Monday, June 17, 2019

Sew Chaotically! ~ Romero trousers (shorts) for a purple durple!

With these trousers and an ancient pair of J Crew sailor pants as inspo, I wanted to make a pair!  Searching for an appropriate pattern I discovered The Romero Trousers by Pauline Alice.  Before I could get started, Rosie spied it and a couple of summer shorts for her jumped to the start of the sewing que.  This pattern is AWESOME!!!!!  I have complicated it a bit by using duck, but it was the best choice to get the look, in vivid color, that she was going for.  I have stitched up a 40, but with about an inch off the hem, 1/2 inch rather than the 5/8 inch side seams and small wedges out of the center back and side seams fading to nothing in about 4 inches.

The pattern stitches together perfectly and has a really ingenious way of dealing with the pocket and front piece.  I admit the written instructions hurt my head a little, but the great video (linked above) shows how to do it easy peasy.  I couldn't resist some serious  pocket love!
Aren't they the cutest??????
I used the straight waist band as prescribed and it stands away from the body just a bit.  On her next pair, already in process, I am using a self drafted curved band on that bit!  We'll see how it goes!
My girl is the best!  Aren't her flowers pretty?
Thanks to birthdays and Father's days...this week has blessed me with lots of fun with my peeps!  I got to visit with Fred-o a couple of days ago and yesterday I got to hang out with my purple durples!!!  Yes, it is like living life with stereo speakers as since Roo's been able to talk, I have heard the exact same words come out of these two, simultaneously when together, but also even when they are apart!!!  Yes, they are goof balls!  No, I wouldn't have it any other way!!!

Yep.  She's wearing a Sorbetto Top by Colette.  Her summer staple!

Live, love and sew ~ chaotically!!! - les

Friday, June 14, 2019

Sew Chaotically! ~ I jumped! On the jumpsuit bandwagon!!

When I scooped up this lovely salmon pink linen at Fine Fabrics in Atlanta, I had every intention of making an apron dress along the lines of this lovely one by Pip-Squeak Chapeau Etc...

Then I saw these amazing jumpsuits!!  I had vowed not to jump on the jumpsuit bandwagon, but these are so cute!!!  Suddenly, I remembered I had this pattern!!!  I actually made one of these for myself in the 80's!!  For realz!  While I would have much preferred a looser version with sleeves, I didn't have the yardage. Still, I decided I could make it work!
I managed to get the sleeveless, cropped leg version out of my fabric, stitching it up with no problems.  But the look of the "sleeves" made me fear it was turning out more like a "Dynasty" costume than a chic modern jumpsuit!
 I considered just trimming and hemming.  But, I slept on it.
The next day, I stumbled upon this and thought - I like it!  I could do that!!  Maybe....
Starting with some mad basting...

... I achieved this!
I think it worked!
...or belted and cuffed!

I'm pleased with my jumpsuit and think it will get lots of fun use.  In the background, you see my beautiful wild azaleas that bloom every year just in time for Fred-o's special day. And today...

...I enjoyed a lovely visit with these handsome boys!!!
I'm glad I jumped! I'm especially glad to have my sweet punkins in my life and super blessed when I get to spend time with them!  Live, love and sew chaotically! ~ les

Monday, June 10, 2019

Why doesn't immunotherapy work for all melanoma patients?

WHY?????  And what should we do when it fails?  Dismaying questions with no clear answers, right?  But, researchers are working on them!

First - what to do when immunotherapy fails?

What to Do When Anti-PD-1 Therapy Fails in Patients With Melanoma.  Mooradian, Sullivan.  Oncology, April 2019.

