RET Fusion mutation drugs – lung cancer

Activated RET and ROS: two new driver mutations in lung adenocarcinoma

http://tlcr.amegroups.com/article/view/1031/1683

 

RET Inhibitors

Vandetanib

In April 2011 the FDA approved vandetanib, a RET, VEGF 2, VEGF 3 and EGF receptor tyrosine kinase inhibitor for the treatment of patients with metastatic MTC who were ineligible for surgery and had progressive or symptomatic disease. The approval followed the results from an open label single arm phase II study testing vandetanib in patients with hereditary MTC. This phase II study conducted by Wells et al.showed that 83% of the patients treated with vandetanib had a reduction in tumor size at their first assessment and 11 out of 30 patients responded with an initial decrease in tumor size ≥30% of which 6 (20%) had confirmed partial responses (PR) according to RECIST. Disease control rate at 24 weeks was 78% and the duration of response in patients with confirmed PR was durable with a median of 10.2 months (33). Following the phase II data a large phase III trial was initiated showing a significantly improved efficacy and prolongation of PFS for vandetanib compared to placebo in patients with sporadic and hereditary MTC with a hazard ratio of 0.46 (95% CI, 0.31-0.69; P<0.001) (34). Preclinical studies suggest that vandetanib has superior activity in MEN2B cell lines compared to cabozantinib (29). The predominant mutation in MEN2B is the activating M918T point mutation in the RET kinase domain, which is also the most frequent mutation in sporadic MTC (35). Vandetanib also showed activity against RET/PCT in vitro and in vivo (36).

Cabozantinib

Cabozantinib, a potent inhibitor of RET, VEGFR2 and MET tyrosine kinases, received FDA approval for its use in MTC in November 2012. Early signals of activity in MTC were seen in a phase I dose escalation trial, which led to the testing of cabozantinib in patients with MTC in an expansion cohort of the phase I study. Of the 35 patients with MTC and measurable disease included into the study 17 patients (49%) experienced a 30% or greater reduction in the sum of tumor diameters at first assessment. Disease control of at least 6 months was present in 68% of the patients (37). Following the positive data from the phase II study a large phase III study was started, which tests cabozantinibvs. placebo in patients with progressive, unresectable, locally advanced or metastatic MTC. First data were presented at ASCO 2012, which showed that the primary objective of significant PFS prolongation was met (HR 0.28 95% CI, 0.19-0.40; P<0.0001) (38).

In July 2012 a phase II study testing cabozantinib in KIF5B/RET positive NSCLC patients has been initiated at Memorial Sloan-Kettering Cancer Center (NCT01639508) and is thus to our knowledge the first study investigating a personalized treatment approach for this newly defined subgroup of NSCLC. Interestingly, in vitro studies showed a greater activity of cabozantinib compared to vandetanib in cell lines harboring the RET/PTC1 fusion gene, which also has been found in NSCLC (29).

Sorafenib

Sorafenib is a multi-tyrosine kinase inhibitor targeting VEGFR1, VEGFR2, KIT, RET, BRAF and CRAF (39). In vitro sorafenib was shown to inhibit RET in the low nanomolar range and exerted anti-tumor activity in RET-driven xenografts (40). Sorafenib has been tested in several phase II studies in patients with DTC, anaplastic thyroid carcinoma and MTC (4143). In an open-label phase II study of 41 patients with PTC, 6 patients (15%) showed a PR and 23 (56%) patients had a stable disease for longer than 6 months. The PRs seen in the patients were durable with a median duration of 7.5 months. The authors concluded that sorafenib is an active drug in metastatic PTC. Genetic testing was included into the trial and the great majority of PTCs harbored an activating BRAF mutation whereas none was positive for RET/PTC1 or RET/PTC3. These observations render translation into the RET driven NSCLC setting difficult (43). In another phase II study sorafenib was tested in locally advanced or metastatic MTC. Of 15 evaluable patients with sporadic MTC, one patient had a PR and more than 50% of the patients had SD ≥15 months. The majority of tumors in the tested population had activating mutations in the RET gene (42) The phase II study from Gupta-Abramson et al. demonstrated in 30 (27 out of 30 being DTC) patients with metastatic, iodine-refractory thyroid carcinoma a PR rate of 23% (7 patients). The median PFS was stated with 19.75 months. Data of specific genetic testing were not presented in this paper. Given the PR rate of 23% and the PFS of 19.25 months the sorafenib treatment may be considered superior to chemotherapy in these patients (41).

Sunitinib

Sunitinib is a multi-tyrosine kinase inhibitor targeting VEGFR, Flt-3, c-Kit and RET (40) and has proven to be a potent inhibitor of RET/PTC oncoproteins in vitro and in vivo (36). In a phase II study in iodine refractory DTC and MTC from 33 evaluable patients one patient showed a complete response (3%), ten patients had a PR (28%) and 16 patients demonstrated stable disease (46%). There was also a significant association seen between decreased 18FDG-PET uptake and RECIST response (44). Intermediate results of two studies testing sunitinib in patients with thyroid carcinoma were presented at ASCO 2008 (45,46). The study of Cohen et al. presented data of 31 evaluable patients with DTC treated for at least two cycles with sunitinib. Of these patients 13% showed a PR and 65% of patients a SD. In MTC there have been no PRs reported, but a SD rate of 85% (45) In a mixed patient cohort with MTC, DTC and anaplastic thyroid carcinoma Ravaud et al.demonstrated in 15 evaluable patients a PR rate of 7% (n=1) and a SD rate of 80% (n=12) (46). In addition two case reports have been published, one reporting a PR in a patient with MTC and one in a patient with PTC treated with sunitinib (47,48).

