Thursday, March 26, 2015

Interlude

We are back
after Robotic surgery
and 12 days of Intubation
which has left us deconditioned
Physical therapy is working with us
now I can write again
but my signature is still hard
already the literature has piled up
science continue to progress

Friday, February 6, 2015

Articles review

*Daratumumab added action to Revlimid and Decadron in Myeloma we are told!
*New important pathway :  The PLK1 disturbing spindle cell assemby...
*Blinatumomab, beneficial in refractory B cell precursor ALL....
*Potentiation of T cell  tumor recognition (of neoplastic transformation)
by  1.   Anti-CTLA4-----Ipilimumab
      2.   Anti-PD1----PEMBRO
      3.   CAR-T cell therapy
*Volarsetib in AML for older patient (research)
*Adding Everolimus to Taxol-Herceptin failed to increase disease free survival.   But it did in Her-2 negative patient......in front line!   a 7 months improvement was reported (20 Vs 13 months).  BOLERO-3 is talking!

Saturday, January 24, 2015

Cytokines and Vitamin D mysterious interaction...is there a value in Cancers of the elderly!

"These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins could induce substancial intramonocyte killing of M.Tuberculosis.   The mechanism involved in this killing activity is not clarified"

From M.Denis.
"Conclusions: our data imply that specific actions of 1,25 (OH) Vitamin D3 in Cytokine stimulated T-Cell functions could have a role in preventing T cells related autoimmune diseases but also predispose toward T-cell mediated allergic reactions"


        Ralph Thien  et al   (J Allergy Clin Immunol 2005;116:683-9.
 
 
F Focus on Iron,Selenium, Cupper, and Zinc
   Vitamin A  (mortality to infections),B (impacts on number of lymphocytes),C(phagocytosis),D(susceptibility in IL-6 
    diseases) ,E (dysfunction of T&B cells)   (Read Susanna Cunnigham-Rundles et al.

   When the age comes!
 

Don't do it again in NSCL Cancers

Clinically Negative phase III trials with Antiangiogenics (and their targets) in NSCL cancers:

1.Thalidomid  -----an Antiangiogenic drug
2.Cediranib---------VEGFR TKI
3.Vandetanib--------Multikinase TKI
4.Sorafenib---------Multikinase TKI
5.Sunitinib----------Multikinase TKI
6.Aflibercept------------VEGF/PIGF

(from C.Langer notes)

Wednesday, January 14, 2015

Castleman disease

for Castleman disease
Hepcidin, Arlet at al" The results of this unique case study (1) explain the mechanism of iron deficiency observed in some children with CD, (2) confirm in vivo the regulatory effect of IL-6 in human hepcidin production, and (3) suggest that iron deficiency is a causal link between IL-6 and anemia of chronic disease."
from conference correspodent:
Siltuximab Efficacy in Multicentric Castleman's Disease Is Independent of Baseline Symptom Burden
Multicentric Castleman's Disease (MCD) is a rare, highly symptomatic, systemic lymphoproliferative disorder driven by dysregulated interleukin (IL)-6 signaling

from Johnson :"
Fifty-three patients were randomized to the SYLVANT arm at a dose of 11 mg/kg and 26 patients were randomized to the placebo arm. Patients had symptomatic MCD and were HIV negative and HHV-8 negative.[1] In this pivotal study, which led to the FDA approval, more than one-third of patients in the SYLVANT arm had a durable tumor and symptomatic response to treatment plus best supportive care (BSC), compared to none of the patients who received placebo plus BSC (34 percent versus 0 percent; 95 percent CI: 11.1, 54.8; p=0.0012). A durable response was defined as tumor and symptomatic response (reduction in tumor size and disease symptoms) that persisted for a minimum of 18 weeks without treatment failure."
The FDA approved the drug based on these findings

A trial of Dexamethasone and Rituxan could also be given....

Saturday, January 3, 2015

about Vitamin D

Dr David Samadi:
"A University of Colorado Cancer Center study recently published in the journal Prostate presents new evidence that vitamin D may help reduce cancer-causing inflammation. Scientists found that the gene GDF-15 – known to be up-regulated by vitamin D - can help block a protein which stimulates tumor growth." (suppression of the NFkB?)

from WebMD:

" The pigment melanin reduces the skin's ability to make vitamin D in response to sunlight exposure. Some studies show that older adults with darker skin are at high risk of vitamin D deficiency."

Is this why Prostate cancer tend to be more aggressive in Black
Is this sufficient evidence that Vitamin D deficiency should be avoided to reduce cancer
what is the role of Vitamin D in reducing certain Cytokines
does Vitamin D deficiency play a role in other cancers?
what is the role of Vitamin D in altering the Telomeres?
should Vitamin D enter the main stay of treatment of Metastatic Prostate cancers  (particularly in black)

While the NFkB may be involved, the truth is  everything  seems to happen at the Vitamin D receptor .
We know that in certain cases of deficiency (induced by Cytokines), the cell will increase the receptors to maximize its chances of capturing the Vitamin. And this may be the first move to neoplastic transformation.   Indeed increase in unbound Receptors of Vitamin D will overactivate not only the WNT but the deadly Hedgehog signaling changing the shape of the the prostate and its fate or life.   Just the BAG-1 (BCL-2 interaction) stimulation that will ensue is sufficient to beat the drum of Neoplasia.    Subsequent disruptions including  of Cav3, Raf, the RUNX and so forth will ensue.  Leading to a full fledged prostate cancer....by the way this receptor also interacts with the AR (Androgen Receptor).     Avoid Vitamin D deficiency by all costs!  (The scenario where desensitization of Vitamin D receptor is the alternative is not discussed here)