NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

Doc logic,

He likes to debate with individuals that he considers his equals; individuals who don't mess up in their explanation of the science; individuals that get him to get to think through what he might be missing. I don't think he considers me one of them. I'm surprised that's not apparent. :)

He honestly does take a 360 degree view. Of that I'm certain. But the pick choice needs to be his. If it's not he'll only scratch the surface. He really looks for holes in his own theories and enjoys debating. But obviously prefers to feel challenged when he does so. He truly likes to vett both side. In this case, I honestly think that UCLA writing through him off and he won't let it go until someone like AVII comes along and shows where he's wrong. Flip could do it too, but he often doesn't have the tolerance or patience, and then the debate becomes personal.

Pyrr does have a nice side. He really wants the best for me. He treats me with tough gloves and wants me to learn scientific and regulatory things. I highly respect his opinions, I just don't always agree with them. He pretends he's fine with it when I and others disagree with his thought. He feels his knowledge, reasoning, resolves is sound and well argued. But, I don't think he ever fine when he feels disrespected. His temper flares up in the way he spars sometimes. I hit a nerve when I told him that Woodford had seen the patents. He didn't like that. At all.

He equates my investment success to luck. And he thinks it will run out. He disregards my intuition; and my intelligence, at times. He gets annoyed with me when I'm impressed by small arm data. He thinks I'm wrong all the time. He doesn't have the same respect for my research or opinions, as I do for his, but he does like me as a person. So, no I disagree, he doesn't see that I won this debate or any other. He stopped looking, listening and caring. But I said it nonetheless.

I'm glad though that this board sees that I did prove they use the right methods. Me being right doesn't mean they will be successful. However, it does mean that they at least are testing the science's potential accurately. I hope he eventually covers his short before it hurts him. Maybe one day he will see that "hard work beats talent when talent doesn't work that hard." I don't have a big ego, regardless of what some here think. Him included. I have no problem admitting when I'm wrong or when I go too fast. Here I haven't. And here I am not. I work hard at investing. I do my research. I right about this, and Hypericin too. I hope you don't mind, but here's a little something from his freeze thaw document, the chart within and related documents proves it. He still won't agree on either.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862689/pdf/onci-2-e26260.pdf

Autophagy-dependent suppression of cancer immunogenicity and effector mechanisms of innate and adaptive immunity

Figure 1. Autophagy induced in the course of hypericin-based photodynamic therapy dampens the immunogenicity of cell death and hence inhibits the elicitation of anticancer immune responses. (A) Photo-oxidative endoplasmic reticulum (phox-ER) stress induced by hypericin-based photodynamic therapy (Hyp-PDT) stimulates the efficient pre-apoptotic trafficking of damage-associated molecular patterns (DAMPs) including calreticulin (CRT) and ATP toward the extracellular environment. Hyp-PDT-induced ICD potently induces the phenotypic maturation of dendritic cells (DCs) as well as their functional activation, characterized by the production of immunostimulatory cytokines such as interleukin (IL)-6 and IL-1ß in absence of immunosuppressive IL-10. In turn, activated and mature DCs induce potent cellular immune responses featuring the proliferative expansion of CD4+ and CD8+ T lymphocytes that secrete interferon ? (IFN?) production. (B) Hyp-PDT-stress induced autophagy dampens ER stress, the accumulation of oxidized proteins and the exposure of CRT on the cell surface (but not ATP secretion), hence inhibiting the maturation of DCs as well as their ability to secrete IL-6 and to sustain the proliferation of (IFN?-producing) CD4+/CD8+ T lymphocytes. (C) Baseline levels of autophagy in untreated/healthy cancer cells also suppress CRT exposure, IL-6 production by DCs and the proliferation of CD4+ and CD8+ T lymphocytes.


ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death

Abstract
Calreticulin surface exposure (ecto-CALR), ATP secretion, maturation of dendritic cells (DCs) and stimulation of T cells are prerequisites for anticancer therapy-induced immunogenic cell death (ICD). Recent evidence suggests that chemotherapy-induced autophagy may positively regulate ICD by favoring ATP secretion. We have recently shown that reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress triggered by hypericin-mediated photodynamic therapy (Hyp-PDT) induces bona fide ICD. However, whether Hyp-PDT-induced autophagy regulates ICD was not explored. Here we showed that, in contrast to expectations, reducing autophagy (by ATG5 knockdown) in cancer cells did not alter ATP secretion after Hyp-PDT. Autophagy-attenuated cancer cells displayed enhanced ecto-CALR induction following Hyp-PDT, which strongly correlated with their inability to clear oxidatively damaged proteins. Furthermore, autophagy-attenuation in Hyp-PDT-treated cancer cells increased their ability to induce DC maturation, IL6 production and proliferation of CD4(+) or CD8(+) T cells, which was accompanied by IFNG production. Thus, our study unravels a role for ROS-induced autophagy in weakening functional interaction between dying cancer cells and the immune system thereby helping in evasion from ICD prerequisites or determinants.