Vitamin D3

Please note my Vit D3 intake is monitored by two different doctors (allopath; naturopath) this is the only issue they both agree on. My levels are monitored every three months by blood tests. If I miss a dose or two a week, I don't sweat it. I do not spend time in the sun due to rads. I know my body and value blood tests for accuracy, I'm a numbers person, so this works for me. My dx, two different types of bc in the same tumor.

NOTE: take a 25-hydroxyvitamin D blood test to baseline and every 3 months thereafter to assess and adjust your dosage so your optimal blood levels will be where they should be year-round.

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Check back for updates on this post. . .

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http://www.ncbi.nlm.nih.gov/pubmed/27120467

See comment in PubMed Commons belowBreast Cancer Res Treat. 2016 Apr 27. [Epub ahead of print]

Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer.

Thakkar A^1,2, Wang B¹, Picon-Ruiz M¹, Buchwald P³, Ince TA^4,5.

Author information

• ¹Sylvester Comprehensive Cancer Center, Department of Pathology, Braman Family Breast Cancer Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.
• ²Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami, Miami, FL, USA.
• ³Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL, USA.
• ⁴Sylvester Comprehensive Cancer Center, Department of Pathology, Braman Family Breast Cancer Institute and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA. Tince@miami.edu.
• ⁵, Biomedical Research Building, Room 926, 1501 NW 10th Avenue, Miami, FL, 33136, USA. Tince@miami.edu.

Abstract

Anti-estrogen and anti-HER2 treatments have been among the first and most successful examples of targeted therapy for breast cancer (BC). However, the treatment of triple-negative BC (TNBC) that lack estrogen receptor expression or HER2 amplification remains a major challenge. We previously discovered that approximately two-thirds of TNBCs express vitamin D receptor (VDR) and/or androgen receptor (AR) and hypothesized that TNBCs co-expressing AR and VDR (HR2-av TNBC) could be treated by targeting both of these hormone receptors. To evaluate the feasibility of VDR/AR-targeted therapy in TNBC, we characterized 15 different BC lines and identified 2 HR2-av TNBC lines and examined the changes in their phenotype, viability, and proliferation after VDR and AR-targeted treatment. Treatment of BC cell lines with VDR or AR agonists inhibited cell viability in a receptor-dependent manner, and their combination appeared to inhibit cell viability additively. Moreover, cell viability was further decreased when AR/VDR agonist hormones were combined with chemotherapeutic drugs. The mechanisms of inhibition by AR/VDR agonist hormones included cell cycle arrest and apoptosis in TNBC cell lines. In addition, AR/VDR agonist hormones induced differentiation and inhibited cancer stem cells (CSCs) measured by reduction in tumorsphere formation efficiency, high aldehyde dehydrogenase activity, and CSC markers. Surprisingly, we found that AR antagonists inhibited proliferation of most BC cell lines in an AR-independent manner, raising questions regarding their mechanism of action. In summary, AR/VDR-targeted agonist hormone therapy can inhibit HR2-av TNBC through multiple mechanisms in a receptor-dependent manner and can be combined with chemotherapy.

http://www.ncbi.nlm.nih.gov/pubmed/24239860

Modeling vitamin D actions in triple negative/basal-like breast cancer.

LaPorta E¹, Welsh J².

Author information

• ¹Cancer Research Center, University at Albany, USA; Department of Biomedical Sciences, University at Albany, USA.
• ²Cancer Research Center, University at Albany, USA; Department of Environmental Health Sciences, University at Albany, USA. Electronic address: jwelsh@albany.edu.

Abstract

Breast cancer is a heterogeneous disease with six molecularly defined subtypes, the most aggressive of which are triple negative breast cancers that lack expression of estrogen receptor (ER) and progesterone receptor (PR) and do not exhibit amplification of the growth factor receptor HER2. Triple negative breast cancers often exhibit basal-like gene signatures and are enriched for CD44+ cancer stem cells. In this report we have characterized the molecular actions of the VDR in a model of triple negative breast cancer. Estrogen independent, invasive mammary tumor cell lines established from wild-type (WT) and VDR knockout (VDRKO) mice were used to demonstrate that VDR is necessary for 1,25-dihydroxyvitamin D3 (1,25D) mediated anti-cancer actions in vitro and to identify novel targets of this receptor. Western blotting confirmed differential VDR expression and demonstrated the lack of ER, PR and Her2 in these cell lines. Re-introduction of human VDR (hVDR) into VDRKO cells restored the anti-proliferative actions of 1,25D. Genomic profiling demonstrated that 1,25D failed to alter gene expression in KO240 cells whereas major changes were observed in WT145 cells and in KO clones stably expressing hVDR (KO(hVDR) cells). With a 2-fold cutoff, 117 transcripts in WT145 cells and 197 transcripts in the KO(hVDR) clones were significantly altered by 1,25D. Thirty-five genes were found to be commonly regulated by 1,25D in all VDR-positive cell lines. Of these, we identified a cohort of four genes (Plau, Hbegf, Postn, Has2) that are known to drive breast cancer invasion and metastasis whose expression was markedly down regulated by 1,25D. These data support a model whereby 1,25D coordinately suppresses multiple proteins that are required for survival of triple-negative/basal-like breast cancer cells. Since studies have demonstrated a high prevalence of vitamin D deficiency in women with basal-like breast cancer, correction of vitamin D deficiency in these women represents a reasonable, but as yet untested, strategy to delay recurrence and extend survival. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

KEYWORDS:

Breast cancer; Invasion; Microarrays; Vitamin D

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From NIH site

Vitamin D

Cancer
Laboratory and animal evidence as well as epidemiologic data suggest that vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Read more from link below.

https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

3D Mammograms

Billing info; AMA; Not covered on insurance yet

CA locations

http://www.checksutterfirst.org/imaging/services/b...

https://www.lassenmedical.com/services/3d-mammogra...

http://www.hoag.org/Specialty/Breast-Program/Pages...

https://www.elcaminohospital.org/

http://www.nsradiology.com/locations/north-state-i...

https://www.pvhmc.org/#About_3D_Mammography

http://mdimaging.net/services/3D-mammography.php

3D mammo completed in June 2015; I was one of the first to use the new equipment; I have Aetna; billing code 77062/radiology = 3DMammo; is not a covered expense because it's considered experimental by my insurance company. I am appealing the decision and requesting the hospital oncology department address this issue and provide supporting evidence, as this has now replaced the 2D equipment. Someone forgot to update their billing data to cover said oncology machine upgrades for hundreds of hospitals across the US. Unless we (the cancer patients) say something, the patient will get billed when the performing facility should have the billing changes coordinated with the insurance companies on what is current and accurate with new equipment, not experimental equipment.