Motesanib

The multi-tyrosine kinase inhibitor motesanib inhibits VEGFR, PDGFR, Kit and RET and demonstrated activity in TT tumor cell xenografts expressing the RET C634W protein (49). But there have also been reports indicating the ineffectiveness of motesanib in inhibiting the C634W mutant form of RET and being only active in wild type RET (50). Motesanib was tested in two phase II studies involving patients with thyroid cancer. One study which included 93 patients with confirmed locally advanced metastatic DTC or MTC yielded a 14% PR rate and a 68% SD rate. However none of the patients genetically analyzed showed a RET mutation or RET rearrangement in their tumor (51). Another phase II trial studying motesanib in MTC included 91 patients. In this trial only 2% of the patients were reported to have achieved a PR and 81% of the patients had a SD. The objective response rate for RET-mutation negative (n=10) and for RET-mutation positive (n=28) was 10% and 0%, respectively (50).

Anti-aging combo on Amazon

Amazon links.

N (R) Niagen Nicotinamide Riboside

https://www.amazon.com/Niagen-Nicotinamide-Riboside-60-capsules/dp/B00L5Q951S/ref=sr_1_2_s_it?s=hpc&ie=UTF8&qid=1474577659&sr=1-2&keywords=niagen

Pterostilbene Longevity and Antioxidant Supplement

https://www.amazon.com/Pterostilbene-Resveratrol-Longevity-Antioxidant-Supplement/dp/B00JQS5T76/ref=sr_1_2_s_it?s=hpc&ie=UTF8&qid=1474577726&sr=1-2&keywords=Pterostilbene

Pterostilbene inhibits lung cancer through induction of apoptosis.

http://www.ncbi.nlm.nih.gov/pubmed/20031166

Cancer Notes

Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375728/

Inhibitors of RET, a tyrosine kinase receptor encoded by a gene that is frequently mutated in medullary thyroid cancer, have emerged as promising novel therapies for the disease. Rapalogs and other mammalian target of rapamycin (mTOR) inhibitors are effective agents in patients with gastroenteropancreatic neuroendocrine tumors, which share lineage properties with medullary thyroid carcinomas. The objective of this study was to investigate the contribution of mTOR activity to RET-induced signaling and cell growth and to establish whether growth suppression is enhanced by co-targeting RET and mTOR kinase activities.

The goals of this study were to determine whether oncogenic RETregulates mTOR activity in MTC and PTC cells and whether targeted inhibition of these two kinases shows cooperative effects on growth suppression. mTOR activity was exquisitely RET-dependent in all cell lines tested. Treatment of RET mutant thyroid cancer cell lines with the RET kinase inhibitor NVP-AST487 profoundly inhibited their growth. Similar effects were noted when these cells were treated with the mTOR kinase inhibitor INK128. However, their combination at high concentrations showed no additive effect, pointing to a possible common mechanism of action. Indeed, when combined at lower concentrations, the RET and mTOR kinase inhibitors showed strong cooperativity. These results indicate a critical role of mTOR signaling in RET-induced cell growth and provide strategies to maximize therapeutic effects when toxicity precludes using RET kinase inhibitors at their maximally effective dose.

Pterostilbene inhibits lung cancer through induction of apoptosis.

http://www.ncbi.nlm.nih.gov/pubmed/20031166

Lung cancer remains the leading cause of cancer mortality in the United States. Resveratrol is a potent antioxidant found in grapes that inhibits several types of cancer, including lung cancer. Herein, we investigated the effects of pterostilbene, an analog of resveratrol found in blueberries, on lung cancer, in vitro. We hypothesized that pterostilbene would inhibit lung cancer cell growth in vitro by a pro-apoptotic mechanism.

METHODS:

Two lung cancer cell lines (NCI-H460 and SK-MES-1) were cultured using standard techniques. Cells were treated with increasing doses of pterostilbene (10-100 microM). Cell viability was measured at 24, 48, and 72h using a MTT assay. Apo-ONE Caspase-3/7 assay was used to evaluate caspase activity. T-test and two-way ANOVA were used for statistical analysis.

RESULTS:

Pterostilbene significantly decreased cell viability in lung cancer cells in a concentration- and time-dependent manner (P<0.001). Concentrations greater than 20 microM of pterostilbene produced significant growth inhibition by 72h (P<0.001). Apoptosis and caspase-3/7 activity were significantly increased by pterostilbene treatment (P<0.05).

