http://www.umassmed.edu/globalassets/immunology-and-microbiology/documents/papers-for-bbs821-2015/nov-24-reviewfor-general-info.pdf

Role of the Microbiota in Immunity and Inflammation

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.

/pdf/fast-tree-computing-large-minimum-evolution-trees-with-4grq0gwfpy.pdf

Fast Tree: Computing Large Minimum-Evolution Trees with Profiles instead of a Distance Matrix

The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1600266

The Human Intestinal Microbiome in Health and Disease

Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(07)70410-2.pdf

Gastroenteropancreatic neuroendocrine tumours.

3520Background: Curative surgery is the best therapy of CRC and recurrences. We assessed whether adding semi-annual PET-CT to the usual surveillance would be cost-effective in high risk recurrent C...

Colorectal cancer (CRC) patients surveyed by 18FDGPET-CT (PET-CT): An open-label multicenter randomized trial (NCT 00624260).

Conjugal severe acute colitis

There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.

Gastrin processing in primary culture of gastrinoma cells.

Plusieurs genes impliques dans la regulation de l'appetit et du metabolisme energetique ont ete clones a partir de modeles animaux d'obesite genetique. Les produits de secretion correspondants ont ete identifies et les recepteurs relayant leurs actions biologiques, caracterises. Ces produits ont pour chef de file la leptine, un maillon essentiel du systeme complexe de regulation de la prise alimentaire. Les mecanismes impliques dans l'action « anti-obesite » de la leptine sont complexes car la leptine, par l'intermediaire de son recepteur hypothalamique, interagit avec de nombreux neuropeptides dans le systeme nerveux central, pour controler le bilan energetique. Outre le tissu adipeux, d'autres organes dont l'estomac produisent la leptine. La leptine gastrique qui est synthetisee par les cellules principales secretant egalement le pepsinogene agirait par voie endoluminale pour controler les fonctions du tractus gastro-intestinal.

Iradj Sobhani

Papers

Colorectal cancer (CRC) patients surveyed by 18FDGPET-CT (PET-CT): An open-label multicenter randomized trial (NCT 00624260).

Conjugal severe acute colitis

Gastrin processing in primary culture of gastrinoma cells.

Leptine, obésité et tractus gastro-intestinal

Anomalies de prolifération des cellules argyrophiles fundiques (enterochromaffin-like) dans le syndrome de Zollinger-Ellison