Billed amount: $590

Ineligible amount: $155

Approved amount: $235

Not covered amount: $200 (appealing this charge)

https://www.supercoder.com/my-ask-an-expert/topic/...

User id : 23481 Posted 9 months ago

Our facility performs digital mammograms - are these new codes used to report digital mammograms?

SuperCoder Posted 9 months ago

You will continue to bill the same way for digital mammogram as you were doing.

These new codes are introduced to include the practice expense of breast tomosynthesis when done with digital mammogram. Breast tomosynthesis is a new technology.

Digital mammography with breast tomosynthesis involves "two separate data acquisitions with two different sets of images, requiring the accompanying increased physician work and training," the association explained. "Digital mammography alone requires a single data acquisition per view, producing one image set involving less physician work and training to interpret."

Until now, no separate CPT codes existed for breast tomosynthesis, and providers assigned unlisted diagnostic radiographic procedure code 76499. These new codes 77061, 77062, and 77063 are introduced to address diagnostic and screening breast tomosynthesis.

Keyword Search: Financial Assistance w/ meds, breast cancer

Pfizer RxPathways: Connecting Patients to the Help They Need

http://www.pfizerrxpathways.com

For more than 25 years, Pfizer has offered a number of assistance programs to help eligible patients access their prescription medicines. To answer patients' changing needs and make services more accessible, they have combined existing programs into one program called Pfizer RxPathways.

Pfizer RxPathways is a comprehensive assistance program that provides eligible patients with a range of support services, including insurance counseling, co-pay assistance,* and access to medicines for free or at a savings.

NOTE: If you have specific questions regarding Pfizer financial assistance (insurance coverage, coupons, discounts, c0-pays, etc.), please contact Pfizer directly to discuss programs, terms and qualifications available to you.

Vaginal Estrogen Therapy for Patients with Breast Cancer

Vaginale Östrogentherapie bei Patientinnen mit Mammakarzinom

Geburtshilfe Frauenheilkd. 2013 Oct; 73(10): 1017–1022.

doi: 10.1055/s-0033-1350876

M. Moegele,S. Buchholz,S. Seitz,C. Lattrich, and O. OrtmannUniversity Medical Center Regensburg, Department of Gynecology and Obstetrics, Regensburg

Correspondence Dr. Maximilian Moegele University Medical Center Regensburg, Gynecology and Obstetrics, Landshuterstreet 65, 93053 Regensburg, ; Email: ed.fesojtssatirac@elegeomm

Author information ► Article notes ► Copyright and License information ►

To read the full article, please select the link below:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862044/

Abstract

On account of the good prognosis for patients with breast cancer, improving or maintaining the quality of life in the aftercare period is becoming more and more important. In particular, the increasing usage of aromatase inhibitors in the past few years has led to an increased incidence of vaginal atrophy with symptoms such as vaginal dryness, petechial bleeding, dyspareunia and recurrent cystitis. And just these symptoms have a detrimental impact on the quality of life of breast cancer patients. Application of a topical estrogen therapy represents the most effective means to treat vaginal atrophy. The use of a systemic or, respectively, topical hormone therapy is, however, contraindicated for breast cancer patients. Further clinical trials are needed in order to assess the safety of vaginal estrogen therapy.

Key words: breast cancer, vaginal atrophy, hormone therapy, quality of life, pain

Lymphedema

http://lymphaticnetwork.org/

https://medlineplus.gov/lymphedema.html

http://lymphaticnetwork.org/(for the complete study results select this link)

Oncol Nurs Forum. Author manuscript; available in PMC 2014 Jan 10.

Published in final edited form as:

Oncol Nurs Forum. 2013 Jul; 40(4): 10.1188/13.ONF.383-393.

doi: 10.1188/13.ONF.383-393

A Pilot Randomized Trial Evaluating Low-Level Laser Therapy as an Alternative Treatment to Manual Lymphatic Drainage for Breast Cancer-Related Lymphedema

Related Lymphedema

Sheila H. Ridner, PhD, RN, FAAN, Ellen Poage-Hooper, MPH, MSN, NP-C, CLT-LANA, Collin Kanar, MD, Jennifer K. Doersam, BS, Stewart M. Bond, PhD, RN, AOCN, and Mary S. Dietrich, PhD

Sheila H. Ridner, Vanderbilt University School of Nursing Nashville, TN;

Contributor Information.

Author information ► Copyright and License information ►

Abstract

Purpose/Objectives

To examine the impact of advanced practice nurse (APN) administered low level laser therapy (LLLT) as both a stand-alone and complementary treatment for arm volume, symptoms, and quality of life (QOL) in women with breast cancer related lymphedema.

Design

A three-group, pilot, randomized clinical trial.

Setting

A private rehabilitation practice with two locations in the southwestern United States.

Sample

46 breast cancer survivors with treatment related lymphedema.

Methods

Patients were screened for eligibility and then randomized to either manual lymphatic drainage (MLD) for 40 minutes, LLLT for 20 minutes, or, 20 minutes of MLD followed by 20 minutes of LLLT. Compression bandaging was applied after each treatment. Data were collected pre-treatment, daily, weekly, and at the end of treatment.

Main Research Variables

Independent variables consisted of three types of APN administered lymphedema treatment. Outcome variables included limb volume, extracellular fluid, psychological and physical symptoms, and QOL.