CONCLUSIONS:

Pterostilbene inhibits growth via apoptosis induction in vitro. Further in vitro mechanistic studies and in vivo experiments are warranted to determine the potential role for pterostilbene in lung cancer treatment or prevention.

 

Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276376/

A Combination of Pterostilbene With Autophagy Inhibitors Exerts Efficient Apoptotic Characteristics in Both Chemosensitive and Chemoresistant Lung Cancer Cells

http://toxsci.oxfordjournals.org/content/137/1/65.full

 

Geroncogenesis: Metabolic Changes during Aging as a Driver of Tumorigenesis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970212/

Sirtuins Are Central to Metabolic Reprogramming during Aging and Cancer

Table 1

Evidence for Sirtuins as Tumor Suppressors or Promoters

Another sirtuin implicated in tumorigenesis is SIRT6, a chromatin-associated enzyme with deacetylase and long-chain deacylase activities.Sirt6 deletion increases HIF-1α and c-Myc transcriptional activity, with a corresponding upregulation of glycolysis (Sebastián et al., 2012;Zhong et al., 2010). Remarkably, knockdown of Sirt6 in otherwise normal mouse embryonic fibroblasts (MEFs) transforms them, independently of activation of known oncogenes (Sebastián et al., 2012). Although SIRT6 is required for genomic stability (Mostoslavsky et al., 2006), re-introduction of Sirt6 into knockout MEF cells in which genomic instability might already have been expected to take place represses tumor formation, effectively ruling out mutations as a cause (Sebastián et al., 2012). These findings further underscore the idea that metabolic alterations are required, if not sufficient, to induce tumor growth.

SIRT1, a nuclear sirtuin, was the first family member shown to act as a tumor suppressor. Pharmacological activation or genetic overexpression of Sirt1 increases genomic stability in cells treated with DNA-damaging agents, delays lymphoma, and improves the survival of irradiated p53+/−mice (Oberdoerffer et al., 2008), while Sirt1 deletion has the opposite effect (Wang et al., 2008). By localizing to sites of DNA damage and facilitating the recruitment of DNA repair factors such as histone deacetylase 1, Rad51, and Nbs1, SIRT1 plays a key role in promoting genome stability, a function that declines with age (Dobbin et al., 2013;Oberdoerffer et al., 2008). One of the strongest effects of SIRT1 in vivo is its ability to protect mice in the heterogeneous diethylnitrosamine-induced model of hepatocellular carcinoma (Herranz et al., 2010), potentially by suppressing inflammatory responses in this organ. SIRT1 can also suppress tumorigenesis by negatively regulating oncogenic transcription factors, including β-catenin (Firestein et al., 2008) and c-Myc (Yuan et al., 2009), though opposing findings for Myc have been reported (Menssen et al., 2012).

Similar to SIRT3 and SIRT6, SIRT1 might influence tumorigenesis, not only through its ability to regulate genomic stability, but also by regulating cellular metabolism. SIRT1 regulates the transcriptional activity of HIF-1α (Lim et al., 2010), which is also an important regulator of the Warburg effect as well as angiogenesis and metastasis. SIRT1 also deacetylates and activates liver kinase B1 (LKB1; Lan et al., 2008), a known tumor suppressor that regulates mTOR and AMPK (Sedelnikova et al., 2004). Interestingly, the effects of SIRT1 on tumorigenesis are context dependent. For example, inhibition of SIRT1 improves the efficacy of a chemotherapeutic agent (Imatinib) against chronic myeloid leukemia (Li et al., 2012) and blocks the proliferation of hepatocellular carcinoma cell lines in vitro and in a xenograft model (Portmann et al., 2013). Conversely, Sirt1 overexpression can accelerate thyroid cancers in vivo (Herranz et al., 2013). These latter findings likely reflect the ability of SIRT1 to inhibit the tumor suppressor p53, which promotes survival under situations of cell stress (Luo et al., 2001).

There is evidence that SIRT2, the cytosolic sirtuin, is also a tumor suppressor. Deletion of Sirt2 results in spontaneous tumorigenesis in the liver and accelerates the 7,12-dimethyl-benz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate model of skin cancer (Narayan et al., 2012; Serrano et al., 2013). One mechanism is likely to be cell cycle control, as SIRT2 deacetylates and regulates CDH1 and CDC20, members of the anaphase-promoting complex (Narayan et al., 2012). Moreover, SIRT2 transiently migrates to the nucleus during mitosis (North and Verdin, 2007), where it modulates the activity of the methyltransferase PR-Set7, resulting in H4K20 methylation (Serrano et al., 2013), a chromatin mark involved in genomic stability (Oda et al., 2009). Although primarily studied in the context of its cytosolic regulation of cell cycle, one interesting possibility is that SIRT2 influences mitochondrial function and the Warburg effect by deacetylating CDH1, a protein that limits glycolysis and proliferation of cancer cell lines through ubiquitination and degradation of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase (Almeida et al., 2010). Again, the data are not clear cut; an in vitro study found that SIRT2 knockdown or small molecule inhibition reduced neuroblastoma cell growth through stabilization of Myc oncoproteins (Liu et al., 2013).

