The Mental Price of Melanoma

Given the many pleas and posts and requests for help that I've seen or have been sent directly regarding stress and worries and fears when peeps are given the diagnosis of melanoma....I thought the first article might demonstrate that you are not alone, though most folks diagnosed with melanoma have a "very good prognosis" (See?  I'm not the ONLY person saying that!!!) and the approach spelled out in the second might provide some useful information - 

Fear of new or recurrent melanoma after treatment for localised melanoma. Bell, Mehta, Turner, et al. Psychooncology. 2017 Jan 4.  

To estimate the amount of fear of new or recurrent melanoma among people treated for localized melanoma in an Australian specialist centre.  We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores.  215 people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was was 15. A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores greater or = to 13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores greater or = to 6). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma.  There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis.


Psychoeducational Intervention to Reduce Fear of Cancer Recurrence in People at High Risk of Developing Another Primary Melanoma: Results of a Randomized Controlled Trial. Dieng, Butow, Costa, et al. J Clin Oncol. 2016 Dec 20.   

People with a history of melanoma commonly report a fear of cancer recurrence (FCR), yet psychologic support is not routinely offered as part of ongoing melanoma care. This randomized controlled trial examined the efficacy of a psychoeducational intervention to reduce FCR and improve psychologic adjustment in this patient group compared with usual care. 
 
The intervention comprised a newly developed psychoeducational resource and three telephone-based psychotherapeutic sessions over a 1-month period timed in accordance with dermatologic appointments. Participants were randomly assigned to intervention (n = 80) or usual care (n = 84). Assessments were completed at baseline, 1 month, and 6 months after dermatologic appointments. Linear mixed models were used to examine differences between treatment and control groups for patient-reported outcomes, including FCR, anxiety, stress, depression, melanoma-related knowledge, health behaviors, satisfaction with melanoma care, unmet needs, and health-related quality of life. 
 
At 6 months, the intervention group reported lower FCR severity, trigger, and distress scores than the control group in the baseline-adjusted models; the between-group mean difference was -1.9 for FCR severity, -2.0 for FCR triggers, and -0.7 for FCR distress. The decrease in FCR severity (but not triggers or distress) remained statistically significant after adjustment for other covariates. At 6 months, the intervention group also reported lower stress and improved melanoma-related knowledge compared with the control group. No differences were found between groups for other secondary outcomes.
 
This newly developed evidence-based psychoeducational intervention was effective in reducing FCR and stress and increasing melanoma-related knowledge in people at high risk for another melanoma.

If you as the patient or as a family member are having trouble dealing with the psychological burden of melanoma and its treatments...seek help.  Your doc may not offer it, but you can certainly ask for it!!!  And sometimes....it really helps to just - phone a friend!!! - c

Perception....patient vs doctors in cancer care

I touched on this report when it came out of the Boston meeting here:  Patients vs Docs - Treatment goals for cancer patients

Patient Versus Physician Valuation of Durable Survival Gains: Implications for Value Framework Assessments. Shafrin, Schwartz, Okoro, Romley. Value Health. 2017 Feb;20.

Previous research indicates that patients value therapies that provide durable or tail-of-the-curve survival gains, but it is unclear whether physicians share these preferences.
To compare patient and physician preferences for treatments with a positive probability of durable survival gains relative to those with fixed survival gains.

Patients with advanced stage melanoma or lung cancer and the oncologists who treated these patients were surveyed. The primary end point was the share of respondents who selected a therapy with a variable survival profile, with some patients experiencing long-term durable survival and others experiencing much shorter survival, compared to a therapy with a fixed survival duration. Parameter estimation by sequential testing was applied to calculate the length of nonvarying survival that would make respondents indifferent between that survival and therapy with durable survival.

The sample comprised 165 patients (lung = 84, melanoma = 81) and 98 physicians. For lung cancer, 65.5% of patients preferred the therapy with a variable survival profile, compared with 40.8% of physicians. For melanoma, these figures were 63.0% for patients and 29.7% for physicians . Patients' indifference point implied that therapies with a variable survival profile are preferred unless the treatment with fixed survival had 13.6 months (melanoma) or 11.6 months (lung) longer mean survival; physicians would prescribe treatments with a fixed survival if the treatment had 7.5 months (melanoma) or 1.0 month (lung) shorter survival than the variable survival profile. 

