with a shorter latency period and increased proliferation index, compared with p27kip1 wild-type compounds (TRK-T1/p27+/+). Consistently, double mutant mice heterozygous for a p27kip1 null allele (TRK-T1/p27+/−) show an incidence of thyroid carcinomas that is intermediate between TRK-T1/p27−/− and TRK-T1/p27+/+ mice. Therefore, our findings suggest a dose-dependent role of p27kip1 function in papillary thyroid cancer development.

PATZ1 is a transcriptional factor functioning either as an activator or a repressor of gene transcription depending upon the cellular context. It appears to have a dual oncogenic/anti-oncogenic activity. Indeed, it is overexpressed in colon carcinomas, and its silencing inhibits colon cancer cell proliferation or increases sensitivity to apoptotic stimuli of glioma cells, suggesting an oncogenic role. Conversely, the development of B-cell lymphomas, sarcomas, hepatocellular carcinomas and lung adenomas in Patz1-knockout (ko) mice supports its tumour suppressor function. PATZ1 role in mouse lymphomagenesis is mainly because of the involvement of PATZ1 in BCL6-negative autoregulation. However, this does not exclude that PATZ1 may be involved in tumorigenesis by other mechanisms. Here, we report that PATZ1 interacts with the tumour suppressor p53 and binds p53-dependent gene promoters, including those of BAX, CDKN1A and MDM2. Knockdown of PATZ1 in HEK293 cells reduces promoter activity of these genes and inhibits their expression, suggesting a role of PATZ in enhancing p53 transcriptional activity. Consistently, Patz1-ko mouse embryonic fibroblasts (MEFs) show decreased expression of Bax, Cdkn1a and Mdm2 compared with wild-type (wt) MEFs. Moreover, Patz1-ko MEFs show a decreased percentage of apoptotic cells, either spontaneous or induced by treatment with 5-fluorouracil (5FU), compared with wt controls, suggesting a pro-apoptotic role for PATZ1 in these cells. However, PATZ1 binds p53-target genes also independently from p53, exerting, in the absence of p53, an opposite function on their expression. Indeed, knockdown of PATZ1 in p53-null osteosarcoma cells upregulates BAX expression and decreases survival of 5FU-treated cells, then suggesting an anti-apoptotic role of PATZ1 in p53-null cancer cells. Therefore, these data support a PATZ1 tumour-suppressive function based on its ability to enhance p53-dependent transcription and apoptosis. Conversely, its opposite and anti-apoptotic role in p53-null cancer cells provides the perspective of PATZ1 silencing as a possible adjuvant in the treatment of p53-null cancer. © 2013 Macmillan Publishers Limited All rights reserved.

The PATZ1 gene encoding a POZ/AT-hook/Kruppel zinc finger (PATZ) transcription factor, is considered a cancer-related gene because of its loss or misexpression in human neoplasias. As for other POZ/domain and Kruppel zinc finger (POK) family members, the transcriptional activity of PATZ is due to the POZ-mediated oligomer formation, suggesting that it might be not a typical transactivator but an architectural transcription factor, thus functioning either as activator or as repressor depending on the presence of proteins able to interact with it. Therefore, to better elucidate PATZ function, we searched for its molecular partners. By yeast two-hybrid screenings, we found a specific interaction between PATZ and BCL6, a human oncogene that plays a key role in germinal center (GC) derived neoplasias. We demonstrate that PATZ and BCL6 interact in germinal center-derived B lymphoma cells, through the POZ domain of PATZ. Moreover, we show that PATZ is able to bind the BCL6 regulatory region, where BCL6 itself acts as a negative regulator, and to contribute to negatively modulate its activity. Consistently, disruption of one or both Patz1 alleles in mice causes focal expansion of thymus B cells, in which BCL6 is up-regulated. This phenotype was almost completely rescued by crossing Patz1(+/-) with Bcl6(+/-) mice, indicating a key role for Bcl6 expression in its development. Finally, a significant number of Patz1 knock-out mice (both heterozygous and homozygous) also develop BCL6-expressing lymphomas. Therefore, the disruption of one or both Patz1 alleles may favor lymphomagenesis by activating the BCL6 pathway.