Recently, two other sirtuins, SIRT4 and SIRT7, have also been implicated in the regulation of tumorigenesis. The mitochondrial sirtuin SIRT4 promotes metabolic reprogramming by facilitating the cataplerotic diversion of carbons from the TCA cycle to aerobic glycolysis and lactate generation, forcing cancer cells to rely on glutamine for replenishment of the TCA cycle (Csibi et al., 2013; Jeong et al., 2013). Upon DNA damage, Sirt4 expression is upregulated, leading to a repression of glutamine metabolism through its inhibition of glutamate dehydrogenase, which converts glutamate into α-ketoglutarate (Csibi et al., 2013; Jeong et al., 2013). This shift prevents the cell from upregulating nonessential biosynthetic pathways and undergoing premature cellular division prior to genomic repair (Csibi et al., 2013;Jeong et al., 2013). The nucleolar sirtuin, SIRT7, may also regulate cellular metabolism by negatively regulating HIF-1α and HIF-2α (Hubbi et al., 2013), potentially underlying the Warburg effect. The role of SIRT7 in tumorigenesis, however, also seems context dependent: SIRT7 may help maintain a pro-oncogenic phenotype by interacting with the transcription factor ELK4 and deacetylating H3-K18, a modification that promotes tumor growth (Barber et al., 2012).

Beyond Resveratrol: The Anti-Aging NAD Fad

http://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/

NAD+ and SIRT1: Their Role In Chronic Health Issues

 

NAD+ and SIRT1: Their Role In Chronic Health Issues

 

Snowden should be pardoned

Letter to the Editor

Whistle blower Edward Snowden who revealed information about the illegal Bush/Obama NSA spying program is a national hero and should be pardoned. Yes – what he did was illegal. But if he didn’t act that too would have been illegal. The NSA had been lying to Congress about what it was doing and that it was illegally spying on every single person in America. We only know that because of Snowden.

Since Snowden’s revelation Congress changed several laws in order to help put a stop to the conduct that Snowden revealed. This to me indicates that Snowden did America a national service and that his actions to stop illegal government spying was justified. I therefore join in the call to pardon Edward Snowden.

Putin like Trump because he’s weak and stupid

Letter to the Editor

I find it somewhat amusing that presidential candidate Donald Trump thinks that Russian president Putin likes him is a good thing. Putin is a power hungry dictator who wants to restore the former Soviet Union to power, and the best think that could happen for Putin is to have an incompetent American president that is weak and stupid. Do we really want to elect a president that is endorsed by America’s adversaries? I don’t think so!

I have bad news. I have stage 4 lung cancer

I have some very bad news.

For the last 25 years I have been one of the nations most prolific letter to the editor writers. Unfortunately that might come to and end soon as I have been diagnosed stage 4 lung cancer. As someone who understand probabilities far too well I understand this is a fatal diagnosis and it’s just a matter of when. My life is now a casino and it’s mostly all about luck at this point.

Since 1991 I have written some 2500 letters to the editor, all 100% original, and I have mass distributed them to about 2000 newspapers each time. Back in the early days it was by fax. If you remember the old Sprint “Free Fridays” where long distance was free on Friday, I would write a letter every Thursday and queue it up. At the stroke of midnight 3 fax servers would come on line and fax 2000 papers and often every member of Congress weekly. In the late 1990s I switched to email.

I am usually well published because I understand that short is better, talking about current events, and laying out my points as clearly as possible and a flair for humor. This allowed my original opinions, right or wrong, to reach untold millions of people over the years. And I want to express gratitude to all of you who have published my work over the last 1/4 century.

It’s actually rather ironic that I of all people should be dying of lung cancer as someone who is a lifelong anti-smoking activist. I feel the cancer gods owe me a favor.

I suppose I’m now the new Christopher Hitchens – the dying Atheist. But I’m really not the same. Where Atheism is ultimately about nothing, Realism is about everything. And for the past 18 years I’ve been developing my Church of Reality and leave behind a reality based philosophy of life that is based on science. Trying to get it so logically tight that when computers become smarter than humans and have an existential crisis wondering “What is the meaning of artificial life?”, that I have an answer that it can reason is valid.

In that context I face my “final adventure” with the comfort of knowing that I have lived an extraordinary life and that I have accomplished more that most people do in 100 lifetimes. I have always looked at life as a story. Your story is everything you do from birth to death, and then your story is how you affected the world. Leonard Nimoy is gone, but Spock is still with us. At an early age I chose to “own my story” as I call it in my religion, to “live the life worth living”.

No one has a perfect life and as I look back there’s lots of things I could have done better. But surprisingly I feel that I have lived a life well lived and that is very comforting to me right now. And because of that I have a huge number of friends who care a lot about me, so much so that is is very humbling. And I’m dealing with making a lot of people very sad right now and that’s difficult to do. I’m not used to being on the receiving end of generosity. Even a little guilty that I might not have been as generous with them as they are with me.