Patients place a high value on therapies that provide a chance of durable or "tail-of-the-curve" survival, whereas physicians do not. Value frameworks should incorporate measures of tail-of-the-curve survival gains into their methodologies.

Just putting it out there one more one!!  A patient's perspective should be INCLUDED (at the very least) in their own health care decisions AND in research/trial development and implementation!!!  Cause, yeah!  We ratties...as noted in the middle of this post:  Nivolumab Shows Impressive OS in melanoma...be riding the tail!!!

Hang tough and fight for the treatment YOU think best for YOU!!! - c

Sew Chaotically! - Fit and flare top - B5890

I've had this pattern for a while and finally stitched one up for Roo as part of her spring wardrobe update!!!  Spring Tops!!!

Here, I used a light weight seersucker from either JoAnn's or Hancock (back in the day!!) and the collarless version of D (ever so slightly shorter due to limited yardage).

It sewed up beautifully!!!  The tucks (pleats?) are interestingly made and super easy!  My only change was to make the neckline a little lower in the front.  (Left per the pattern indications it would have been high, y'all!)

Rosie's went together so easily and was so cute I made myself one!!!

This one is a sleeveless view A, again with the lowered neckline.  I am proud of the pattern placement!  A challenge only because of limited yardage, but still.  I love how this one looks, but because it is made of quilting cotton (purchased before I knew the difference) it does require ironing, which is a bit of a pain.

On the flip side, making my own binding from the fabric was easy peasy since it took to the iron very well!  Previously, this was something I thought I'd never do.  But I rather liked making it and using it has been a treat!!

The third is the charm!!  This one is full length view D (without collar and with the slight neckline modification) in a seersucker that was a little heavier than the one for Roo.  Gotta say, seersucker works very well for this pattern as it holds the drape without being stiff and no ironing is required!

I added a little button with loop to the top of this one.

And while it needs to get a little warmer to enjoy wearing it at home, it was super fun to wear during our little "spring break"!  Travel Chaotically! - The Gulf Coast - Spring Break and Me Mades, Baby!!!

This is a fun little top that fits very well!!  Maybe I should make it into a dress!!!!  Sew Chaotically! - les

Everything Cures Melanoma: Installment #6

Here we go again!  If all these things cure melanoma....why do we have it???  Don't get me wrong...if any of these readily available (hmmmm.... Cough! Cough!) items hold the key to a cure....I am ALL FOR IT!!!  Here's a prior compilation:  Everything Cures Melanoma - Redux #5

Identification of predominant phytochemical compounds and cytotoxic activity of wild olive leaves (Olea europaea L. ssp. sylvestris) harvested in south Portugal. Makowska-Wąs, Galanty, Gdula-Argasińska, et al. Chem Biodivers. 2016 Dec 16.

This study has been aimed at providing a qualitative and quantitative evaluation of selected phytochemicals such as phenolic acids, flavonoids, oleuropein, fatty acids profile, and volatile oil compounds, present in wild olive leaves harvested in Portugal, as well as at determining their antioxidant and cytotoxic potential against human melanoma HTB-140 and WM793, prostate cancer DU-145 and PC-3, hepatocellular carcinoma Hep G2 cell lines, as well as normal human skin fibroblasts BJ and prostate epithelial cells PNT2. Gallic, protocatechuic, 4-hydroxybenzoic, vanillic acids, apigenin 7-O-glucoside, luteolin 7-O-glucoside, and rutin were identified in olive leaves. The amount of oleuropein was equal to 22.64 g/kg dry weight. (E)-anethole (32.85%), fenchone (11.89%), and (Z)-3-nonen-1-ol (8%) were found to be the main constituents of the oil volatile fraction, whereas palmitic, oleic, and alpha-linolenic acid were determined to be dominating fatty acids. Olive leaves methanol extract was observed to exerted a significant, selective cytotoxic effect on Du-145 and PC-3 cell lines. Except the essential oil composition, evaluated wild olive leaves, with regard to their quantitative and qualitative composition, do not substantially differ from the leaves of other cultivars grown for industrial purposes and they reveal considerable antioxidant and cytotoxic properties. Thus, the wild species may prove to be suitable for use in traditional medicine as cancer chemoprevention.

