Random Records

Paper: Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer (doi:10.1073/pnas.0604206103) Abstract: Chromosomal instability (CIN+) 1. hallmark of most colon tumors 2. promote tumor progression by increasing rate of genetic aberration 3. occur from mitosis/spindle checkpoint defect Gap: Molecular mechanism is unk Rational: 1. colon cancer develop majorly from mutation of APC (Anaphase-promoting complex) 2. malfunction of APC causes wnt/b-catenin activation --> activate conductin/AXIN2 Research results: 1.wnt/catenin activation causes CIN via up-regulation of conductin 2.human colon cancer with CIN - found conductin higher 3.conductin is higher during the mitosis 4.conductin is localized with mitotic spindle of colon cancer cells 5.conductin binds polo-like kinase 1 6.when APC is forcibly downreglated by iRNA - conductin is ectopic upregulated lead to CIN in chromosomal stable colon cancer 7.higher expression of conductin di...

I really love this video, I have been interested in neuroplasticity for a while ago, I have been interested this term "neuroplasticity" while I was attending the SCPA501 course at the Department of Pathology. In the course, one of the group was assigned to present the Psychoneuroimmunology which is part of the immunological disorder. While I was searching for the Psychoneuroimmunology, neuroplasticity had come across. Dr. Lara Boyd from the University of British Columbia has given a wonderful TedTalk on the brain research. There are three key factors she mentioned in the talk that affect the neuroplasticity and of course the learning ability. 1. Chemical -- brain cells communicate each other by sending the signal to what we call as "neurotransmitter". It h appens very rapidly and it facilitates the short-term memory and motor skill (the ability to control the muscle). 2. Structural changes -- how brain cells rearrange as the network,  to support the communic...

Paper: Exome sequencing of liver fluke-associated cholangiocarcinoma (doi: 10.1038/ng.2273) Point out only the points that I have been interested. Whole exome sequencing: Expected result; -provide insight into mutational landscape contributing to OV-CCA -8 OV-related tumors and matched normal tissue *206 somatic mutations in 187 genes -validate bySangerr sequencing in another 46 cases (prevalent set) to detect recurrently mutated genes (15 genes) Known cancer-related genes: *TP53 -- 44.4% *KRAS -- 16.7% SMAD4 -- 16.7% Somatic mutation in newly identified genes; inactivation mutations *MLL3 -- 14.85% *ROBO2 -- 9.3% *RNF43 -- 9.3% *PEG3 -- 5.65% activating mutation GNAS -- 9.3% These group of gene mutations can be divided; 1. deactivation of histone modifiers 2. activation of G protein signaling 3. loss of genome stability Intro: CCA - *account for 10-25% of all primary liver cancers *western -- 1.5/100,000 in western countries (age-standardiz...

Paper: Reversing effect of ring finger protein 43 inhibition on malignant phenotypes of human hepatocellular carcinoma (doi: 10.1158/1535-7163.MCT-12-0672) Abstract: Gap- role of RNF43 in hepatocellular carcinoma is unk RNF43 is overexpressed in HCC and correlate *vascular invasion *poor tumor differentiation *advanced tumor stage Functional study (knock down): *induce apoptosis *inhibit proliferation *inhibit invasion *inhibit proliferation *inhibit colony formation *inhibit xerograft growth Microarray results: *229 genes different between KD and Vector *analysis of 229 genes involves many cellular process: -- cell proliferation -- cell adhesion -- cell motility -- cell death -- DNA repair -- etc. Suggested therapy: since RNF43 is related to tumorigenesis, it could be the drug target to treat HCC ---- Gap: there is the study of RNF43 on the colorectal cancer but not HCC ---- Finding: 1. RNF43 is highly expressed in the HCC and related to p...

Paper: Analysis of somatic microsatellite indels identifies driver events in human tumors (doi: 10.1038/nbt.3966) Again, I only note for the gene that I have been interested. Microsatellites; *variable-lengths repeats of short DNA motif (usually 1-6 repeat) *exhibit of high rate of mutation, esp, indel Gap: *the relationship of somatic MS indels to cancer is unk,  bc of the technical limitation What they do: Present two tools MSMUTect - accurate detection of somatic MS indels MSMutSig - identification of genes containing MS indels Apply the tool to whole-exome from -6747 human tumors; 20 tumors -identified new >1000 MS indels in cancer genes -be able to distinguish microsatellite -stable from microstellite instability -identified 7 MS indel hotspots: *ACVR2A, RNF43,JAK1,MSH3 (previously known cancer genes -- meaning support the tumor growth) *ESRP1,PRDM2 and DOCK3 --- MS; *repetitive short sequences (1-6 bp) *abundant in non-transcribed regio...

I have heard these two trails for the first time at JCMS2017 from Dr. Somponart (SISP). Besides, I have heard my colleague talked about her principal investigator want to examine whether cholangiocarcinoma has the mutations that are drugable to the current drug market, especially in Thailand, where not many choices of the affordable targeted therapy are available. I think it is quite useful, at least, for me to have a very short note on it. Article: Novel Precision Medicine Trial Designs Umbrellas and Baskets Ref: 10.1001/jamaoncol.2016.5299 Precision concept: Finding the specific mutations and get the precise drug to treat -- Before the precision medicine era: *one size fits all -- specific mutation driving cancer Trend is changing since new technology + minor population want to be completely free from cancer *initiate two new differential trail designs *Umbrella trial - focus on one type of cancers but different genetic mutations (based on its origina...

Paper: The cancer genome (doi: 10.1038/nature07943) Note only the part that I am interested. Step by step of changing in the genome: 1.Fertilized set considered as original 2.Somatic set 3.Germline set --- In somatic mutations for the cancer genome: 1.substitution in one base 2.insertion or deletion 3.rearrangement/broken and rejoining 4.copy number increase/decrease --- Exogenous gene causing cancer: Esp. from virus that integrates into the host genome -- *human papilloma virus (HPV) *Epstein Barr virus (EBV) *Hepatitis B virus (HBV) *human T lymphotropic virus 1 *human herpes virus 8 --- Structural genome: *epigenetic changes -- chromatin structure + gene expression *Epigenetic changes can be applied with Darwinian natural selection --- Mitochondria genome: circular 17 kb somatic mutations has been reported in many human cancers - exact roles are not clear Introduction of total genomic DNA from human cancers into phenotypically normal NIH3T3 cel...