For someone with a death sentence I’m doing OK so far. I have a paid for home in California, and still make a good income from home doing my little tech empire, web hosting and spam filtering. I’m not feeling any symptoms yet so if not for the diagnosis I would not know I was sick. So I’m writing this early in the process while I’m still in an inspirational state of mind. A very close friend of mine who is a hospice nurse, told me that people die the way they lived. So I’m hoping that’s true. (Although I’m probably going to be cranky and difficult as I get sick.)

I’m not afraid to be dead. I’m more afraid of the process of getting there. I had thought there was a chance that with new technology that I might be young enough to cheat death. That with the genetic work being done by Dr. David Sinclair and the advancements in computers that I when I die I would be “uploaded to the cloud where I would live forever.” (What does that remind you of?) But, if humanity stay on the right path, I might be the last generation to die. But seems I’m going to miss out on that one.

I however have a larger view of existence. We live in a universe where stars evolve into astronomers, and since we are all created by the universe what we do is what part of the universe is doing. We are the physical mechanism where self awareness and contemplation lives. “I think therefore I am.” However some 3.5 billion years ago something in the bottom of the ocean started dividing and formed life and we are all that organism still dividing and evolving. And although we are all individuals, in a greater sense we are all a single biological organism as well. But views are true, the only different is perspective and scale.

Much of what we know we know collectively. We are tightly integrated into a society more closely integrated than a hive of bees. The very words we use to think our own thoughts with are words invented by other people. And humanity explores the universe collectively. But since we are the universe, when we look back through the Hubble Telescope, the universe is looking at baby pictures of itself. As Carl Sagan says, we are the mechanism through which the universe contemplates it’s own existence.

Although I feel the impending loss of my own existence, in the greater sense I am more like a single cell in a greater organism who is created, lives for a time, and passes on. And although my story will end, my story will become part of the story of humanity, which is part of the story of life, and part of the story of the universe. And because of technology much more of who I am will survive as I upload what’s left of me to my digital afterlife. My hardware will return to dust, but some of my software will live on. And I’m hoping that I will achieve a meaningful level of immortality in that the values and wisdom I leave behind represent the essence of who I am (was) as a person. And that part is the part that has real value.

Still, this is all very difficult, I’m still have some denial of what’s happening to me. And I’m hoping that I die well. And the process of disassembling my personal existence is scary. Although what I write sounds very brave to read, there is a lot of fear inspiring it.

And although it sounds like I’m giving up, I am going to put up a fight. I’m going to MD Anderson which is the best cancer hospital in the nation. My life is a casino right now, but they are the casino with the best odds. If I get 2 years that would be a win. But I understand the probability spectrum way too well to not plan for a fatal outcome. I suppose I need to get around to writing a will.

I can ramble on forever, and forever isn’t as long as it used to be.

Feel free to distribute this or to publish this as well if you want to. I also do great interviews. Might be useful to other people facing their own mortality.

Marc Perkel

Insurance Companies Aetna and Humana should not be allowed to merge

Letter to the Editor

In a move to intimidate the Justice Department insurance giant Aetna threatened to pull out of Obamacare if government regulators interfered with its merger with Humana. The health insurance merger should not be allowed to continue.

The reason that the government regulates the super corporation is to prevent one company from having so much leverage that they can bully America into doing what they want. Aetna, in making this threat is displaying the very behavior that the monopoly laws are designed to prevent. If Aetna is threatening America now, how much more will they threaten America when they merge and become even bigger?

As someone who has lung cancer I want to make sure that the insurance companies are not in a position to take my money for years and then throw me out on the street without care to increase their corporate profits. I think there was a missed opportunity in 2010 to eliminate the insurance companies altogether and pass single payer health care and eliminate these parasites from American society. But if the Justice Department can’t stand up to bullies when they are smaller, how are they going to stand up to them when they get bigger? We are already paying the price of letting the banks grow to “too big to fail”. Why would we let the insurance industry do the same thing?

John McCain does not deserve reelection

Letter to the Editor

Senator John McCain, a former prisoner of war in Vietnam, has endorsed Donald Trump in spite of the fact that Trump has advocated the use of torture on prisoners. Trump has also disparaged prisoners of war like McCain calling him and all POWs losers because they were captured. And Trump jokes about soldiers who get Purple Hearts and families who lost sons in battle.

I’m beginning to wonder about McCain’s POW story because what kind of person allows Trump to say those things and still endorse him. McCain in his endorsement of Trump throws himself and every other soldier who has sacrificed under the bus. It as if McCain no longer remembers the years he spent in captivity. And if McCain has forgotten he loyalties as a soldier I think it’s time we forget about McCain. Perhaps Trump is right about McCain being a loser.

Wow! Do I ever miss Bill Clinton

Letter to the Editor

After seeing Bill Clinton speak tonight I no longer care if Hillary is lying about whatever. I want Bill Clinton back in the White House!

I was expecting Trump to grow up

Letter to the Editor

I watched Trump’s acceptance speech at the convention and his behavior since and he’s is acting like a brat. I’m talking about this ongoing feud between Trump and Cruz. In the primary it was amusing. It was refreshing to get some unfiltered opinions, no matter how weird they may be.