Data on melanin production in B16F1 melanoma cells in the presence of emu oil. Ito, Minami, Sagane, et al. Data Brief. 2016 Nov 17.

Here, we present data on the effects of emu oil, obtained from emu (Dromaius novaehollandiae) fat deposits, on melanogenesis in B16F1 murine melanoma cells. The cells were cultured in media containing different concentrations of emu oil, and the melanin content of these cells was measured using a microplate reader. Next, melanin content was measured for cells cultured with α-melanocyte-stimulating hormone. This article reports the different melanin contents as μg melanin/mg cellular protein, by using bar graphs with error bars. The present data imply that emu oil reduces the cellular melanin production.

Augmentation of Cytolytic Activity in Murine Natural Killer Cells and Inhibition of Tumor Growth by the Ethanol Fraction of Oyster Extract. Sakaguchi, Zhong, Kawai, et al. Integr Cancer Ther. 2016 Dec 5.

A reduced number and/or reduced activity of natural killer (NK) cells, which are important for defense against a variety of cancers and viral infections, occur under various stress conditions and in patients with various diseases. In this article, we report that the 30% to 50% ethanol precipitate of oyster extract (EPOE50) dose-dependently enhanced the activity of mouse spleen NK cells in vitro and in vivo. The activity of EPOE50 was eluted with a molecular weight of about 2000 by gel filtration and was inactivated by periodate but not by proteinase K. The activity of highly purified NK cells was also augmented by EPOE50 but not by oligodeoxyribonucleotide 1585, which mimics bacterial DNA. Administration of EPOE50 to mice stimulated splenic NK cell activity without a change in splenic NK cell populations. Although the proliferation of B16 tumor cells in vitro was slightly stimulated by EPOE50, the growth of B16 melanoma in vivo was dose-dependently suppressed by administration of EPOE50. Taken together, our results indicate that EPOE50 augmented NK cell activity and that its administration to mice inhibited tumor growth presumably through the activation of NK cells and also suggest that the active substance is a sugar-containing oligomer or polymer and is not of bacterial origin.

Lectin from seeds of a Brazilian lima bean variety (Phaseolus lunatus L. var. cascavel) presents antioxidant, antitumour and gastroprotective activities. E Lacerda, do Nascimento, de Lacerda, et al. Int J Biol Macromol. 2016 Oct 28.

Lectins are proteins able to interact specifically and reversibly with carbohydrates. They are present in all living beings, particularly in legume seeds, which have many biological functions. The aim of this study was to isolate, characterize and verify antioxidant, anti-hemolytic, antitumor and gastroprotective activities in a lectin present in seeds of Phaseolus lunatus L. var. cascavel (PLUN). The isolation of lectin was performed by size exclusion chromatography on Sephadex G-100, which was isolated from a protein capable of agglutinating only human erythrocytes type A, being this the only inhibited haemagglutination n-acetyl-d-galactosamine. Its weight was estimated by PAGE is 128kDa. The lectin is thermostable up to 80°C and is active between pH 2 to 11. As 8M urea was able to denature the lectin. PLUN is a glycoprotein consisting of 2% carbohydrate and has antioxidant action with ascorbic acid equivalent antioxidant capacity (μMAA/g) of 418.20, 326 and 82.9 for total antioxidant activity, ABTS radical capture and capture of DPPH radical, respectively. The lectin has antitumor activity against melanoma derived cells at doses of 100 and 50mg/ml, reducing up to 83% tumor cells, and gastroprotective action, reducing up to 63% damaged area of ​​the stomach induced by ethanol.

Potential anticancer activity of lichen secondary metabolite physodic acid. Cardile, Graziano, Avola, et al. Chem Biol Interact. 2016 Dec 21.