Findings

No statistically significant between group differences were found in volume reduction; however, all groups had clinically and statistically significant reduction in volume. No group differences were noted in psychological and physical symptoms, or QOL; however, treatment related improvements were noted in symptom burden within all groups. Skin improvement was noted in each group that received LLLT.

Conclusions

LLLT with bandaging may offer a time saving therapeutic option to conventional MLD. Alternatively compression bandaging alone could account for the demonstrated volume reduction.

Implications for Nursing

APNs can effectively treat lymphedema. APNs in private healthcare practices can serve as valuable research collaborators.

Go to:

Introduction

Decreases in breast cancer mortality rates, combined with the relatively high five-year survival rates for local and regional tumors, suggest that the estimated 2.6 million breast cancer survivors living in the United States (American Cancer Society, 2011; Herdman et al., 2005; Siegel, Naishadham, & Jemal, 2013) represent a significant and growing population. Lymphedema swelling in the affected arm is a serious problem for many breast cancer survivors with documented rates of 6 to 40% (Armer, Fu, Wainstock, Zagar, & Jacobs, 2004; Ball, Waters, Fish, & Thomas, 1992; Ivens et al., 1992; Kissin, Querci Della Rovere, Easton, & Westburry, 1986; Petrek & Heelan, 1998; Wilke et al., 2006). This range includes the 7%-22% of women with lymphedema following sentinel node biopsies (Armer et al., 2004; Wilke et al., 2006). Lymphedema can occur during treatment, or many years later (Coward, 1999; Ramos, O'Donnell, & Knight, 1999; Stanton, Levick, & Mortimer, 1997). Lymphedema is a progressive disease. Initially, the limb will swell and pit with pressure (stage I). Overtime, the limb may become firmer, not pit with pressure, and skin changes may be noted (stage II). In its most severe form, (stage III), impaired lymph flow causes very thick skin and large skin folds, and invasive treatments may be needed to reduce bulk (Pain & Purushotham, 2000). Many problematic symptoms such as fatigue and altered sensations in the limb can occur with lymphedema (Ridner, 2005) and some breast cancer survivors with lymphedema experience poor quality of life (QOL; Park, Jang, & Seo, 2012; Ridner, 2005). To improve health outcomes in this population, access to effective therapeutic modalities is necessary.

Arm Exercises

Select the link below for illustrations and details on each exercise identified:

https://www.verywell.com/how-to-do-arm-lymphedema-exercises-430210

After lymph node removal, you may experience arm lymphedema. Some extra fluid may build up in your hand or arm, causing them to swell. The idea behind arm exercise and lymphedema is that arm muscle contractions may help move lymph fluid back to veins in your armpit and neck, so it can rejoin your blood circulation. When the lymph fluid goes back into circulation, your swelling should go down.

These simple gentle exercises can help the proteins in lymph fluid to be reabsorbed, and your arm lymphedema symptoms to diminish or disappear. Be sure to discuss your exercise plans with your doctor - before you start.

If you have recently had surgery, wait until your surgical drains and sutures are out, before trying these exercises. Do these exercises gently - you're not body building here - and do not exercise to the point of pain. Always wear your compression sleeve on your affected arm while exercising. Stop exercising if your arm begins to swell or turn red.

Dress in loose, comfortable clothing - style is not important for these exercises. Warm your affected arm and hand before starting to exercise - take a shower, tub soak, or use a warm compress for about 20 minutes. Be regular about doing your arm lymphedema exercises. This will aid your recovery and give you the best results.

Here's what is recommended to get started:

• A set of 1 pound free weights
• Your compression sleeve
• A small flexible ball
• A hard chair to sit on
• An area big enough to lay down on
• Optional: A pair of walking poles: Fitness, Nordic, or Exer-striding poles

Ball Squeeze - Seated Exercise

Arm lymphedema can happen after lymph nodes are removed during breast cancer surgery. Gentle exercise can help reduce swelling caused by lymphedema. Here's how to do the ball squeeze exercise.

You can do the ball squeeze exercise with your surgery-side arm, as well as with your unaffected arm. Use a flexible ball that is a bit larger than your palm. Your exercise ball should not be heavy and should offer some resistance to your grip. The proper ball will spring back into shape when you release it, but will require some pressure to squeeze it. You will feel muscles in your fingers, lower and upper arm working as you do the ball squeeze. This muscle movement should help move excess lymph fluid back into circulation and help you avoid swelling.

Remember: Always wear your compression sleeve on your affected arm during exercise.

1. Sit or stand with good posture - keep your back and neck straight and your shoulders relaxed. Grasp your exercise ball lightly between your palm and fingers. Extend your arm in front of you, holding your arm higher than your heart.
2. While keeping your arm elevated, squeeze the ball with your fingers as tightly as you can. Hold the squeeze for about 3 seconds, then release.

Repeat the ball squeeze exercise 5 to 7 times. If your arm tires quickly, take breaks. You will gradually build up enough strength and stamina to do the ball squeeze several times without resting.

Next Exercise: Elbow Flexion - another seated exercise.

For additional exercises select this link:

https://www.verywell.com/how-to-do-arm-lymphedema-exercises-430210

Decreased copper and zinc in sera of Chinese vitiligo patients: a meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/24517587

Search words: copper; meta-analysis; vitiligo; zinc; clinical study

J Dermatol. 2014 Mar;41(3):245-51. doi: 10.1111/1346-8138.12392. Epub 2014 Feb 12.

Zeng Q¹, Yin J, Fan F, Chen J, Zuo C, Xiang Y, Tan L, Huang J, Xiao R.