Monotherapy with immune checkpoint inhibitors, specifically those targeting programmed death 1 (PD-1), has revolutionized the treatment of metastatic melanoma: approximately 40% of patients achieve a partial or complete response, many of which are durable. However, a subset of patients who initially respond to therapy will progress, leaving the majority of patients in need of an effective second-line approach. While some standard therapies exist, there has been robust interest in utilizing targeted immunotherapy combinations in this population to overcome primary or acquired resistance. Other approaches include treatment with anti-PD-1 agents beyond progression; targeting oligometastatic disease with surgery, radiation, and/or intratumor injections; and the use of other approved systemic therapies. This review summarizes the current available treatment strategies for patients with advanced melanoma when PD-1-directed therapy is not enough.

You should be able to get the entire article via this link:

Note:  We already know that combining ipi with anti-PD-1 provides improved response rates as compared to anti-PD-1 as monotherapy, though for some, even that is not enough.  Here is a primer of basic melanoma treatments I put together that covers some of the treatments described above:
Melanoma Intel: A primer for current standard of care and treatment options

But, back to the first question ~ as Fierce Biotech put it in their article linked here:  What causes immuno-oncology drug resistance? 2 research teams uncover clues

The article notes: 

Checkpoint-inhibiting drugs have revolutionized the treatment of melanoma and other cancers by freeing up the immune system to attack tumors. But the medicines don’t work for as many as half of patients, even when they’re combined with other cancer treatments.
Now, two separate research groups have uncovered different mechanisms of immuno-oncology drug resistance. One involves the gut microbiome, while the other is related to vesicles that are produced by cancer cells.

First, a worldwide consortium of 40 scientists led by Sanford Burnham Prebys released a study demonstrating that the gut microbiome orchestrates the immune system’s response to cancer. They published their observations in the journal Nature Communications.  The Sanford Burnham Prebys-led team made the discovery by working with mice engineered to lack RING finger protein 5 (RNF5), a gene that normally works to clear damaged proteins from cells. These mice mounted a strong immune response to melanoma, so the researchers used bioinformatics technology to identify 11 bacterial strains that were plentiful in the animals’ guts. They then transferred the bacteria to normal mice and found it also induced a strong immune response to melanoma in those animals.  The researchers mapped out the immune components that were active in the gut, and they discovered that a signaling pathway called the unfolded protein response (UPR) was reduced when immune cells were activated. Then they studied tumor samples from people who had received checkpoint inhibitors, and they found reduced UPR expression correlated with a good response to treatment. 

The findings “identify a collection of bacterial strains that could turn on anti-tumor immunity and biomarkers that could be used to stratify people with melanoma for treatment with select checkpoint inhibitors," said senior author and Sanford Burnham Prebys professor Ze'ev Ronai, Ph.D...

The second study, from a team at the University of California, San Francisco (UCSF), focused on the protein PD-L1, the target of some checkpoint-inhibiting drugs. Normally, checkpoint inhibitors work by recognizing PD-L1 on the surface of cancer cells and then interfering either with it or the related protein PD-1. The UCSF researchers discovered that in some patients, PD-L1 travels throughout the body, inhibiting immune cells before they can reach the cancer.

In those patients, the PD-L1 ends up in exosomes, which are vesicles that come from cancer cells and travel in the bloodstream to the lymph nodes, the UCSF team discovered. While there, they “disarm” the immune cells, so they’re unable to launch an attack against the cancer. They published their findings in the journal Cell.  The prevailing view of why patients sometimes don’t respond to PD-L1 inhibitors is that their cancers are not making enough of the protein. But the UCSF researchers showed "the protein was in fact being made at some point, and that it wasn't being degraded,” senior author Robert Blelloch, M.D,. Ph.D.... said... “That's when we looked at exosomes and found the missing PD-L1."  In a second experiment, the UCSF team used the gene-editing technology CRISPR to delete two genes necessary for exosome production from cancer cells. Mice that received those cells had more activated immune cells in their lymph nodes than did animals that got unedited cancer cells.  They then treated a mouse model of colorectal cancer with a combination of a PD-L1 inhibitor and a drug that prevents exosomes from forming. Those mice survived longer than animals treated with either drug alone did.  Blelloch’s team plans to conduct further studies, with the ultimate goal of developing a “tumor cell vaccine” to help patients who don’t currently respond to checkpoint inhibitors.

