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PTM for Histone; 1. acetylation (Lys) 2. ubiquitination (Lys) 3. phosphorylation (Ser) H2Ax when phosphorylate --> gammaH2Ax! nucleosome = histone (H2A,H2B,H3,H4) + 147 bp DNA wrapping around 8 octa-histone and being locked with H1 (shown in my drawing) For H2A subdivided to 3; H2A1-H2A2 (balance from the other two) H2Ax (2-25%) H2Az (10%) Ref; DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 ( J Biol Chem.  1998 Mar 6;273(10):5858-68.)

Paper: RSPO3 antagonism inhibits growth and tumorigenicity in colorectal tumors harboring common Wnt pathway mutations doi: 10.1038/s41598-017-15704-y I would like to start with my rough drawing since it can help me recognize by heart now. The concept of this paper relies on Wnt signaling that contributes to the growth of colorectal tumors. Mutation of genes in Wnt pathway that related to CRC is beta-catenin, APC and RNF43 and these type of mutations are found 90% of CRC. My understanding, this paper points out the microenvironment supporting the tumor growth. Not only Wnt ligand but also R-spondin is the ligand that can activate the Wnt signaling pathway. Wnt binds to the Fz directly whereas R-spondin (RSPO) quantitatively control RNF43. RSPO binds to RNF43 which leads to proteasomal degradation, therefore, controlling the availability of Fz on the membrane. It was shown that RSPO3 antagonism worked effectively with RSPO gene fusion type (RSPO-PTPRK) in CRC...

Paper: Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma doi: 10.1073/pnas.1307218110. Epub 2013 Jul 11 I like the picture that the team showed the cytotoxicity assay toward PDAC cell lines by using Wnt secretion inhibitor; LGK974. LGK974 inhibits the wnt-secretion by inhibiting the enzyme called "porcupine" which add the palmitoleic acid to the wnt as an indispensable signal for its secretion. What I have learned in this publication is molecular subtyping is a very important procedure for the cancer treatment since each molecular subtype will differently response to the treatment. The main idea for this paper is that; 1. PDAC cell lines have a different molecular genotypic signature. 2. There is more than 1 factor that supporting the growth of PDAC cell lines. 3. The growth of RNF43 malfunctioned PDAC cell lines relies on the Wnt pathway (by understanding this characteristic, we can apply the wnt inhibitor to this patient...

Paper: Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents doi: 10.1016/j.bbamcr.2014.01.005. Epub 2014 Jan 10 It is a little bit complicated to imagine how RecQL5 repairs the damage from interstrand crosslink (ICL) agent, like in this case cisplatin and mitomycin C. RecQ-family; DNA helicase (denature DNA duplex) - maintenance genome stability Focus on RecQL5 - RecQL5 - tumor suppressor - interact with Rad51- displace Rad51-ssDNA Gap; Precise role of RecQL5 is elusive. Results; 1.RecQL5 is involved in DNA interstrand crosslink (cisplatin, mitomycin C) repair. 2.Phenotype of RecQL5 KO resembled to FA gene KO cells 3.RecQL5 is involved in FANCD1 (BRCA2)-dependent ICL repair 4. Disappear of Rad51-foci delayed in REQL5KO cells after MMC treatment 5. Rad54 delayed Rad51-ssDNA in HR, compare to RecQL5 6.RecQL5 sensitivity to CDDP, and delayed Rad51-ssDNA detachment. 7.RecQL5 and Rad54 have a different effect on Rad51-ssDNA det...

I have read the news and view in the nature which summarizes two articles demonstrating the tumor cells, esp. lung adenocarcinomas (advanced and aggressive stage) divided and gave rise to two cell populations. ( doi :10.1038/nature22494) 1. tumour cells - actively dividing cells 2. supporting cell or so called "niche cell" - which provide the microenvironment to support the growth of the tumour cells Picture indicates the tumour cell divides and gives rise to two subpopulations (a). Within the tumour tissue, there are two cell subpopulations, one support the growth of tumour by which it secretes the growth factor that can stimulate the tumour cell growth (b). Question remains; supporting cell can secrete and promote the cancer growth in the other cancer type besides the its own neighbouring cells

Paper: Targeting DNA Repair in Cancer: Beyond PARP Inhibitors (doi: 10.1158/2159-8290.CD-16-0860) There are two main concepts for the DNA repair targeting, as far as I have observed; 1. if using as the monotherapy, then we have to understand the genotype of tumor cells; which mutation signature that causes tumor cells remain "the particular DNA repair mechanism". 2. if using as adjuvant therapy, it means administrated as the combination with the current cytotoxic drugs, and observe the genotype of cancer cells --> which DNA repair pathway predominantly used by the tumor cells and target that. Genetic signature of cancer cells is very important to use a tool to predict the therapeutic treatment choice. --- Here comes to what I want to make a note from this paper. DNA damage response; 1. how cell sense the damage 2. how cell sense the signal 3. how cell activate the cell cycle checkpoint 4. how cell trigger apoptosis 5. how cell orchestrates to initiate DNA ...

My friend has just sent me this paper and I have just finished skim through it. This is the note for myself on paper (it is quite fun to read and get the ideas both from the paper and from my friend); Paper -- Improved prediction of PARP inhibitor response and identification of synergizing agents through use of a novel gene expression signature generation algorithm (doi:  10.1038/s41540-017-0011-6). The team used two different databases to generate the algorithm ( iterative resampling analysis to predict sensitivity -- IRAPS) 1. Cancer cell line encyclopedia (focus on solid tumor cell line) --> contains the genotypic as well as gene expression profile of each cancer cell line 2. Genomics of drug sensitivity --> shows the relationship between the mutational status of cancer cells that are sensitive to particular drugs After generating the algorithm, they used theirs to test with the available cohort, in this case, cisplatin treatment which lacks a good responsive ma...