Department of Dermatology, Third Xiangya Hospital, Changsha, China

Abstract

Abnormalities of copper (Cu) and zinc (Zn) are involved in the etiology and pathogenesis of vitiligo. However, controversial results exist now on Cu and Zn in serum of vitiligo patients. The purpose of this study is to compare the serum levels of Cu and Zn between vitiligo patients and healthy controls. In the meta-analysis, 16 studies with a total of 891 vitiligo cases and 1682 healthy controls were included. The levels of serum Cu and Zn were compared between groups of case and control. The serum levels of Cu were significantly lower in vitiligo patients than in healthy controls (Z = 4.04, P < 0.0001; standardized mean difference [SMD], -0.9; 95% confidence interval [CI], -1.34 to -0.47). The levels of serum Zn were also significantly lower in vitiligo patients than in healthy controls (Z = 4.88, P < 0.00001; SMD, -1.09; 95% CI, -1.51 to -0.64). These results demonstrate that decreased levels of serum Cu and Zn are generally present in Chinese vitiligo patients. This may offer support for clinical administration of oral Cu and Zn supplements.

© 2014 Japanese Dermatological Association.

PMID: 24517587

DOI: 10.1111/1346-8138.12392

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Serum Levels of Copper and Zinc in Patients with Rheumatoid Arthritis: a Meta-analysis.

Biol Trace Elem Res. 2015 Nov;168(1):1-10. doi: 10.1007/s12011-015-0325-4. Epub 2015 Apr 15.

Xin L¹, Yang X¹, Cai G¹, Fan D¹, Xia Q¹, Liu L¹, Hu Y¹, Ding N¹, Xu S², Wang L¹, Li X¹, Zou Y¹, Pan F³.

Author information

• ¹Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.
• ²Department of Rheumatism and Immunity, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
• ³Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China. famingpan@ahmu.edu.cn.

Abstract

Many publications with conflicting results have evaluated serum levels of copper (Cu) and zinc (Zn) in patients with rheumatoid arthritis (RA). To derive a more precise estimation of the relationship, a meta-analysis was conducted. Relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014. Weighted mean difference (WMD) with a 95 % confidence interval (95 % CI) was calculated using STATA 11.0. A total of 26 studies, including 1444 RA cases and 1241 healthy controls, were collected in this meta-analysis. Pooled analysis found that patients with RA had a higher serum level of Cu and a lower serum Zn level than the healthy controls (Cu (μg/dl), WMD = 31.824, 95 % CI = 20.334, 43.314; Zn (μg/dl), WMD = -12.683, 95 % CI = -19.783, -5.584). Subgroup analysis showed that ethnicity had influence on the serum level of Cu (μg/dl) (Caucasian, WMD = 43.907, 95 % CI = 35.090, 52.723, P < 0.001; Asian, WMD = 14.545, 95 % CI = -12.365, 41.455, P = 0.289) and Zn (μg/dl) (Caucasian, WMD = -11.038, 95 % CI = -23.420, 1.344, P = 0.081; Asian, WMD = -14.179, 95 % CI = -18.963, -9.394, P < 0.001) in RA and healthy controls. No evidence of publication bias was observed. This meta-analysis suggests that increased serum level of Cu and decreased serum level of Zn are generally present in RA patients.

KEYWORDS: Copper; Meta-analysis; Rheumatoid arthritis; Zinc

PMID:25869414

DOI:10.1007/s12011-015-0325-4

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Biol Trace Elem Res. 2015 Oct;167(2):225-35. doi: 10.1007/s12011-015-0304-9. Epub 2015 Mar 29.

The Association Between Serum Levels of Selenium, Copper, and Magnesium with Thyroid Cancer: a Meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/25820485

Shen F¹, Cai WS, Li JL, Feng Z, Cao J, Xu B.

Search words: Serum Levels of Selenium, Copper, and Magnesium; thyroid cancer

Author information

• ¹Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Yuexiu District, Guangzhou, 510180, People's Republic of China.

Abstract

There are conflicting reports on the correlation between serum levels of selenium (Se), copper (Cu), and magnesium (Mg) with thyroid cancer. The purpose of the present study is to clarify the association between Se, Cu, and Mg levels with thyroid cancer using a meta-analysis approach. We searched articles indexed in PubMed published as of January 2015 that met our predefined criteria. Eight eligible articles involving 1291 subjects were identified. Overall, pooled analysis indicated that subjects with thyroid cancer had lower serum levels of Se and Mg, but higher levels of Cu than the healthy controls [Se: standardized mean difference (SMD) = -0.485, 95% confidence interval (95%CI) = (-0.878, -0.092), p = 0.016; Cu: SMD = 2.372, 95%CI = (0.945, 3.799), p = 0.001; Mg: SMD = -0.795, 95%CI = (-1.092, -0.498), p < 0.001]. Further subgroup analysis found lower serum levels of Se in thyroid cancer in Norway [SMD = -0.410, 95%CI = (-0.758, -0.062), p = 0.021] and Austria [SMD = -0.549, 95%CI = (-0.743, -0.355), p < 0.001], but not in Poland (SMD = -0.417, 95%CI = (-1.724, 0.891), p = 0.532]. Further subgroup analysis also found that patients with thyroid cancer had higher serum levels of Cu in China [SMD = 1.571, 95%CI = (1.121, 2.020), p < 0.001] and Turkey [SMD = 0.977, 95%CI = (0.521, 1.432), p < 0.001], but not in Poland [SMD = 3.471, 95%CI = (-0.056, 6.997], p = 0.054]. In conclusion, this meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer. However, the subgroup analysis found that there was significant effect modification of Se, Cu levels by ethnic, like China and Poland. Thus, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between Se, Cu, and Mg with thyroid cancer of different human races or regions.

PMID: 25820485

DOI: 0.1007/s12011-015-0304-9

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Search words: Serum Levels of Selenium, Copper, and Magnesium; thyroid cancer

Biol Trace Elem Res. 2013 Jun;153(1-3):5-10. doi: 10.1007/s12011-013-9682-z. Epub 2013 May 3.

search words: Zinc and copper levels in bladder cancer: a systematic review and meta-analysis.

Mao S¹, Huang S. Selenium, Copper, and Magnesium; thyroid cancer

Author information

• ¹Department of Nephrology, Nanjing Children's Hospital, Affiliated to Nanjing Medical University, 72 Guangzhou road, Nanjing, Jiangsu Province 210008, China.