Secondary metabolites present in lichens, which comprise aliphatic, cycloaliphatic, aromatic and terpenic compounds, are unique with respect to those of higher plants and show interesting biological and pharmacological activities. However, only a few of these compounds, have been assessed for their effectiveness against various in vitro cancer models. In the present study, we investigated the cytotoxicity of three lichen secondary metabolites (atranorin, gyrophoric acid and physodic acid) on A375 melanoma cancer cell line. The tested compounds arise from different lichen species collected in different areas of Continental and Antarctic Chile. The obtained results confirm the major efficiency of depsidones. In fact, depsides atranorin and gyrophoric acid, showed a lower activity inhibiting the melanoma cancer cells only at more high concentrations. Whereas the depsidone physodic acid, showed a dose-response relationship in the range of 6.25-50 μM concentrations in A375 cells, activating an apoptotic process, that probably involves the reduction of Hsp70 expression. Although the molecular mechanism, by which apoptosis is induced by physodic acid remains unclear, and of course further studies are needed, the results here reported confirm the promising biological properties of depsidone compounds, and may offer a further impulse to the development of analogues with more powerful efficiency against melanoma cells.

Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition. Caini, Masala, Sajeva, et al. Int J Cancer. 2017 Feb 20.

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma, however epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multi-centre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. ... Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men, but not among women. There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

Wild olive leaves, emu oil, oyster goo, Brazilian lima beans with a cup of coffee anyone (or for you dudes, at least!)???  I'm pass'n my plate!!! 

For what it's worth! - c

Digoxin and trametinib for BRAF wild type melanoma

With some relation to my Tuesday post....the use of older meds normally indicated for other diseases/conditions now being re-purposed for use in melanoma where I talked about mebendazole and imiquimod, here we look at the use of Digoxin.  Dig, also called Lanoxin, is a cardiac glycoside that makes the heart beat more regularly and stronger.  It is used to treat heart failure and arrhythmias. Given its cardiogenic effects, it is no small thing to use it in other ways and it does have its own set of possible side effects as does any other medication.  I posted this abstract regarding digoxin and trametinib out of ASCO last year:  See the first article -Digoxin plus trametinib therapy of BRAF wild type metastatic melanoma patients

Now there is this update:

Digoxin Plus Trametinib Therapy Achieves Disease Control in BRAF Wild-Type Metastatic Melanoma Patients. Frankel, Eskoocak, Gill, et al. Neoplasia. 2017 Mar 6.

This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0.25 mg and trametinib 2 mg given orally once daily in 20 patients with advanced, refractory, BRAF wild-type melanomas. The most common adverse events were rash, diarrhea, nausea, and fatigue. The response rate was 4/20 or 20% with response durations of 2, 4, 6, and 8 months. The disease control rate (including partial responses and stable disease) was 13/20 or 65% of patients, including 5/6 or 83% of patients with NRAS mutant melanomas and 8/14 or 57% of NRAS wild-type melanomas. Patients with stable disease had disease control for 2, 2, 2, 4, 5, 6, 7, 10, and 10 months. Xenografts from four patients recapitulated the treatment responses observed in patients. Based on these pilot results, an expansion arm of digoxin plus MEK inhibitor is warranted for NRAS mutant metastatic melanoma patients who are refractory or intolerant of immunotherapy.

Digoxin plus trametinib is well tolerated and achieves a high rate of disease control in BRAF wild-type metastatic melanoma patients.

For what it's worth.  - c

Imiquimod and Mebendazole...drugs repurposed for mousie melanoma

Folks in melanoma world tend to go nuts when reports like these hit the news stand.  Partly out of desperation for an effective treatment, but also because sometimes such reports fail to make it clear that these great strides were attained in mousies rather than ratties.  Despite the skepticism my first sentence may convey, mice ARE the first step toward ratties and if they can find a treatment that works for more of my melanoma peeps, I'll take it!!!

First up is imiquimod, a cream that is usually used topically to treat venereal warts, basal cell carcinoma, and actinic keratosis.  These little mice seem to have had it applied topically (??? I think) as well as having it injected in their tail veins (not sure which vein that would be in ratties!!!) followed by radiation and it seemed to make melanoma lesions more responsive to that treatment.