But the primary is over and now it’s time to pivot to the issue of “What are you going to be like as a president?” issue. So I was expecting Mr. Trump to be inspirational and adult, and I’m not seeing that. Trump is focused on this personal grudge match to get even with Ted Cruz. This is what ill behaved children do. Does it really matter if “Ted Cruz’s father hung with Lee Harvey Oswald” after the primary is over?

Donald – you won. You beat Cruz. Declare victory and move on. I have to ask the question, “Are you going to at least grow up and act like an adult?” It’s time for Trump to start acting like a president. Donald, show me your presidential side.

Clinton picks Big Bank Advocate for VP

Letter to the Editor

It is very unfortunate that Hillary Clinton picked a VP running mate who is advocating for the deregulation of banks just 8 years after deregulation caused a economic collapse and added some 10 trillion dollars to the national debt. While the big banks got bailed out, the American people got royally screwed. Tim Kaine is the exact opposite of consumer advocate Elisabeth Warren.

Trump’s accusation that Clinton is just a puppet of Wall Street appears to be true. In 2008 big banks crashed the economy and they got away with it because of Obama’s “too rich to jail” policy where none of the bankers who ripped America off were punished.. I had thought Hillary was the lesser of two evils. Now I don’t know who is worse. All I know for sure is that the next president is going to be really really bad.

Republicans have already lost the Presidential Election

Letter to the Editor

The Republican Party is slowly grasping the reality that they have already lost the presidential election. I’m not saying that Trump isn’t going to win. I’m saying that Trump is not, never was, and never will be a Republican. The Republican voters chose a non-Republican over 16 other Republicans. And I think the Republican Party deserves it.

The Republican Party have been in a downward spiral for decades. It had degraded to where candidates were just puppets of special interests and crazy billionaires. This time Republican chose to go with the crazy billionaire instead of the puppet and I can’t say I blame them. In fact, as someone who votes Democrat as the lesser of 2 evils I find myself just a little be envious. And isn’t that just more than a little bit sad,

Why can’t Americans see the last 28 pages?

Letter to the Editor

After America was attacked on 9/11 there was an investigation and a report was issued. However the last 28 pages of the 9/11 report remain secret, classified by the Bush administration. Apparently the 28 pages are not something that Saudi Arabia wants released and they have threatened to sell off some 750 billion in American assets if the information is revealed. The information is thought to indicate involvement of the Saudi Royal Family in the 9/11 attack.

Now the Obama administration and the Republican leaders have caved into Saudi demands and Obama has threatened to veto legislation that would make the 28 pages public. So after America is attacked American’s are denied the right to know who did it because of Wall Street, Big Oil, and the Saudi Royal Family come before the interests of the American People. It would appear that we are not a nation of the People, by the People, and for the People. America is owned by the Arab oil cartels, and isn’t that more than just a little bit sad.

Are we really having a primary election?

Letter to the Editor

I used to think America was a Democracy where the People elected the politicians and our votes counted. But that doesn’t seem to be the case in this year’s election. This year the Democrats and Republicans have rigged their primaries. And that’s neither Democratic, nor the American Way.

In a Democracy the person with the most votes wins the election. On the Republican side that person, at this point is Donald Trump. Personally I despise Trump but if he wins he wins. But what I’m hearing is that party insiders want to give the election, not to Trump, not even to Cruz, but to some unknown person that the party insiders will choose themselves. Maybe someone who hasn’t even run or has already dropped out of the race.

On the Democrat side you have a race in Wyoming where Bernie Sanders slaughters Hillary Clinton by 56 to 44. You would think that Bernie would get more delegates than Hillary, but you would be wrong. When Bernie wins he doesn’t win. Both get half. why is that? Because the Democrat Party rigged the election in favor of Hillary and made the super delegates vote last year before the primary season began. Super delegates politicians electing politicians usurping the vote of the People.

These parties make up the rules and the rules are that the vote of the People doesn’t matter. They are merely giving us the illusion of voting when the elections are rigged from the start. And I’m refusing to participate in a general election that is rigged against Sander and Trump. The people are rising up. We’re mad as hell and we’re not going to take it anymore. We have had enough of presidents like Bush and Obama and we are telling the party insiders we want someone else. And we are not going to stand by and allow our elections in America to be conducted by the same rules used by the Communists and third world dictatorships.

Denying Supreme Court Numinee a Hearing

Letter to the Editor

There is a Constitutional question I’ve been wondering about. The President shall have the power to justices of the Supreme Court “by and with the Advice and Consent of the Senate”. But what happens if the Senate refuses to participate in the process as they are doing now with Judge Garland.

If the Senate refuses to advise and consent (as opposed to denying consent) could that be construed as a waiver of their rights and the nomination is not blocked? The question is if they have an affirmative duty to confirm rather than a right to deny. Is “not voting” mean a required “yes” is denied, or and optional “no” is not asserted? I think the phrase “by and with the Advice and Consent of the Senate” mean that the Senate can participate and can block a nominee by voting to deny. But I also think that when the Senate says that they are refusing to advise and consent then they are waiving their option to participate, So when the Senate says they refuse to vote, as they have said, then the nominee becomes the next justice.

