Acral Metastasis in a Patient with Ampullary Carcinoma

Although Skin Metastasis From A Malignant Tumor Of An Internal Organ Usually Occurs At An Advanced Disease Stage, There Has Been No Prior Report Of A Cutaneous Acral Metastasis From Ampullary Carcinoma To Date. We Report A 71-year Old Male Patient With Cutaneous Metastasis From An Ampullary Adenocarcinoma. The Patient Had A History Of Pylorus Preserving Pancreaticoduodenectomy For Carcinoma Of The Ampulla Of Vater Two Years Prior To Presentation. Physical Examination Revealed Ill-defined, Painful And Hard Erythematous Nodules At The Left Thumb And Distal Phalanx Of The Right Middle Finger. The Computed Tomography Scan Showed Low Density Masses In The Retroperitoneum; The Histological Examination Of A Nodule From The Right Middle Finger Showed A Metastatic Adenocarcinoma. This Case Illustrates That Cutaneous Metastasis From Ampullary Carcinoma Has A Poor Prognosis

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection

TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy

Recent studies have suggested that activation of the EGFR pathway leads to malignant transformation only if the p53 protein is inactivated. Therefore, we evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT) sensitivity in combination with KRAS mutations that have been associated with cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64 metastatic colorectal cancer patients treated with cetuximab-based CT and correlated to clinical response using the Fisher's exact test. Times to progression (TTPs) according to gene status were calculated using the Kaplan–Meier method and compared with log-rank test. TP53 mutations were found in 41 patients and were significantly associated with controlled disease (CD), as defined as complete response, partial response or stable disease (P=0.037) and higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007). This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT

Expression and biophysical characterization of the human T1R1 taste receptor subunit

Expression and biophysical characterization of the human T1R1 taste receptor subunit. 21. Congress of the european chemoreception research organisation (ECRO

An efficient Escherichia coli expression system for the production of a functional N-terminal domain of the T1R3 taste receptor.

http://www.landesbioscience.com/International audienceSweet taste is mediated by a dimeric receptor composed of two distinct subunits, T1R2 and T1R3, whereas the T1R1/T1R3 receptor is involved in umami taste perception. The T1R1, T1R2, and T1R3 subunits are members of the small family of class C G protein-coupled receptors (GPCRs). The members of this family are characterized by a large N-terminal domain (NTD), which is structurally similar to bacterial periplasmic-binding proteins and contains the primary ligand-binding site. In a recent study, we described a strategy to produce a functional dimeric human T1R3-NTD. Although the protein was expressed as inclusion bodies (IBs) using the Escherichia coli system, the conditions for the refolding of functional hT1R3-NTD were determined using a fractional factorial screen coupled to a binding assay. Here, we report that this refolding strategy can be used to produce T1R1- and T1R2-NTDs in large quantities. We also discuss that our findings could be more generally applicable to other class C GPCR-NTDs, including the γ-aminobutyric acid type B receptor (GABABR), the extracellular calcium-sensing receptor (CaSR) and the large family of pheromone (V2R) orphan receptors

Recombinant expression, in vitro refolding, and biophysical characterization of the N-terminal domain of T1R3 taste receptor

Facteur d'impact (5 ans) : 1,617Notoriété à 2 ans : Acceptable (biochem.res.methods)The sweet taste receptor is a heterodimeric receptor composed of the T1R2 and T1R3 subunits, while T1R1 and T1R3 assemble to form the umami taste receptor. T1R receptors belong to the family of class C G-protein coupled receptors (GPCRs). In addition to a transmembrane heptahelical domain, class C GPCRs have a large extracellular N-terminal domain (NTD), which is the primary ligand-binding site. The T1R2 and T1R1 subunits have been shown to be responsible for ligand binding, via their NTDs. However, little is known about the contribution of T1R3-NTD to receptor functions. To enable biophysical characterization, we overexpressed the human NTD of T1R3 (hT1R3-NTD) using Escherichia coli in the form of inclusion bodies. Using a fractional factorial screen coupled to a functional assay, conditions were determined for the refolding of hT1R3-NTD. Far-UV circular dichroism spectroscopic studies revealed that hT1R3-NTD was well refolded. Using size-exclusion chromatography, we found that the refolded protein behaves as a dimer. Ligand binding quantified by tryptophan fluorescence quenching and microcalorimetry showed that hT1R3-NTD is functional and capable of binding sucralose with an affinity in the millimolar range. This study also provides a strategy to produce functional hT1R3-NTD by heterologous expression in E. coli; this is a prerequisite for structural determination and functional analysis of ligand-binding regions of other class C GPCRs

Expression of functional N-terminal domain of human T1R2 taste receptor

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Characterization of ligands for human T1R3 taste receptor

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À propos de 2 cas de glandes sébacées ectopiques œsophagiennes : corrélations endoscopiques, et anatomopathologiques sur biopsies et pièces opératoires

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