Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer
British Journal of Cancer, 03/13/2014 Clinical Article
Malinowsky K, et al. – Patients with UICC/AJCC stage II colon cancer have a high 5–year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. The authors applied reverse–phase protein arrays (RPPA) for phosphatidylinositide–3–kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. This data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high–risk patients.
Full–length proteins were extracted from formalin–fixed, paraffin–embedded tissue samples of 118 patients who underwent curative resection.
RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide–3–kinase pathway.
Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel.
Expression of phospho–AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho–4E–BP1 (HR=4.12; P=0.011) were prognostic factors for disease–free survival.
None of the molecular genetic alterations were significantly associated with prognosis.
This company has it together. They have excellent people in charge, they have carefully constructed their plan and mission. The biomarker AKt1 may be the most important in all of CA and they are approaching it by using an ANS drug to go after it because the target is probably undruggable with small molecules, or even Mab's. Keep the faith, and have a three year time horizon and you will be richly rewarded. t
Archie, to flip it around the other way.....your presence here could be considered the kiss of death for this stock. Remember the last time, when your neighbor told you there was nothing wrong with LIPD and to buy more?? Uh-oh...t
Hey Archie, is that really you?? You still holding LIPD?? I wonder too Archie how many patients they have signed up? I also wonder what they paid to who for what. The CEO must be having fun. I can see him now, the secretary says "Mr. Beer, have Levi and Levi one line two. A few minutes later she says, "Mr. Beer, I'm sorry, you have Mr. Pomegratz on line three," a few minutes later it is "Mr. Beer, you have the Brazilian embassy on line one.". One product, one in the pipeline, one dead patient who only took on average 20mg per, the product is over twenty years old and the composite patent will only last another two years, a CEO that has potentially the DoJ after him, the Brazilian government after him, and about twelve law firms after him, that wants to do another survey to see really how many patients have HoF, who wants to do a survey to try and get poor kids on the med, who has really missed several earnings reports........whew what a company!! t
Now the Brazilan government is picking on poor AEGR, that after that darn old DoJ, and those twelve or more legal firms that are also going after them.....we need Mr. Beer to get those crocidolite tears like he used to get when talking about those poor people with HoF...before he started charging them 350K for a twenty year old drug.....darn jealous people. t
yep just buy the stock and it will be 65, then 180, then 1200, and then 6400 just like the big three have said all along......except they took most of their money out and then told everyone they were getting back in for the next leg(chicken leg) up. t
Halt_the-ranger it isn't inside info but will be common knowledge tomorrow. Maybe a fine, maybe a banning in Brazil, their second largest customer after the US, maybe a DoJ inquiry...another one?? t
No one has a totally safe drug, that includes Tylenol and aspirin. Ask people who took GSK's flu vaccine if vaccine's are totally risk free. t
Again you look out of touch. What rally are you talking about? And you double talk, you are down on me because I've said bad things about your stock....the truth, and yet you say that you and others have been out most of your stock before it went down and you are going to be piling back in again. So if you did sell you gave a no confidence vote to the company. Just like the architect. He said it was going to 1200 up to even 6400, but he had to sell for "other" reasons. Gee if I really thought a stock was going to 6400.....I'd find a way to wait. You find a way to be right by being off topic.....why don't you tell me about why your team didn't win the World Series, but that you picked the BS Red Sox all along. t