SO...two very different things are addressed within this article....
1.  The cooties in our gut make a difference.  I've been writing about this for some time.   Here is a recent report with links to many more within:  DECREASED progression free survival in melanoma patients treated with antibiotics prior to or at start of immunotherapy!!!!    Side note:  Additional studies show that you have to consume the real deal.  Probiotics out of a bottle won't do the trick.  In fact, attaining your cooties that way may actually DECREASE your response to immunotherapy.
2.  The whole PD-L1 positive vs NOT positive thing!  We have long known that having PD-L1 positive tumors does not guarantee a response.  AND... folks with tumors NEGATIVE for PD-L1 can still sometimes gain one!  Here are a bunch of reports addressing the PD-L1 conundrum!

There is also this report on the same research in the NY Times from April: Cancer’s Trick for Dodging the Immune System, where the author notes:

Cancer immunotherapy drugs, which spur the body’s own immune system to attack tumors, hold great promise but still fail many patients. New research may help explain why some cancers elude the new class of therapies, and offer some clues to a solution.  The study, published on Thursday in the journal Cell, focuses on colorectal and prostate cancer. These are among the cancers that seem largely impervious to a key mechanism of immunotherapy drugs.  The drugs block a signal that tumors send to stymie the immune system. That signal gets sent via a particular molecule that is found on the surface of some tumor cells.  The trouble is that the molecule, called PD-L1, does not appear on the surface of all tumors, and in those cases, the drugs have trouble interfering with the signal sent by the cancer.  The new study is part of a growing body of research that suggests that even when tumors don’t have this PD-L1 molecule on their surfaces, they are still using the molecule to trick the immune system.  Instead of appearing on the surface, the molecule is released by the tumor into the body, where it travels to immune system hubs, the lymph nodes, and tricks the cells that congregate there.
“They inhibit the activation of immune cells remotely,” said Dr. Robert Blelloch, associate chairman of the department of urology at the University of California, San Francisco, and a senior author of the new paper.  The U.C.S.F. scientists discovered that they could cure a mouse of prostate cancer if they removed the PD-L1 that was leaving the tumor and traveling to the lymph nodes to trick the immune system. When that happened, the immune system attacked the cancer effectively.
Furthermore, the immune system of the same mouse seemed able to attack a tumor later even when the drifting PD-L1 was reintroduced. This suggested to Dr. Blelloch that it might be possible to train the immune system to recognize a tumor much the way a vaccine can train an immune system to recognize a virus.  The work was done not in humans but in laboratory experiments and in mice, and it is not clear whether the results will translate in people. Dr. Ira Mellman, vice president of cancer immunology at Genentech, called the findings “a most interesting result.”  “But as with all mouse experiments, you get insight into basic mechanisms, but how it translates to the human therapeutic setting is unclear,” said Dr. Mellman. He is skeptical, he said, but plans to meet shortly with Dr. Blelloch to discuss the implications of the work.  The new research dovetails with other recent studies, including a paper published last year in the journal Nature that showed that PD-L1 molecules released from skin cancer tumors can suppress the body’s immune function.  When these bits of PD-L1 travel outside the cell, they are known as exosomal, and the discovery of their role is one of many fast-moving developments refining an area of medicine that has become among the most promising in decades.
Late last year, the Nobel Prize was awarded to two scientists — James P. Allison of the M.D. Anderson Cancer Center in Houston, and Tasuku Honjo of Kyoto University in Japan — who did groundbreaking work in immunotherapy.  An explosion of additional research is aimed not only at refining the therapies — which can have profound side effects — but also at searching for other molecules involved in the perilous dance between cancer and the immune system.  Far more study is needed. But Dr. Blelloch said the findings have him looking for ways to take the next steps into turning the discovery into a concrete therapy.  Interfering with the PD-L1 traveling to lymph nodes “can lead to a long-lasting, systemic, anti-tumor immunity,” the paper concluded.
While this research leaves us with plenty of unanswered is the first in a long while that begins to answer the PD-L1 conundrum!!!    Here's a link to a related article from Nature if you like to read all the science for yourself:  Exosomal PD-L1 Contributes to Immunosuppression and is Associated with anti-PD-1 Response  
Hopefully, more complete answers and treatment solutions will be developed SOON!!!  Hang in there, ratties! - c  

