Thursday, November 27, 2014

#Throwback Thurday/Thanksgiving!!!!

When I say I've been cooking forever, I'm not kidding!!!  I was three in this pic and I still love me some pie!!!
If you want to make your own pie dough, be my guest...but unless I'm making a tart that is savory or one that needs to stand up to special flavors, I just roll with the store bought version...though I am partial to this style.
Roll it out a little more after a sprinkle of flour.... 
And place it in your dish...
For any berry pie...the basic recipe is:  3 cups berries, 4 tablespoons flour, 2/3-1 cup sugar depending on taste and sweetness of your berries, butter to dot over the top of the fruit...and your pastry.  I do like to add some lemon zest to blueberries or blackberries as you see here.  Nutmeg and cinnamon are nice additions with peaches and apples.
Mix.  Then place fruit mixture in your pastry lined dish.  Use a brush or your finger to dampen your pastry edge with water...that will be your 'glue' when you put on either a solid pastry "lid" or the lattice top shown below....
For a lattice top, roll out the other half of your dough as you did for the bottom, but afterwards, cut into strips.
Choose strips of appropriate lengths and smish their top edge into your water dampened edge of the bottom pastry. 
You could just lay pieces across one way and then across in the other, but I think it is fun to actually layer mine in an alternating fashion!!! 
After you have finished creating the lattice with your strips, make sure all ends are pressed into the sides of the bottom layer of pastry.  Trim off excess by running a knife around the edge of your dish and crimp it all together using your fingers or mash with the tines of a fork. AND....if you're like me and tend to forget to dot your top with butter...you can always squich it in the spaces between your lattice!  Handy, right?
You can then bake in a 400 degree oven for about 40-50 minutes, until the filling is bubbling and the pastry nicely browned, as is.  But it does protect the crust on the outer edge from getting too browned if you place a little foil collar around the edge.  You can remove it, oh around the last 10 minutes of cooking.  And using a brush to apply a little milk or egg wash to the pastry edges makes them shiny and a bit more tasty, especially if you add a sprinkle of sugar or cinnamon sugar like a special glitter topping! If you want a solid top to your pie - just lay that pastry piece on top and attach and finish the edges per previous instructions.  Do remember to add some slits (as simple or as fancy as you like) to provide vents for the steam...else-wise your pie might suffer a blow out!
No matter the style pie you choose, there will always be a little remnant of dough.  Ball it all back together, roll it out and make a tart!!! 
Fill with raisins and cinnamon sugar, blueberries and lemon curd, or any preserves you have on hand, dot with butter, fold over! 
Press edges together after they are dampened with water, crimp, and make your poke holes. 
After baking with the big pie for oh, about 15-20 minutes, depending on how big, thick or the sort of filling you put in...you now have a snack to enjoy ahead of time or a little tart for breakfast! 
Ta dah!!!!  
Enjoy!!!  Happy Thanksgiving.  May there always be pie!!!  Love - c

Tuesday, November 25, 2014

For Kim...

Yup!!!  Surprised you didn't I?  Just wanted to let you know that I appreciate your reading of my meanderings, laughing at my jokes, passing over things that don't mean that much to you...yet coming back for more on another day, and sharing YOUR thoughts about MY thoughts!!!  THAT is a gift my friend!  A real gift.   I appreciate it and you...everyday.

I know there are many other faithful readers out there.  Some of you come here to find the information you need about melanoma for yourself or your loved one.  Some of you read because of an interest in me.  Some people land here for rather strange reasons....like google-ing "Black Silky Chicken" (been there, done that myself...hope my recipe helped cause there ain't that much out there on that one!!!!) and recently "another form of Botox"!  I'm sure my suggestion that the 'numbing' process for the halo application was the new wave in beauty treatments didn't help!  Or, at least I hope it didn't!!!

