Malignant melanoma of the gastrointestinal tract: symptoms, diagnosis, and current treatment options.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments

Role of S100 Proteins in Colorectal Carcinogenesis

The family of S100 proteins represents 25 relatively small (9–13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κβ signaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy

Age, puberty and attractiveness judgments in adolescents

Previous work has suggested that judgments of the attractiveness of some facial and vocal features change during adolescence. Here, over 70 Czech adolescents aged 12–14 made forced-choice attractivenessjudgments on adolescent faces manipulated in symmetry, averageness and femininity, and on adolescent opposite-sex voices manipulated in fundamental frequency (perceived as pitch), and completed questionnaires on pubertal development. Consistent with typical adult judgments, adolescents selected the symmetric, average and feminine male and female faces as more attractive significantly more often than the asymmetric, non-average and masculine faces respectively. Moreover, preferences for symmetric faces were positively associated with adolescents’ age and stage of pubertal development. Unexpectedly, voice pitch did not significantly influence adolescents’ attractivenessjudgments. Collectively, these findings present new evidence using refined methodology that adolescent development is related to variation in attractivenessjudgments

Distinguishing between Incomplete Lineage Sorting and Genomic Introgressions : Complete Fixation of Allospecific Mitochondrial DNA in a Sexually Reproducing Fish (Cobitis; Teleostei), despite Clonal Reproduction of Hybrids

Peer reviewe

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care

Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance of promoter 1B in normal colorectal mucosa (from controls), expression levels of specific transcripts from each of the promoters, 1A and 1B, were examined, and the expression from 1B was significantly higher compared with 1A. Significant amounts of transcripts generated from promoter 1B were also determined in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from mutation carriers in Family 1 for second hits in the entire gene without any findings, however, loss of the residual expression of the deleterious allele was observed. Three major conclusions of significant importance in relation to the function of APC can be drawn from this study; (i) germline inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require homozygous inactivation of APC allowing for alternative genetic models as basis for adenoma formation

Mise en récit et théâtralisation dans le jeu en psychothérapie d'enfants : de l'archaïque au symbolique

« Il était une fois... Cette thèse aborde le lien entre l'expression théâtrale et son utilisation clinique dans la psychothérapie d'enfants. Partant du questionnement sur les origines du théâtre et de la thérapie dans l'histoire de l'humanité, donc du substrat « archaïque » de l'homme et de sa relation à l'art scénique, la première partie développe une réflexion autour des rituels, du chamanisme et de la notion du soin. Purement théorique, elle soulève cependant la question de l'identité de l'Homme dans les sociétés postmodernes et traite de la thématique du développement psychique de l'enfant au sein de notre société occidentale ainsi que des souffrances qui en amènent certains vers les consultations psychologiques La partie principale s'articule autour de six histoires cliniques d'enfants suivis en psychothérapie expressive, récits dans lesquels la médiation théâtrale et corporelle devient 1 outil central du soin. En se développant sur la base d'une mise en narration des histoires imaginaires des enfants qui reflètent leurs angoisses archaïques, 1 univers thérapeutique prend alors la forme d'une scène psychique ouvrant a la symbolisation à travers le jeu théâtral. Parallèlement à la description de ce dispositif, une élaboration est menée autour des échanges transférentiels et con re transferentiels ainsi que sur la position du thérapeute - son rôle de « médium malleable » - dans la relation à l'Autre qui se tisse dans un « ici et maintenant » de la rencontre psychotherapeutic. Grâce à cet univers ludique s'enracinant dans son vécu psycho-fantasmatique, l'enfant devient l'acteur agissant de sa propre transfonnation : une évolution du monstre archaïque en sa créature symbolique. -- « Once upon a time... » This thesis treats the link between theatrical expression and its clinical use in children s psychotherapy. Originating from interrogations on the origins of theatre and therapy in the history of mankind, therefore the « archaic » substratum of Man and his relation to the theatre. The first part develops a reflection around rituals shamanism and the notion of care. In a purely theoretical way, it brings up the ques ions of Man's identity in post-modern societies and deals with the psychic development of children in western society and the pains that lead some to seek for psychological consultations. The main part hinges on six clinical stories of children in expressive psychotherapy, m which theatrical and coiporal mediation become the main tool within he treatment. By putting into narration, the children's imaginary stories that reflect their archaic anxiety, therapy takes in the shape of a psychic scene, which opens to symbolization through acting. At the same time, an elaboration is lead on transferential and counter-transferential exchanges as on the therapists position - his role as « malleable medium » - his interactions with others as a «here and now » in the psychotherapeutic encounter. Thanks to this playful universe, which emerges from his psycho-fantasy past, the child becomes the willing actor of his own transformation: the evolution of the archaic monster into its symbolical creature