Thursday, June 6, 2019

Sew Chaotically! ~ REFASHION!!! Skirt to Nikko and dress to useful separates

I had a fun and productive Me Made May!!  Thanks for tolerating all the pics.  Not sure how effective May as Melanoma Awareness Month is ~ at least in this forum as I am probably simply singing to the choir!  Anyhow, I made some things I really like (a couple yet to be photographed and published) and embraced making the things in my closet be useful.  Some found new homes and some were refashioned!  This skirt has been worn a bit, but the waist band was always too big, despite having been taken in years ago.  Plus, who REALLY wants a bunch of extra fabric scrunched around your waist?  Clearly didn't think that through when I bought it!  Still, it was made of a lovely soft knit.  So, what to do????   A Nikko top refashion!

Since my two prior Nikko's pulled just a bit across the front, I cut the front piece of this one a half inch away from the fold and lengthened the neckband accordingly.  This fabric is so soft if may not have been necessary - but it worked!
A cute useful piece for my wardrobe from a little worn garment!  Plus, the scraps will go in my "pouf bag" and the elastic will find a use somewhere!
Rose is gradually working on her annual wardrobe eval and wondered what could be done with a slightly frumpy, over sized dress whose fabric she liked and is in perfect condition.

Easy!!  Hack it in two! Leaving the elastic intact, serge the 1 inch edge of the bodice left on above the casing, fold over, then hand stitch it behind the elastic, with carriers replaced for a lovely skirt!
For a little crop top, serge and hem the bottom.  Add a pleat to the back to improve the fit!  Tadah!!! An unused piece now useful in sooooo many ways....
Add a different cropped tee and tie in back for a cute outfit for errands.
Add skinny jeans and your dancing shoes for a night out!
Tie it conventionally like Mannie or go full boho chic like Roo!
I used to loathe mending and adjusting existing garments, but I now find the ability to make rtw garments into more useful, well loved pieces very satisfying!!  Getting to play with my girl is an added bonus!  (And, yes.  My take on what's coming out of ASCO is on the way.) Meanwhile ~ Sew and live chaotically!! ~ les

Tuesday, May 28, 2019

Sew Chaotically! ~ Me Made May Days 25, 26, 27 and today - a pretty blouse

To catch up...
Me Made May Day 25!  Bit of a repeat, but I love this versatile Peppermint Peplum Top by In The Folds so much this may be how summer rolls!  My photog cracks me up!!!
Me Made May Day 26! Love this breezy African Wax Print Inari top.  Will probably make it a smidge longer next time.
Me Made May Day 27!  This Polly top, one of several I've made, is perfect in hot weather!  I made this one using a remnant of a baby gingham I had on hand and a past its prime fine knit sweater!
 And for Me Made May TODAY:  a bit of a cheat.  Having spent the day "cleaning the forest" as the kids used to say when I went after the Virginia Creeper and such in the wooded areas we have on our property with my weed eater, I figured that was an "outfit" that needed no documentation!!!  BUT ~ I made this pretty little top at the end of April to wear to Char's wedding where it was lovely, easy to wear and great for partying with the sisters!!!
You gotta love Sister Sledge!!!  Bahaha!!!