There are those whose role in my life would imply that they SHOULD read and comment, but purposefully choose not to.  I could focus on that.  It is rather bizarre, overwhelming, and sad.  But, to focus on that would do no good.  It would also negate all the beauty that has come my way because of those who choose to share...their lives...with me...the good and the hard.  Jonathan and Francoise, Lucy and Sue, Elaine, PJ, Eric, Steven, Jeanne....and so many more.  Friends from afar, now friends in my heart.  There are friends of my youth..now dear again....Terrie, Terri, David and the rest of you...reconnected...making me whole.

And, there are those of you I will never know...almost 150,000 peeks all together....from all over the U.S., the U.K., France, Turkey, China, Russia, Ukraine, Canada, Australia, Belgium, Germany, Spain, Netherlands, Finland, Poland, India...I wish you well.  I hope I helped.  I hope you smiled.

There are my faithful soldiers.  My rocks.  My battalion.  Ready at a moment's notice.  Your love, the armor you provide....immeasurable.  There are no words.  

So, Kim.  You make my work load lighter.  You make my day brighter.

Happy Thanksgiving.  For Kim...and all of you...I am thankful.  Love - c

Saturday, November 22, 2014

Data on BRAFi combo's and effects of ipi before and after


Combined Vermurafenib and Cobimetinib in BRAF-Mutated Melanoma. 
Dreno, Atkinson, et al.  N Engl J Med 2014 September

Phase 3 study.  495 patients, previously untreated with unresectable BRAF V600 mutated melanoma got either vemurafenib and cobimetinib or vermurafenib and placebo.



Vermurafenib and Cobimetinib
Vermurafenib and placebo
Progression free survival
                 9.9 months
                  6.2 months
Complete or partial response
                 68%
                  45%
Complete response
                 10%
                  4%
Overall survival at 9 months
                 81%
                  73%


Combined BRAF and MEK inhibition versus BRAF inhibition alone in Melanoma.
Long, Stryakoviskiy, et al.  N Engl J Med.  2014 September.

Phase 3 trial.  423 BRAF V600 of V600K mutation melanoma patients with unresectable Stage IIIC or  Stage IV disease.




Dabrafenib and Trametinib
Dabrafenib and placebo
Progression free survival
                 9.3 months
                  8.8 months
Overall response at 6 months
                 93%
                  85%
Overall response rate
                 67%
                  51%
Fever
                 51%
                  28%
 

Combined Dabrafenib and Trametinib in patients with BRAFV600 mutant melanoma experiencing progression with single-agent BRAF inhibitor.
Johnson, Flaherty, Weber, Infante, Kim, Hamid, Sznol, Sosman, Daud, et al. J Clin Onc, 2014 Oct

Phase I/II study.   Group B = 26 patients treated with dabrafenib and trametinib after disease progression with BRAFi before study enrollment.  Group C = 45 patients treated with dabrafenib and trametinib after progression on dabrafenib monotherapy as cross over treatment.




Group B
Group C
Overall response rate
                 15%
                  13%
Progression free survival
Treated with Dabrafenib less than 6 months – 3.9 months
Treated with Dabrafenib more than 6 months – 1.8 months
      3.6 months
Overall survival
Tx more than 6 months – 26%
Tx less than 6 months – 0%
      11.8 months




Conclusion:  Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF i resistant melanoma.  This may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy for more than 6 months but demonstrated minimal efficacy after rapid progression with BRAFi therapy.

Characteristics of pyrexia in BRAFV600E/K metastatic melanoma patients treated with combined dabrafenib and trametinib in phase 1/2 clinical trial.  Menzies, Ashworth, Flaherty, Weber, Infante, Hamid, Sosman, Daud, et al.  Ann Oncol. 2014 November

Pyrexia = fever, in this case defined as a temperature at or greater than 100.4 or related symptoms.
59% of patients developed pyrexia.  24% had symptoms with recorded increased temp.  Median onset of first pyrexia was in 19 days, median duration of 9 days.  Pyrexia patients had a median of two pyrexia events, but 21% had three or more events.  No baseline features predicted pyrexia and it was not associated with clinical outcome.