Abstract

It is well documented that oxidative stress is involved in the pathogenesis of bladder cancer. Zinc (Zn) and copper (Cu) are important components of antioxidants. However, the association between Zn or Cu levels and bladder cancer remains elusive. The present study was designed to investigate the alteration of serum and urinary levels of Zn or Cu in bladder cancer patients compared with controls by performing a systematic review. We searched the PubMed, Embase, and Cochrane databases from January 1990 to March 2013 to identify studies that met our predefined criteria. Six studies were included. Bladder cancer patients demonstrated significantly lower levels of serum Zn (three studies, random effects standard mean deviation (SMD): -1.072, 95 % CI: -1.489 to -0.656, P <0.0001), markedly higher levels of serum Cu (three studies, random effects SMD: 1.069, 95 % CI: 0.302 to 1.836, P = 0.006) and urinary Zn (three studies, random effects SMD: 2.114, 95 % CI: 0.328 to 3.899, P = 0.02) compared with controls. No obvious difference was observed in urinary Cu levels between bladder cancer patients and controls (two studies, random effects SMD: 0.153, 95 % CI: -0.244 to 0.55, P = 0.449). No evidence of publication bias was observed. In conclusion, the disorder of Zn and Cu is closely associated with bladder cancer. Frequent monitoring and early intervention should be recommended.

PMID:23640281

DOI:10.1007/s12011-013-9682-z

Flax and Breast Cancer: A Systematic Review

https://www.ncbi.nlm.nih.gov/pubmed/24013641/

Flower G¹, Fritz H², Balneaves LG³, Verma S⁴, Skidmore B², Fernandes R⁵, Kennedy D⁵, Cooley K⁵, Wong R⁶, Sagar S⁶, Fergusson D⁷, Seely D⁸.

Author information

• ¹Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada Ottawa Integrative Cancer Center, Ottawa, Ontario, Canada.
• ²Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada.
• ³University of British Columbia School of Nursing, Vancouver, British Columbia, Canada CAMEO Program, Vancouver, British Columbia, Canada.
• ⁴Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Ottawa Regional Cancer Centre, Ottawa Hospital, Ontario, Canada.
• ⁵Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada The University of Toronto, Toronto, Ontario, Canada.
• ⁶McMaster University, Hamilton, Ontario, Canada.
• ⁷Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
• ⁸Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada Ottawa Integrative Cancer Center, Ottawa, Ontario, Canada Ottawa Hospital Research Institute, Ottawa, Ontario, Canada dseely@ccnm.edu.

Abstract

BACKGROUND:

Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence.

METHODS:

We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer.

RESULTS:

Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (P< .05) and decreased HER2 expression (P< .05) and cell proliferation (Ki-67 index; NS) among newly diagnosed breast cancer patients when compared with placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot flashes, cell proliferation, atypical cytomorphology, and mammographic density, as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients.

CONCLUSIONS:

Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer.

© The Author(s) 2013.

KEYWORDS:

Linum usitatissimum; breast cancer; breast neoplasm; complementary and alternative medicine (CAM); flax; hot flashes; integrative oncology; menopause; phytoestrogen; systematic review

National Women's Health Week

https://www.womenshealth.gov/nwhw/

https://www.womenshealth.gov/a-z-topics/

https://go4life.nia.nih.gov/

Vitamin K2

International Health and Science Foundation
Lindego 7C, 30-148 Krakow, Poland
E-mail: office@ishf.org
www.ishf.org

International Health and Science Foundation

Inspired by passionate people who share a desire to explore new developments in the fields of health and science, the International Health and Science Foundation (ISHF) was founded in 2009. A scientific community independent of business commitments, our activities are based on four main pillars – Innovation, Knowledge, Responsibility, and Cooperation – and are intended to foster a healthy point of view that benefits society. The Foundation's international character allows us to share experiences with other countries, resulting in innovative designs that allows for the implementation of common, useful social and economic goals.

http://www.1mhealthtips.com/vitamin-k2-the-important-nutrient-for-bone-heart-health/

http://vitamink2.org/benefits/introduction/

Cancer

In recent years, various reports have shown that vitamin K2 has anti-oncogenic effects in various cancer cell lines, including leukemia, lung cancer, ovarian cancer, and hepatocellular cancer. Although the exact mechanisms by which vitamin K2 exert its antitumor effect are still unclear, processes, such as cell cycle arrest and apoptosis, appear to contribute to the therapeutic effects of vitamin K2.

In view of vitamin K2's potential to reduce osteoporosis and atherosclerosis risk, and given the fact that these two pathologies are frequently associated with prostate cancer patients undergoing hormonal therapy, development of vitamin K2 as a treatment strategy for prostate cancer could have far-reaching impacts on prostate cancer patients.

Previously, Nimptsch et al. showed an inverse relationship between dietary intake of vitamin K2 and risk of prostate cancer. Interestingly, serum undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K status, is inversely associated with vitamin K2 intake and the development of advanced prostate cancer. Thus, these studies suggest that the intake of vitamin K2 may be beneficial in preventing the progression of prostate cancer. Moreover, vitamin K2 is also shown to enhance the chemotherapeutic efficacy of conventional anticancer drug Sorafenib in the most common type of liver cancer, hepatocellular carcinoma.

6 Things to Know About Using Medicinal Marijuana

National Cancer Institute

https://breastcancer-news.com/2017/06/19/6-things-to-know-about-using-medicinal-marijuana/

Using cannabis or marijuana for medicinal purposes is a hot topic right now among patients and health practitioners. It's regularly touted as a pain reliever for many chronic illnesses, including cancer.

According to the National Cancer Institute, here are some of the facts about medical marijuana and its suggested uses:

It's grown all over the world.
The plant is grown in various places around the world but originated in central Asia. The resin of the plant contains compounds called cannabinoids which are active chemicals that affect the brain and central nervous system.

The key is cannabinoids.
Two of the active cannabinoids that are useful in medical marijuana are delta-9-THC and cannabidiol. Delta-9-THC is psychoactive and is the property that gives users the "high," whereas cannabidiol can help the central nervous system and immune system by decreasing inflammation without any high for the user. Cannabinoids can be taken in several ways: inhaled, sprayed under the tongue, ingested or smoked.