Anyhow, I thought today I'd share it!  It started with this pretty, sheer crepe I got in Walthamstow Market during our London trip!  Only two pieces of that haul remain unused!  When I saw the dress Ruthie was going to wear and learned that the guys would be wearing khakis, I knew the perfect outfit for the event.  This fabric, made up in a pussy bow top using  (B6578 made previously here sans bow!) paired with these perfect pants (B6178)!!!

I used French seams throughout.  Added a narrow elastic to the sleeves.  And I think it turned out really well.  Better, in some ways, than the one made previously in the Liberty Print as this fabric drapes so softly.

Isn't it pretty?
And continue our Melanoma Awareness PSA...

Not all melanoma is due to tanning.  But, your odds of acquiring melanoma, not to mention other skin cancers, age spots, and wrinkles, sure increase when you do!!!  Just say'n!!!! Live and sew chaotically! ~ les

Friday, May 24, 2019

Sew Chaotically! ~ Cute linen top and refashioned skirt! A message about scars.

Recently I've embraced going through my stash, utilizing ALL bits and bobs, rethinking patterns into new uses without buying more, completing planned projects, and filling some holes in my wardrobe.  I've added needed robes and gowns.  Found ways to utilize scraps (from seam binding to pouf-to-be stuffing, to tops for play) and refashion unused items into more useful pieces.  This outfit ticks a couple of those boxes!!!

From these two patterns, the one on the left given to me from a friend who had been gifted it from another, and an old a-line skirt pattern I've used a zillion times, along with....

...some green floral print quilting cotton from a "play sack dress" when I was pregnant, lactating and chasing small children that I haven't worn in YEARS, but had saved because the fabric was pretty, combined with a bit of fabric purchased for what purpose I know not....back when Roo was about 4 years old...used only to make a little apron for her at one point ~ I made this!!!!

A light weight linen blend with beautiful drape, probably from the now defunct Hancock's Fabric.

Loving my roses, brought to one part of my yard from my childhood home many years ago with a sprig planted along this trellis last year.  Skirt made with already existing slits in the material cause I had to...and...I like it!!
Ta-dah! Useful pieces that can be happily worn in lots of combo's from 'worthless' remnants!
Continuing May's Melanoma Awareness ~ just as pretty outfits can be created from things that are scarred and could easily be tossed in the bin as ruined, marred, no longer of use ~ so can a beautiful life...

Or as I put it SCARS are more than skin deep. The love that sees me through....

And there is this beautiful paragraph from: Little Bee, by Chris Cleave

"On the girl's brown legs there were many small white scars. I was thinking, Do those scars cover the whole of you, like the stars and the moons on your dress? I thought that would be pretty too, and I ask you right here please to agree with me that a scar is never ugly. That is what the scar makers want us to think. But you and I, we must make an agreement to defy them. We must see all scars as beauty. Okay? This will be our secret. Because take it from me, a scar does not form on the dying. A scar means, I survived."

Live and sew chaotically! Scars and all.  ~ les

Thursday, May 23, 2019

Sew Chaotically! ~ Me Made May and Melanoma Awareness! Days 21, 22, 23!

Ain't brushed my hair.  No time to care, with a bit of bean picking in a cool little me made shift!!  McCall's 6074.  Technically designed for a knit.  But it worked out with no need for the elastic under the bust in this cool cotton eyelet. 
May 22!
Cool comfort for the win in seersucker. Butterick's 5890 fit and flare top.  Really recommend.  It's a really great fit and easy to make!
May 21
Navy throw.
I love to crochet, but usually in the winter, when you have the desire to snuggle under a blanket but look productive at the same time!!  Have been working on this little throw over the past few months while sitting with a convalescing friend.  With only the last row to go, decided to finish it off this morning.  It is part of a sitting room overhaul that is not yet complete but has everything to do with these yet to be finished sashiko embroidered pillow covers....
Scott boy stoked about it, despite my procrastination!!!
May's Melanoma Awareness Message ~
It's ALL that!!!  Live and sew and grow and play chaotically! ~ les