Objective responses can be obtained by CTLA-4 inhibition in metastatic melanoma after BRAF inhibitor failure.  Schreuer, Chevolet, et al.  Melanoma Research.  2014 November

64 patients with unresectable Stage III/IV BRAF V600 mutant melanoma.  33 had been treated with BRAFi before ipi.  31 patients were treated with ipi first.  In BRAFi first patients:  three complete responses and 6 partial responses, with median overall survival of 10 months from start of ipi therapy.  Ipi first patients:  no complete responses and 4 partial responses, with median overall survival from start of ipi therapy was 12.3 months.  Response rate did not differ significantly between the groups.

So....not really new news.  Combo's offer better results.  Fever occurs often and can be worse in the combos, but no patient specific features can predict who develops fevers and fever has not been associated with outcome, for better or worse.  In the final study, for all their numbers, there was apparently no statistical difference in response whether you took BRAFi followed by ipi or vice versa.  Best wishes - c

Tuesday, November 18, 2014

I'll stand by you....

For all of you who have been there for me...  For those who have no one with whom to stand....I'll stand by you.

The Pretenders, I'll stand by you...

Oh, why you look so sad?  Tears are in your eyes. Come on and come to me, now.  Don't, be ashamed to cry.  Let me see you through, 'cause I've seen the dark side, too.

When the night falls on you, and you don't know what to do.  Nothin' you confess, could make me love you less. I'll stand by you.  I'll stand by you.  Won't let nobody hurt you, I'll stand by you.

So, if you're mad...get mad.  Don't hold it all inside, come on and talk to me now.  Hey, what you got to hide?  I get angry, too.  Well, I'm a lot, like you.

When you're standing at the crossroads, and don't know which path to choose, let me come along.  Cause, even if you're wrong....

I'll stand by you.  I'll stand by you.  Won't let nobody hurt you.  I'll stand by you. Take me in, into your darkest hour.  And I'll never desert you.  I'll stand by you.


And when, when the night falls on you, baby - You're feeling all alone.  You won't be on your own.
I'll stand by you.  I'll stand by you.  Won't let nobody hurt you.  I'll stand by you.  Take me in, into your darkest hour.  And I'll never desert you.  I'll stand by you.

For all my loves...those I've just met...those who know me well and are my circle of support...those I've known from their first breath....I'll stand by you.  Always.  No matter what.  No matter how far you may think I am.  I am here...always...for you.

Love -c

Saturday, November 15, 2014

Commentary - Why checkpoint inhibitors need help and a little push for SCIB1

Commentary by Richard Goodfellow, June 2014, Scancell

Despite all the advances in melanoma treatments in the past 4 years, we're still not quite there yet!  I thought this essay was interesting...though you must keep in mind that the author is the chief executive officer of the company that makes SCIB1.  However, Bent has always held that dendritic cells will prove essential in really understanding and treating melanoma.

Excerpts:  "Checkpoint inhibitors enable the host immune system to resume its ability to recognize, attack, and destroy cancer cells.  Ipilimumab was the first.  Drugs blocking PD-1 and its ligand PD-L1 are in advanced trials.  However, checkpoint inhibitors cannot work...if the patient fails to mount an adequate immune response or if the tumor evolves so that is it no longer recognized by the pre-existing immune response."

"[Anti-] PD-1 drugs are being combined with ipi, tyrosine kinase inhibitors (sunitinib and erlotinib); with anti-CD27 antibody varlilumab; and BRAFi [to try to answer the lack] though side effects are often an issue with these combos."

"Taking the brake off T cells with checkpoint inhibitors whilst simultaneously pressing the accelerator using active immunotherapies is a logical next step...  Vaccines can stimulate 'de novo' immune responses, but until recently, none of the vaccines...have been able to produce potent T cells with the power and specificity to recognize and kill tumor cells.  Peptides and MAGE vaccines failed to show any advantage.  A phase 3 study of a virus encoding GM-CSF has shown  some promising results, but the patient must have accessible tumors."