It's been used for thousands of years.
Cannabis has been used for medicinal purposes in some civilizations for thousands of years, but it's only been since the late 19th century that western medicine has started to see the potential for cannabis to be used as a pain reliever.

MORE: How prevalent is cancer?

Medical marijuana is legal in some states.
Recreational use of cannabis is illegal in the United States, but many states now allow the use of medicinal marijuana for patients who are registered.

Cannabinoids can help with the side effects of chemotherapy.
It's thought that cannabinoid drugs may offer pain relief for cancer patients and help with some of the side effects of treatment, including chemotherapy. Though as of right now, there's no hard evidence to support the use of ingesting or smoking cannabis to treat nausea and sickness from chemotherapy.

Cannabis has killed cancer cells in laboratory tests.
There has been clinical research which shows that cannabis has been able to kill cancer cells in laboratory tests, but cannabis has not been approved by the FDA as a treatment for cancer.

Quality-adjusted life year

Tags: Quality and Value in Cancer Care

https://en.wikipedia.org/wiki/Quality-adjusted_life_year

The quality-adjusted life year or quality-adjusted life-year (QALY) is a generic measure of disease burden, including both the quality and the quantity of life lived.^[1][2] It is used in economic evaluation to assess the value for money of medical interventions.^[1] One QALY equates to one year in perfect health.^[2] If an individual's health is below this maximum, QALYs are accrued at a rate of less than 1 per year. To be dead is associated with 0 QALYs.^[3] QALYs can be used to personal decisions, to evaluate programs, and to set priorities for future programs.^[3]

More simply put - QALY is one way in which value is measured in health care. QALY was developed to measure the value of treatments by estimating how long a treatment will extend life. This value is then adjusted to reflect how the treatment will affect quality of life. Therefore, QALY takes into account both quality and quantity of life. A number can then be assigned to a treatment that reflects its QALY value.

Personalized Skin Protection:The Impact of Skin Pigmentation on Melanoma Formation

http://www.skincancer.org/publications/the-melanoma-letter/fall-2015-vol-33-no-2/skin-pigmentation

Breast Cancer Research; tag Melanoma

Elisabeth M. Roider, MD

David E. Fisher, MD, PhD

Department of Dermatology
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA

Melanoma is the fifth most common cancer in the US. Although it accounts for less than two percent of all skin cancer cases, it causes a large majority of skin cancer deaths. Due to socioeconomic changes within the last century, exposing skin to sunlight, often unprotected, has become socially well-accepted; many light-skinned peoples, who are at higher risk of sustaining ultraviolet damage leading to melanoma, tan for cosmetic and recreational reasons. The first sunscreen ingredients were developed in the early 1930s, yet lifetime risk of developing melanoma has steadily increased since then, resulting in an almost 30-fold increase in lifetime melanoma risk (Figure 1).^1,2

Figure 1. Melanoma lifetime risk over the last century seen in a socio-economical context. With greater income and travel, and despite increased knowledge and awareness of ultraviolet damage, risk has increased from approximately 1 in 1500 people in the 1930s to 1 in 50 people today.
(Adapted from D'Orazio, et al, 2013¹ and Jansen, et al, 2013²)

It is well known that the risk of developing cutaneous melanoma varies between ethnicities. As shown by the Center for Disease Control and Prevention (CDC) in 2011, melanoma incidence in the US is about 3-5 times higher in Caucasians than in American Indians and Asians/Pacific Islanders, and about 15-25 times higher than in Hispanics and African Americans. Overall, the annual incidence rate of melanoma is 1 per 100,000 in blacks, 4 per 100,000 in Hispanics, and 25 per 100,000 in non-Hispanic whites.³

Pheomelanin vs. Eumelanin

Clearly, melanin levels play a major part in skin cancer risk. Skin and hair color are determined by the relative amounts of pheomelanin and eumelanin in human hair follicles and epidermis. Pheomelanin, a yellow-to-red pigment, differs from black-to-brown eumelanin in its synthesis pathway, involving L-cysteine and its final oligomer structure, which incorporates benzothiazine and benzothiazole units,instead of the DHI (5,6-dihydroxyindole) and DHICA (5,6-dihydroxyindole-2-carboxylic acid) involved in eumelanin synthesis.⁴

Red hair has been associated with polymorphisms in the melanocortin 1 receptor (MC1R), a seven transmembrane G-protein coupled receptor expressed in the melanocytes of the skin and hair follicles. MC1R variant alleles are associated with red pheomelanin-rich hair in humans.⁵ Pigment formation primarily depends on the activity of different MC1R downstream proteins and the cellular availability of cysteine (Figure 2).^6.7

Figure 2. Pigment synthesis pathway and involved genes in melanocytes.

Pigment synthesis is stimulated by binding of alpha-melanocyte-stimulating hormone (α-MSH) to MC1R on melanocytes. MC1R activates cyclic adenosine monophosphate (cAMP) production, which in turn activates cAMP response element-binding protein (CREB)-mediated transcriptional activation of the microphthalmia-associated transcription factor (MITF). The melanocytic master transcriptional regulator MITF controls transcription of the pigmentation genes tyrosinase and tyrosinase-related proteins 1 and 2 (TYRP1 and TYRP2), which mediate pigment synthesis and the eu- to pheomelanin ratio.^6.7

alpha-melanocyte-stimulating hormone: α-MSH

Agouti signaling protein: ASIP

Melanocortin 1 receptor: MC1R

G-proteins: GP

Adenylate cyclase: AC

cAMP response element-binding protein: CREB

Tyrosinase: TYR

Tyrosinase-related protein 1: TYRP1

Tyrosinase-related protein 2: TYRP2

As 80 percent of all individuals with red hair and pale skin carry loss-of-function polymorphisms in both MC1R alleles, the activity of MC1R's downstream regulated genes in these people is low, resulting in the characteristic orange-red pheomelanin synthesis. This lower-functioning melanin is less effective than eumelanin in shielding against ultraviolet (UV) light, instead exhibiting photosensitizer chemistry that generates reactive oxygen species and DNA damage.⁸