You don't know too much about lipids like I said. The big move up on Friday was the market not knowing too much about lipids either. The market thought that with the trouble that PCSK9 inhibitors may have in regards to more FDA hurdles to jump over that would give juxta an advantage. When in reality the two classes won't compete. For the most part PCSK9 inhibitors will do little to lower LDL in HoF patients as there are little or no LDLr receptors to shift upward, and juxta won't be used for HeF patients unless they do further studies which will take as long or longer than if PCSK9 inhibitors could be approved for HoF. So the big run up was a wall street mistake, not a tremendous approval for upcoming "profits" from the one drug wonder company that says it is in the business of treating orphan diseaseSSS. t
Keep talking, and keep on watching. Boy I wish you'd short the stock and bragg about it:))
You are so weird. My friends and I called it right and warned you about the fall before it came. You were wrong. Instead of at least listening to use you continued to be a big mouth and still not recognize the favor we did for you. You lied and tried to trick newbies in regards to your price targets of from 1200 to 6400. You were wrong in regards to Beer-gate. It will be bigger than you thought once we hear......even though you didn't want to admit, the company itself has with a recent news release to try and break the news more gently. You then try and play both sides against the middle stating that you and others....including halt-the-little-ranger left the stock to diversify and you didn't thus suffer the huge loss that you really did, but you are lying, or you lead other newbies to financial collapse with your 1200 to 6400 price target while you left like we advised you to. You are an amazing guy in your own mind. t
CGB activates ERK and AKT kinases in cancer cells via LHCGR-independent mechanism
Tumor Biology, 03/06/2014 Clinical Article
Glodek A, et al. – Expression of human chorionic gonadotropin free beta subunit (hCGβ) and its hyperglycosylated variant (hCGβ–H) is a phenomenon confirmed for tumors of different origin. Despite numerous studies, the mechanism of hCGβ action in cancer remains unknown especially that not all tumors secreting hCGβ express the receptor for human chorionic gonadotropin (LHCGR). The study also demonstrated that the presence of the receptor is a key factor influencing the magnitude of cells’ response.
Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer Full Text
BMC Cancer, 03/06/2014 Clinical Article
Agarwal E, et al. – Authors have reported that TGFβ/PKA/PP2A–mediated tumor suppressor signaling regulates Akt phosphorylation in association with the dissociation of survivin/XIAP complexes leading to inhibition of stress–dependent induction of cell survival. The identification of these 2 novel mechanisms leading to induction of cell death indicates MK–2206 might be a potential clinical candidate for therapeutic targeting of the subset of IGF1R–dependent cancers in CRC.
A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation Full Text
BMC Cancer, 03/07/2014 Clinical Article
Wiegand KC, et al. – The authors studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. Proteomic assessment of CCC and EC demonstrates remarkable differences in protein expression that are dependent on histotype, thereby further characterizing these cancers. AKT phosphorylation is associated with ARID1A/BAF250a deficient tumors, however in ovarian cancers the mechanism remains to be elucidated.
3-Bromopyruvate induces apoptosis in breast cancer cells by downregulating Mcl-1 through the PI3K/Akt signaling pathway
Anti-Cancer Drugs, 03/07/2014 Clinical Article
Liu Z, et al. – The hexokinase inhibitor 3–bromopyruvate (3–BrPA) can inhibit glycolysis in tumor cells to reduce ATP production, resulting in apoptosis. However, as 3–BrPA is an alkylating agent, its cytotoxic action may be induced by other molecular mechanisms. These findings indicate that 3–BrPA induces apoptosis in breast cancer cells by downregulating Mcl–1 through the phosphoinositide–3–kinase/Akt signaling pathway.
An important biomarker to maybe look out for and see if it is affected by Archexin is GOLF1:
renal cell carcinoma (RCC). These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.
Expression of GOLPH3 was examined in 43 fresh RCC tissues and paired adjacent normal renal tissues by real-time quantitative PCR and western blotting.
Immunohistochemistry for GOLPH3 was performed on additional 218 RCC tissues.
The clinical significance of GOLPH3 expression was analysed.
Downregulation of GOLPH3 was performed using small-interfering RNA (siRNA) in Caki-1 and 786-O cells with high abundance of GOLPH3, and the effects of GOLPH3 silencing on cell proliferation, migration, invasion in vitro, and tumour growth in vivo were evaluated.
Expression of GOLPH3 was upregulated in the majority of the RCC clinical tissue specimens at both mRNA and protein levels.
Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P