ABSTRACT Salivary gland tumors are rare and most often benign. Malignant tumors consist mainly of... more ABSTRACT Salivary gland tumors are rare and most often benign. Malignant tumors consist mainly of carcinomas. The wide variety of subtypes of these rare tumors makes sometimes histological examination difficult. We present the main histological subtypes described by WHO, in order to better apprehend the management of these lesions.
Replication of the RNAs of influenza virus occurs in the nucleus of infected cells. The nucleopro... more Replication of the RNAs of influenza virus occurs in the nucleus of infected cells. The nucleoprotein (NP) has been shown to be important for the import of the viral RNA into the nucleus and has been proposed to contain at least three different nuclear localization signals (NLSs). Here, an import assay in digitonin-permeabilized cells was used to further define the contribution of these NLSs. Mutation of the unconventional NLS impaired the nuclear import of the NP. A peptide bearing the unconventional NLS could inhibit the nuclear import of the NP in this import assay and prevent the NP-karyopherin alpha interaction in a binding assay confirming the crucial role of this signal. Interestingly, a peptide containing the SV40 T antigen NLS was unable to inhibit the nuclear import of NP or the NP-karyopherin alpha interaction, suggesting that the NP and the SV40 T antigen do not share a common binding site on karyopherin alpha. We also investigated the question of which NLS(s) is/are nec...
Most RNA viruses that lack a DNA phase replicate in the cytoplasm. However, several negative-stra... more Most RNA viruses that lack a DNA phase replicate in the cytoplasm. However, several negative-stranded RNA viruses such as influenza, Thogoto, and Borna disease viruses replicate their RNAs in the nucleus, taking advantage of the host cell's nuclear machinery. A challenge faced by these viruses is the trafficking of viral components into and out of the nucleus through the nuclear membrane. The genomic RNAs of these viruses associate with proteins to form large complexes called viral ribonucleoproteins (vRNPs), which exceed the size limit for passive diffusion through the nuclear pore complex (NPC). To insure efficient transport across the nuclear membrane, these viruses use nuclear import and export signals exposed on the vRNPs. These signals recruit the cellular import and export complexes, which are responsible for the translocation of the vRNPs through the NPC. The ability to control the direction of vRNP trafficking throughout the viral life cycle is critical. Various mechani...
ABSTRACT AimsHuman equilibrative nucleoside transporter 1 (hENT1) level of expression in pancreat... more ABSTRACT AimsHuman equilibrative nucleoside transporter 1 (hENT1) level of expression in pancreatic ductal adenocarcinoma (PDAC) may predict survival in gemcitabine-treated patients after resection. These results have been obtained with a murine anti-hENT1 antibody (10D7G2), which is not commercially available. Another antibody, rabbit-derived (SP120), appears to have no predictive value in local, advanced or metastatic PDAC. This raises the question of the equivalence of the antibodies.Methods and resultsWe compared hENT1 expression with both antibodies in resected PAC.Results were correlated with overall survival (OS) following gemcitabine treatment. Two sets of patients (n=147 each) were stained with the SP120 antibody using different equipments, with an amplification technique for the set 2. The rate of “hENT1 high” cases was lower with the SP120 clone (set 1: 7 versus 48%, set 2: 11 versus 38%). With the amplification technique, the rate of “hENT1 high” cases was globally similar between both antibodies. However, the concordance between the antibodies was found in only 50% of cases. High hENT1 expression was predictive of OS only with 10D7G2 antibody (HR=0.49; 95% CI: 0.24-0.98; P=0.045).Conclusions The two antibodies are not equivalent. Further prospective studies seem warranted before using hENT1 testing in daily practice in PDAC.This article is protected by copyright. All rights reserved.
GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in... more GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient ...
GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in... more GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.
ABSTRACT Salivary gland tumors are rare and most often benign. Malignant tumors consist mainly of... more ABSTRACT Salivary gland tumors are rare and most often benign. Malignant tumors consist mainly of carcinomas. The wide variety of subtypes of these rare tumors makes sometimes histological examination difficult. We present the main histological subtypes described by WHO, in order to better apprehend the management of these lesions.
Replication of the RNAs of influenza virus occurs in the nucleus of infected cells. The nucleopro... more Replication of the RNAs of influenza virus occurs in the nucleus of infected cells. The nucleoprotein (NP) has been shown to be important for the import of the viral RNA into the nucleus and has been proposed to contain at least three different nuclear localization signals (NLSs). Here, an import assay in digitonin-permeabilized cells was used to further define the contribution of these NLSs. Mutation of the unconventional NLS impaired the nuclear import of the NP. A peptide bearing the unconventional NLS could inhibit the nuclear import of the NP in this import assay and prevent the NP-karyopherin alpha interaction in a binding assay confirming the crucial role of this signal. Interestingly, a peptide containing the SV40 T antigen NLS was unable to inhibit the nuclear import of NP or the NP-karyopherin alpha interaction, suggesting that the NP and the SV40 T antigen do not share a common binding site on karyopherin alpha. We also investigated the question of which NLS(s) is/are nec...
Most RNA viruses that lack a DNA phase replicate in the cytoplasm. However, several negative-stra... more Most RNA viruses that lack a DNA phase replicate in the cytoplasm. However, several negative-stranded RNA viruses such as influenza, Thogoto, and Borna disease viruses replicate their RNAs in the nucleus, taking advantage of the host cell's nuclear machinery. A challenge faced by these viruses is the trafficking of viral components into and out of the nucleus through the nuclear membrane. The genomic RNAs of these viruses associate with proteins to form large complexes called viral ribonucleoproteins (vRNPs), which exceed the size limit for passive diffusion through the nuclear pore complex (NPC). To insure efficient transport across the nuclear membrane, these viruses use nuclear import and export signals exposed on the vRNPs. These signals recruit the cellular import and export complexes, which are responsible for the translocation of the vRNPs through the NPC. The ability to control the direction of vRNP trafficking throughout the viral life cycle is critical. Various mechani...
ABSTRACT AimsHuman equilibrative nucleoside transporter 1 (hENT1) level of expression in pancreat... more ABSTRACT AimsHuman equilibrative nucleoside transporter 1 (hENT1) level of expression in pancreatic ductal adenocarcinoma (PDAC) may predict survival in gemcitabine-treated patients after resection. These results have been obtained with a murine anti-hENT1 antibody (10D7G2), which is not commercially available. Another antibody, rabbit-derived (SP120), appears to have no predictive value in local, advanced or metastatic PDAC. This raises the question of the equivalence of the antibodies.Methods and resultsWe compared hENT1 expression with both antibodies in resected PAC.Results were correlated with overall survival (OS) following gemcitabine treatment. Two sets of patients (n=147 each) were stained with the SP120 antibody using different equipments, with an amplification technique for the set 2. The rate of “hENT1 high” cases was lower with the SP120 clone (set 1: 7 versus 48%, set 2: 11 versus 38%). With the amplification technique, the rate of “hENT1 high” cases was globally similar between both antibodies. However, the concordance between the antibodies was found in only 50% of cases. High hENT1 expression was predictive of OS only with 10D7G2 antibody (HR=0.49; 95% CI: 0.24-0.98; P=0.045).Conclusions The two antibodies are not equivalent. Further prospective studies seem warranted before using hENT1 testing in daily practice in PDAC.This article is protected by copyright. All rights reserved.
GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in... more GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient ...
GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in... more GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.
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