I think someone should look into this.

I’m tired of Billionaires controlling the election

Letter to the Editor

America has had terrible presidents for the last 16 years. First we had Bush who crashed the economy and got us into wars in the middle east. Then we had Obama who passed out trillions of dollars to the super rich and let the bankers get away with it. No bankers were prosecuted because Obama decided they were “too rich to jail”.

Now we have candidates on both sides that are either billionaires or the puppets of billionaires. Donald Trump wants to sell of 16 trillion in America’s assets, our assets, to pay the same super rich people who we bailed out in 2009. There is just one candidate who is standing up to the oligarchy that now controls American politics, and that one candidate is Bernie Sanders. That’s why I’m supporting Bernie. If he doesn’t win then Democracy itself might die out.

Trump being honest about Abortion

Letter to the Editor

People on the left and right are criticizing Trump for saying the if you make abortion illegal that women who get abortions would go to jail. After all, that is what the word illegal means. When people oppose abortion they don’t think things through. That’s why we need to keep abortion legal so that we can choose to have children when we want to, not when the government throws women in jail for not having babies.

Violence at Trump Rallies is Trumps Fault

Letter to the Editor

Donald Trump started this and what happened Friday in Chicago was Donald Trump’s fault. Trump started it by encourage violence at his political rallies. Trump said about a protester “I’d like to punch him in the face, I’ll tell you that,” and offered to pay the legal expenses of those who commit violent acts against those who don’t agree with him. He also reminisced about the “good old days” when protesters were taken out on stretchers.

This is America and when you are a political candidate who threatens violence against protesters you get violence. Trump might be able to intimidate his fellow Republican candidates but if he thinks that the electorate is going to allow him to incite a riot then Americans are going to stop him. I’m surprise that Trump wasn’t arrested for the things he’s said because it’s illegal for him to get up in front of an audience and tell the crowd to go beat people up. So as far as I’m concerned if Trump doesn’t do a total reversal on his violent rhetoric then I support what the good people of Chicago did to shut him down.

Money does Influence Politics

Letter to the Editor

Like Secretary Clinton, President Obama took Wall Street money and look at what happened. None of the bankers who ripped us all off went to jail. In the 1980s President Reagan sent 700 bankers to jail. So I have to agree with Senator Sanders that money corrupts. Under Sanders there will be no “too rich to jail”.

I have to agree with Sanders about wanting to hear the $200,000 speech Clinton made to Wall Street. I feel like the super rich really ripped off everyone and got away with it and I would like to know what she is saying to them behind closed doors. I can’t vote for someone who tells me one thing but secretly is selling us out in the back room. If she has nothing to hide then why is she hiding it from us?

Hillary’s Email Problem

Letter to the Editor

A lot of people are arguing about Hillary Clinton’s email problem. Is it a big deal or is it a big deal over nothing? But I think people are missing the real point here. The government goes to a lot of trouble to make sure that the Secretary of State has a secure email system so that when the Secretary of State gets email about things like helping Egypt overthrow their president, support for Syrian rebels, or when we are going in to kill bin Laden, that no one else gets to intercept these communications.

The bottom line is that if Hillary had just followed the rules and used the State Department email system like she was supposed to we wouldn’t be having this discussion. Hillary chose to ignore the rules and have someone on her campaign staff set up an email server at her home instead. When you’re the Secretary of State you just can’t be that sloppy with national security. Quite frankly, I’m somewhat amazed that the Obama Administration let her get away with that.

Difference between Clinton and Sanders is …

Letter to the Editor

I think there’s really one defining difference between Hillary Clinton and Bernie Sanders in this presidential race. Bernie’s message is “Yes we Can” and Hillary’s message is “No we Can’t” on issues like single payer heath care and free college tuition. It reminds me of the 2012 election when Bill Clinton won against poppy Bush who didn’t have “The Vision Thing”. I can’t get behind someone who starts out believing that progress isn’t possible. I supported Hillary in 2008 and my favorite president ever is Bill Clinton, but this year I’m feeling the Bern.

Does Obama want Trump to be the Republican Candidate?

Letter to the Editor

President Obama did a press conference today where he said, “I continue to believe Mr. Trump will not be president”. I believe he’s sincere about that but it makes me wonder if Obama realizes that he has effectively endorsed Trump for Republican nominee. If you’re Republican and you don’t know who to vote for – then the easy choice is to vote for the guy who Obama doesn’t want you to vote for. So – either Obama wants Trump to be the nominee or Obama didn’t think things through very well. Either way – it’s disturbing.

Republicans challenge the President of Scalia

Letter to the Editor

Now that there is an opening on the Supreme Court the Republicans are saying that they will refuse to process and appointments that President Obama will make. That they will refuse to allow Obama to make the choice even though he is still president. It makes me wonder if they would take that same stance if it were the last year of a Republican presidency. The Republicans are challenging the authority of the presidency because they think Obama is weak. It will be interesting to see if President Obama will have the guts to stand up and do what the President is supposed to do.