"We would argue that this advantage can be obtained by using the power of dendritic cells, the 'generals of the immune response army'.  Our first product, SCIB1, is a DNA plasmid encoding an antibody with four melanoma-specific T cell epitopes grafted into its structures.  We use eletroporation (the use of electrical fields to increase DNA drug delivery efficiency by up to 1000 fold compared to conventional injection) in conjunction with IM injection to deliver SCIB1 to patients.  This results in the direct uptake of DNA into cells and also enhances the immune response by targeting the expressed hybrid antibody to dendritic cells via the CD64 receptor."

"Data from a Phase 1/2 clinical trial of SCIB1 in patients with advanced melanoma has shown high immune response rates, evidence of prolonged survival and tumor destruction with a benign side effect profile.  Median survival time in patients with Stage III/IV disease is now 30 months since patients entered the study.  Patients with resected Stage IV disease are all still alive 19-41 months since tumor removal.  This compares favorably with published survival rates for patients with resected disease where 50% of Stage IV patients usually die within 21 months of surgery."

Hmmm...  I haven't seen any published research data for SCIB1 yet.  Most of the pr...IS pr...being put out by the company or other pharma investments firms.  But....the trial is real, though only in the UK at this time...here's the link:

Link to clinical trial with SCIB1  

Would love for this to hold the key!  We'll see what happens! - c


Thursday, November 13, 2014

Skin stuff with Anti-PD1

I have certainly had weird skin things during and after being on Nivo!!!  Of course weird skin thing numero uno was melanoma!!!  Much as we have with ipi, as more folks take the anti-PD1 drugs, we will find out even more things about their side effects and how to deal with them.


Lichenoid dermatitis in two patients with metastatic melanoma treated with anti-PD1 therapy.
Joseph, Goedjen, Gordon, et al.  Cancer Immunol Res. 2014 Oct 6.

The "two most common side effects of anti-PD1/PDL1 therapies include rash and [itching] occurring in about 20% of patients.  While the rash is generally attributed to be immune mediated, the exact mechanisms of the rash remain unclear....We report two cases of lichenoid dermatitis [A scaly, itchy rash...resembling eczema or psoriasis and can be purplish in color.]  in two patients treated with MK-3475 that were characterized with marked T-cell infiltrates with few PD-1 positive cells.  Both patients were taking lisinopril [An ACE inhibitor used to treated increased blood pressure and congestive heart failure.], an agent associated with lichenoid reactions, however, neither had a rash prior to starting MK-3475. Both rashes were relatively mild allowing treatment to continue and responded to topical steroids.

Yours, c

Tuesday, November 11, 2014

Just for fun...crazy wonderful skirts!!!

I made some rather simple summer dresses, but decided to jazz things up with some crazy skirts!!!

Loved this material so much (Though there were those who said, as I proudly displayed this material after purchase, "You would never wear that!" How wrong they were. How little they know me!) that I had the bright idea to widen the A of the a-line skirt pattern I was using!!

Turns out, I am NOT ready for drafting my own patterns!!!  I looked like a puff butt oompa-loompa!!!!  But (no pun intended) after adding a pleat on either side, per Rosie's advice, I calmed the bubble!!!  Another sad fact.  I worked REALLY hard to match these polka dots!!!  Hmmm......

Have some minor concerns about the appearance of some sort of dinosaur tail (Is it a stegosaurus???) going up the rear.....but, what's a girl to do?  On the good side....it is stitched together beautifully (if I say so myself!!!) with completely finished insides and I am really happy with the end product.  Also on the good side...though not at the time!!!  My serger ran out of thread in one bobbin in the middle of this production...thereby FORCING ME...yes, forcing...me to learn to thread the sucker...which...I did...so YAY!

Simple A-line (the pattern I probably should have stuck with!!!) but done up in wonderful wines of the world!  And, YES!!!  The sides and rear line up perfectly on this one!!!  I told B this one was perfect for a trip to France...or a wine tasting party at the very least!!!
Sante'! -c