Next there's mebendazole, an old, cheap, oral drug most often used to treat pin worms in kids...but also infestations of many other wormy critters as well as giardia.  Generally, it is safe to use, though in large doses can cause bone marrow suppression.  As an aside, I had a good many doses of this as a child because my mother seemed to have been of the persuasion that an ounce of prevention was worth a pound of cure....not that this med works like that for worms nor melanoma, as I sit here today as a Stage IV melanoma rattie!!!

At any rate, here you go.....

The TLR7 agonist imiquimod induces anti-cancer effects via autophagic cell death and enhances anti-tumoral and systemic immunity during radiotherapy for melanoma. Cho, Lee, Ko, et al. Oncotarget. 2017 Feb 15.

Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines. The results also confirmed that the autophagy process was accelerated via the reactive oxygen species (ROS)-mediated MAPK and NF-κB signaling pathway in the cells pretreated with IMQ combined with IR. Mice subcutaneously injected with melanoma cells showed a reduced tumor growth rate after treatment with IMQ and IR. Treatment with 3-methyladenine (3-MA), ameliorated the anti-cancer effect of IMQ combined with IR. Additionally, the combination therapy enhanced anti-cancer immunity, as demonstrated by an increased number of CD8+ T cells and decreased numbers of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs) in the tumor lesions. Moreover, the combination therapy decreased the number of metastatic nodules in the lungs of mice that were injected with B16F10 cells via the tail vein. In addition, the combination therapy enhanced systemic anti-cancer immunity by increasing the abundances of T cell populations expressing IFN-γ and TNF-α. Therefore, these findings suggest that IMQ could serve as a radiosensitizer and immune booster during radiotherapy for melanoma patients.

The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.  Simulam-Rosenthal, Dakshanamurthy, Gaur, et al. Oncotarget. 2017 Feb 2.

Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation. Reverse Phase Protein Array (RPPA) and immunoblot analyses show that both trametinib and MBZ inhibit the MAPK pathway, and cluster analysis revealed a protein cluster showing strong MBZ+trametinib - inhibited phosphorylation of MEK and ERK within 10 minutes, and its direct and indirect downstream targets related to stress response and translation, including ElK1 and RSKs within 30 minutes. Downstream ERK targets for cell cycle, including cMYC, were down-regulated, consistent with S- phase suppression by MBZ+trametinib, while apoptosis markers, including cleaved caspase-3, cleaved PARP and a sub-G1 population, were all increased with time. These data suggest that MBZ, a well-tolerated off-patent approved drug, should be considered as a therapeutic option in combination with trametinib, for patients with NRASQ61mut or other non-V600E BRAF mutant melanomas.  

Thanks to all the dear mousies!! love, rattie

Travel Chaotically! - The Gulf Coast - Spring Break and Me Mades, Baby!!!

A spur of the moment spring break!  With my B!!!!

A beautiful (and delicious) dinner at One Fish, Two Fish in Pensacola.  Wearing my me-made  Marled grey easy sweater - M6844

Pensacola beach really is as beautiful as any playa on earth.

With the cutest beach bum....

....and his alien friend!!!

'Sew' many Sorbetto's, 'sew' little time.  4 of Colette's Sorbetto's so far!  You can literally wear them anywhere!!!

There was a little rain as we made our way to Gulf Shores. But after a yummy dinner at Bahama Bob's we were given a beautiful rainbow!

A lovely walk through Bon Secour National Wildlife Refuge...

Hair in the air and just don't care!!! But, I LOOOOVE this fit and flare top....B5890.  This is actually my third make!  To be blogged about soon!

I was lucky to have such a lovely, relaxing treat.  And yes!  You can have melanoma and vitiligo and a wonderful time at the beach.  There were hats and long sleeves and sun screen for hikes.  Walks on the beach are perfect first thing in the morning and in the evening.  All with my sweet bestie!!! Thanks, Bentie.  It is spring again, Baby!!!  love, les