People are tired of Republicans and Democrats

Letter to the Editor

Donald Trump and Bernie Sanders have something in common. Donald Trump isn’t a real Republican and Bernie Sanders isn’t a real Democrat, and that’s why I think they are so popular right now. People are tired of Republicans and Democrats. First we had 8 years of Bush who collapsed the economy. Then we had 7 years of Obama who taught us that Hope and Change is really Nope and Same. Americans on the Left and on the Right have had it with them and now we want someone else. We’re mad as Hell and we’re not going to take it anymore.

In the case of Trump, the other Republican candidates are just puppets of their crazy billionaire sponsors. Trump is his own crazy billionaire. He’s no one’s puppet. Bernie Sanders has a long history of saying what he means and meaning what he say. Some people may not like his positions but everyone knows where he stands. I have always been a big fan of Bill Clinton but Hillary is no Bill Clinton. She’ll say anything to get elected.

With Sanders and Trump drawing crowds of 10s of thousands America is telling the parties that the insanity has to end. So let’s have a contest between people who aren’t just more of the same kind of political hacks we are tired of.

Clinton Email Very Disturbing

Letter to the Editor

People are wondering if Hillary Clinton’s email scandal is something to worry about and the short answer is – yes it is. She was the Secretary of State and in that role she had access to top secret information that only the top people in government knew. For example – when we are moving in to kill Osama bin Laden Hillary is pictured in the room with Obama watching it all unfold. She was involved with Iran nuclear weapons talks,  the wars in Syria, Egypt, Libya, and Tunisia. When you are dealing with these kinds of important issues, you don’t do that on a home server that is filtered through a commercial spam filtering service.

I’m somewhat amazed that the Obama administration and the State Department let her get away with it. They all had to have known because her email address wasn’t @state.gov, it was @clintonemail.com, So the other people in the Obama administration knew what she was doing and just let her do it. As an email professional myself I sit here with my mouth open in utter amazement as to why they let her get away with that. Her email setup was less secure than if she had used her personal Yahoo account.

SpaceX makes history!

Letter to the Editor

I want to congratulate Elon Musk and SpaceX for making history today by landing the first stage of a rocket back on Earth (in one piece this time) after deploying a payload into space. This is an historic event because the cost of getting stuff into space just got at least 3 times cheaper.

In a world where news is dominated by ISIS, mass shootings, and Donald Trump it’s time the smart people get the spotlight and we have good news to report. This event is another milestone representing the progress of humanity on a road that will eventually lead to the human colonization of the planet Mars. All of humanity rejoices tonight at this great accomplishment. Thank you Elon and the team at SpaceX.

Ben Carson not a threat to “progressive secular movement”

Letter to the Editor

Ben Carson says that the reason that people are looking into his past is that he’s a threat to the “progressive secular movement”. I think he’s more of a threat to religion than he is to us heathen atheists. Religious people are supposed to be inspired by God to tell the truth and as someone who claims to be a religious person Ben Carson’s behavior represents what he really believes. So if he’s lying and trying to blame non-believers then he’s really no threat to us. Carson is a threat to religious people.

When someone cloaks himself in the Word of God and uses that to lie, then what that says is that he really doesn’t believe in God. Ben Carson is an atheist just like us. I think if someone is going to lie they should take personal responsibility for their actions and not try to hide behind Jesus and point fingers at non-believers for his personal sins. If I were a Christian Carson would be an embarrassment.

I have no idea who Ben Carson really is, but he’s doing a really bad job of pretending he’s something that he’s not. Trump might be a lunatic, but he’s genuine.

Candidates should be asked about NSA Spying

Letter to the Editor

Whether you are a tree hugging liberal or from the Ku Klux Klan conservative one thing we all have in common is that we don’t like the government spying on us. Now we are in the debate season to determine who is going to be president and those who question the candidates are not asking the tough questions. Where do they stand on NSA spying? Where do they stand on Edward Snowden? Those are the questions I want to see asked in the debates.

Jailing Clerk over Gay Marriage is right thing to do

Letter to the Editor

I think the jailing of Kim Davis, the Kentucky Clerk who refused to issue marriage licenses to same sex couples was the right thing for the judge to do. Like many older Americans I think gay marriage is “a little weird”. But this is America where people have the freedom to be a little weird. That’s what living in a free country is all about.

Likewise as a Christian Kim Davis talks to invisible people, which is also “a little weird”. But if a gay clerk refused to issue her a marriage license because she was strange – well – that would be wrong. Just like Seventh Day Adventists who don’t take jobs where they are required to work on Saturday, if Kim Davis can’t do what she is required to do because of her religion, she should get a job that is compatible with her beliefs

Pope moves in right direction on Abortion

Letter to the Editor

I find myself again praising Pope Francis, His latest change on abortion is a step in the right direction. As a non-catholic I didn’t know abortion was an unforgivable sin and that it was just upgraded to forgivable.

I personally don’t think abortion is a sin at all. In fact – there are already too many people on the planet and people shouldn’t have one till they they are ready to do it right. Global warming is really caused by too many people and when you have a finite sized planet and a growing population you have a disaster waiting to happen.

So – thumbs up to the Pope for moving in the right direction.