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Note: p38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells (doi: 10.3892/ijo.2018.4353) Cowanin is pure cmp. from Garcinia cowa (Chamuay); Crude extract from tree; 1. antitimor activity 2. inflmmation induction 3. antibacterial activity 4. anti-inflammatory activity 5. antimalarial activity Purpose of this study, 1. effects of cowanin on apoptosis induction 2. effect on apoptosis-related protein kinase 3.mitogen-activated protein kinase Target cell line -- LoVo human colorectal cancer cell line Assay test; 1. MTT assay (viability assay) 2. Nuclear morphological change by Hoe staining 3. Mitochondrial membrane potential by JC-1 staining Cowanin inhibits cell proliferation and induced cell dead via apoptosis pw. Cowanin induce all apoptotic related molecules through MAPK and Akt signaling pw. Therefore, the author suggested that cowanin might be a good candidate to treat colorectal cancer. T...

Note: LIG4 mediates Wnt signaling-induced radioresistance (doi: 10.1038/ncomms10994) This work is very nice piece and easy to follow step by step to test their hypothesis. Focus tumor: CRC Cell line used (endogenous environment): SW620 HCT116 HT15 COLO205 HCC2998 KM12 Cellular event marker: g-H2Ax --> DNA double-strand break Reporter for wnt-acivity: 7TGP Reporter for functional stem cell (using the genetic engineered approach): telomerase reverse transcriptase ( TERT ) --> expressed only in self-renewing cells Inhibitor: iCRT14 -- break the interaction between b-catenin-TCF--> no transcription occur (less LIG4) SCR7 -- break the interaction between LIG4-DNA-->no DNA repair by LIG4 b-catenin targeted genes (transcript product): CD44 CD133 Axin2 Wnt is related to radioresistant but the underly mechanism is unk --> therefore, this study want to investigate. How it links to DNA repair? --> Wnt regulates the stemness and thi...

Paper: RNF43 is frequently mutated in colorectal and endometrial cancers (doi: 10.1038/ng.3127) Before that there were the studies showed that RNF43 was the oncogene in colorectal cancer which meant that cancer cell overexpress this gene in order to keep the cancerous characteristic. Ten years later, this study showed that RNF43 was the tumor suppressor gene in MSI-colorectal cancer. The new discovery relies on the new technology as well as the way to categorize the cancer subtype, at the very beginning it depended on the cellular histology under the microscope, and lately, it has been shifted to the molecular level which can inform more detail on the pathogenesis, disease progression and the treatment outcomes. Note on this paper; colorectal cancer and endometrial cancer -- Wnt-dependent tumor type; MSI-common 1. whole exome sequencing of colorectal cancer (FFPE; 185 samples) 2. found out large number of RNF43 non-silent mutations; 18.9% of case 3. found fram...

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: Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas (doi: 10.1038/sj.onc.1205518) Abstract: Most colon cancer develop from: -adenoma (benign tumor of epithelial tissue with glandular origin) to carcinoma Gap: unk molecular mechanisms of this transition Aim: -analyzing gene-expression profiles of 20 colorectal tumors using microarray 23,040 genes panel *9 adenomas (pre-malignant) *11 differentiated adenocarcinomas (malignant) Result: -identified 51 upregulate vs normal colonic epithelium -identified 376 downregulate vs normal colonic epithelium -identified 50 different between adenomas vs carcinomas ---- Intro: -Mention about the advance stage of colorectal cancer which therapeutic is not effective -Seek for early stage detection of colorectal cancer or pre-malignant lesion - block before further advance development Results: 1. 771 genes passed the determined criteria 2...

Paper: A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer (doi:10.3892/ijo.25.5.1343) Abstract: 1. Analyze expression profiles of 20 colorectal tumors by microarray - found genes upregulate in CRC - but look more detail on RNF43 2. northern blot reveals - undetectable in normal tissue - low expression in fetal kidney and lung 3. growth promoting effect in - COS7 - NIH3T3 4. RNAi - limit the growth of colon cancer 5. Secretory protein and have the autocrine effect - can be used as novel diagnostic marker for CRC CRC occurs from genetic alterations: Tumor suppressor/Onco - APC, p53, beta-catenin and K-ras Epigenetic affect - methylation, loss of imprinting, other unk Gap for CRC: 1.Advance stage of CRC results in high mortality 2. Development of sensitivity and specific diagnostic biomarkers to detect early stage, developing more  effective and less harmful therapeutic drugs (to be able to design this kind of thing - re...