In comparison, 60 percent of pale- but non-red-haired (blonde) individuals bear one dysfunctional MC1R allele, while fewer than 20 percent of individuals with darker hair and skin (skin type >2) show one dysfunctional allele.⁵ Basal MC1R signaling is preserved by the constitutive activity of the receptor and/or constitutive levels of agonist (e.g., autocrine) secretion of alpha-MSH, while UVR represents the main adaptive or environmental stimulus, increasing eumelanin formation, which is clinically visible as tanning.^8,9 While exposure of the skin to UV light damages the skin's DNA and increases the risk for skin cancer, it also initiates the tanning process resulting in increased melanin production, which in turn helps protect (although imperfectly) the skin cells from further photodamage. It also reduces generation of reactive oxygen species (free radicals), and is thought to enhance DNA repair in melanocytes, thereby enhancing their genomic stability and antagonizing malignant transformation to melanoma.^10-13

There is increasing evidence that melanomagenesis is driven not only by UVB-dependent mutagenesis, but also by reactive oxygen species (ROS), with pheomelanin likely playing an important role. Dysplastic nevi have been shown to carry higher pheomelanin levels and express more reactive oxygen radicals than normal human melanocytes.¹⁴ It has also been posited that the common somatic BRAF (V600E) mutation may occur via the action of oxygen radicals.¹⁵

Melanomagenesis Without UV

In 2012, Mitra, et al¹⁶ showed that pheomelanin synthesis even promotes melanoma formation in a UV radiation-independent context. Using a conditional allele of the melanoma oncoprotein BRAF V600E in red-haired mice carrying an inactivating mutation in the MC1R gene, Mitra's team observed a high incidence of invasive melanomas compared to genetically matched black mice (MC1R wild-type). Introduction of an albino allele, which deleted all pigment production, actually conferred protection against melanoma development in the UVR-free context. Correspondingly, skin of BRAF-mutant red animals showed significantly higher oxidative DNA and lipid peroxidation damage than skin from genetically matched albino-red mice—all in the complete absence of any measurable UVB or UVA exposure. Recognition of this pheomelanin-dependent oncogenic process of melanoma development via ROS called into question the currency and effectiveness of sunscreen and other accepted forms of sun protection, as well as clinical screening methods and melanoma therapies, in those with mutant MC1R.

How Does Pheomelanin Contribute to Melanoma?

In 2013, Morgan, et al suggested that pheomelanin might either enhance ROS generation directly or deplete major antioxidants.¹⁷ Subsequently, Panzella, et al investigated the effect of red human hair pheomelanin (RHP) on cellular redox systems, exploring autoxidation of GSH (glutathione), the most important cellular antioxidant, and NADH (nicotinamide adenine dinucleotide), a central component of the respiratory chain.¹⁸ They showed that GSH and NADH, considered critical indices of metabolic state and intracellular redox levels, were significantly decreased by pheomelanin. As it did not affect superoxide dismutase (SOD) and catalase (CAT), they assumed that pheomelanin does not produce significant levels of ROS measured with a variety of methods, including electron paramagnetic resonance (EPR) and spin trapping or colorimetric assays, but can induce depletion of GSH and NADH by a UV- and ROS-independent pathway. They assumed that pheomelanin can serve as a redox catalyst accepting H-atoms from the substrates and transferring electrons to oxygen.

Operation of a direct H-atom transfer to pheomelanin was confirmed by EPR analysis, showing a selective decrease in the pheomelanin signal in purified red hair pigment following incubation with excess GSH.¹⁸ This raised the hypothesis of pheomelanin as a "living" polymer and biocatalyst, which may trigger autoreactive prooxidant processes. In this mechanistic scheme, ROS would be produced from reoxidation of pheomelanin by oxygen but would be immediately utilized in the redox cycle.¹⁹ Nevertheless, it has not been fully determined whether MC1R exerts its oncogenicity via pheomelanin only or also by controlling different redox genes, such as the base excision repair enzymes 8-oxoguanine DNA glycosylase (OGG1) and the DNA damage repair enzyme apurinic apyrimidinic endonuclease 1 (APE-1/Ref-1).¹¹ In addition, the prooxidant activity of pheomelanin on UV-induced liposomal lipid peroxidation has been suspected to originate from pheomelanin-metal complexes.²⁰

The oncogenic effect of oxidative stress on cancer development has been shown for multiple tumors, such as liver, lung, breast, and skin cancers. ROS are short-lived entities that are continuously generated at low levels during the course of normal aerobic metabolism, likely playing the role of a second messenger. Skin exposure to ionizing and UV radiation, and/or xenobiotics, generates ROS in excessive quantities that may overwhelm cutaneous antioxidant reserves. This may expose the nucleus and other cellular organelles in the cytosol to high levels of oxidative stress. In skin, uncontrolled release of ROS is involved in the pathogenesis of a number of human skin disorders, especially cutaneous neoplasia. Within cells, ROS induce cell cycle alterations, DNA structural alterations including DNA strand breaks, DNA-protein crosslinks, and alterations of the mitogen-activated protein kinase (MAPK) pathway, as well as effects on lipid peroxidation and modulation of transcription factors such as activator protein 1 (AP-1) and nuclear factor κB (NF-kB).^21,22 Additional effects on the tumor microenvironment and immune system were alterations in Th1 and Th2 response patterns as well as changes in dendritic cell surface markers.²¹

What Can Sunscreens Do?

Sunlight reaching the Earth's surface is composed of differing wavelengths of the electromagnetic spectrum, ranging from infrared to visible and UV light. The UVB and UVA spectrum, between 280 nm and 400 nm, seems to be the most damaging light to our skin. UVA, with its longer wavelengths, can penetrate into deeper layers of the skin than UVB, with more rays penetrating the basal epidermis cells where melanocytes are located. Mathematical models predict that regular sunscreen use may greatly reduce the lifetime incidence of nonmelanoma skin cancers, and studies have clearly shown this with cutaneous squamous cell carcinoma²³—yet results with respect to melanoma incidence have been somewhat more complex.

Even though comprehensive review of all studies from 1966 to 2003 found no evidence that sunscreen increases melanoma risk,^24,25 the question of how efficient sunscreens really are in melanoma prevention was not fully demonstrated until 2010, when a randomized controlled human trial showed that sunscreens can indeed prevent melanoma formation.²⁶ Green and colleagues demonstrated a ~50% reduction in melanoma incidence after long-term follow-up of 1,621 Australian individuals randomized to daily SPF 16 sunscreen application to head, neck, arms, and hands. In this study, performed at a low-latitude township in Australia, the control group was also allowed "discretionary" use of sunscreen, but was not guided concerning type or application frequency. Overall, this clinical study demonstrated that sunscreen application can help prevent melanoma formation, but also highlighted the need for consistent rather than intermittent use.²⁶ In 2014, Viros, et al showed that a broad-spectrum sunscreen applied on mice expressing BRAF(V600E) delayed the onset of UVR-driven melanoma, but only provided partial protection.²⁷

Although both studies validated public health campaigns promoting sunscreen protection for individuals at risk of melanoma, it is becoming clear that current sunscreens and prevention guidelines might not be sufficient to fully prevent the disease. An ideal sunscreen would protect against 100 percent of all UVR wavelengths and offer long-term protection without reapplication, but such a sunscreen does not yet exist.²⁸

A factor traditionally used, and broadly publicized, to evaluate sunscreen efficacy is the sun protection factor (SPF), defined as the ratio of UVR required to produce minimal erythema/sunburn with sunscreen, compared to without sunscreen. It is important to understand that the SPF endpoint is not a measure of skin cancer risk, but of propensity to induce skin erythema. Overall, an individual's protection against sunburn depends on that individual's capacity to generate erythema, a clinical feature usually mediated by UVB exposure. But no matter how high the SPF value is, the efficacy of a sunscreen also depends on the amount applied, the frequency of reapplication, and the Fitzpatrick skin phototype of the individual. For example, in calculating SPF, the US Food and Drug Administration (FDA) uses a dose of 2.2 mg/cm² of exposed skin, applying the sunscreen 30 minutes before UV exposure. However, in practice, most people do not follow these guidelines, usually applying only one-quarter of the recommended dose.^29,30

Furthermore, it is becoming clear that UVA plays a significant role in melanoma formation. It may potentiate the carcinogenic effects of UVB and is known to stimulate generation of ROS within the skin. So far only three UVA absorbers are FDA-approved in the US, whereas seven are available in Europe. Among the UVA filters approved in Europe are three – Tinosorb S, Tinosorb M, and Mexoryl SX – whose safety has been studied for years in Europe, and which are between 3.8 and 5.1 times more UVA-protective than the maximum allowable concentration of avobenzone, the most common UVA filter in US products.³¹

Some years ago US sunscreen makers began seeking FDA approval to use some of these compounds, but approval has not yet been granted. Newer sunscreen products attempt to filter both UVA and UVB spectra. However, half of all sunscreens advertised to offer "broad spectrum" UVA/UVB protection provide only low or medium UVA protection.³² It is therefore important to continue emphasizing the importance of additional sun safety measures, such as sun avoidance, shade, clothing, and sunglasses.

Another challenge of uncertain relevance is the impact of sunscreens themselves on ROS formation in skin. Mostly limited to a small number of solution-phase and in vitro studies, para-aminobenzoic acid (PABA) and 2-phenyl-benzimidazole-5-sulfonic acid (PBSA) have been described to induce both singlet oxygen (1O2) and thymine-dimer formation.^33-35 Solution-phase studies found that octylmethoxycinnamate, octocrylene, and PABA all produce 1O2 in phosphate-buffered saline.^33,35

In 2006, Hanson, et al used the fluorescent ROS indicator dihydrorhodamine (DHR) to measure generation of oxidative stress after topical application of oxybenzone, octocrylene, and octinoxate on human ex vivo skin and an epidermal skin model.³⁶ Two-photon fluorescence microscopy revealed that even though early time points showed decreased ROS formation after 60 minutes of incubation, oxidative stress increased. In addition, in vitro experiments using zinc oxide nanoparticles showed increases of oxidative stress and decreased viability in melanoma cells.^37,38

Overall, in most real-life situations, it seems very likely that the net effect of sunscreen use is to reduce net free radical formation due to its UV-filtering benefits. But several concerns would suggest that even greater efficacy might be achieved through certain considerations. As discussed above, cell-intrinsic pheomelanin has been associated with increased ROS production. For individuals who tan easily in response to UV exposure, their pheomelanin/eumelanin ratio is predicted to be increased by consistent sunscreen usage. This would suggest that there may be a "ceiling" to the magnitude of protection offered by UV filters, determined in part by intrinsic melanin pigments within an individual's skin. Additionally, formation of free radicals by the UV-absorbing chemical species, still likely preferable to UV exposure, may nonetheless limit the magnitude of protection afforded by these agents. Clearly, additional detailed studies are needed to more fully understand mechanisms of action and any limitations of highly used skin care products, as well as to develop agents that optimally protect against both UV and oxidative genotoxic damage.

What Does This Mean for Physicians and Patients?

Since the Australian SunSmart campaign with its slogan "slip/slop/slap/seek/slide" was introduced in 1988, many people have been convinced to slip on a long-sleeved top, slop on sunscreen, slap on a hat, seek shade and slide on sunglasses. What has changed since then?

As sunlight remains one of the top risk factors for development of cutaneous melanoma, rigorous sun protection remains the main goal. This includes avoidance of direct sun exposure in peak hours, seeking shade, use of covering clothes, a broad-brimmed hat, and sunglasses. While sunscreen use remains a vital recommendation for skin cancer prevention, we might rethink the concept of sunscreens as being equivalent to physical sun protection. Sunscreen ingredients remain chemicals with the potential risk—as any other skin care product—to increase oxidative damage in skin. Optimizing both the safety and efficacy of these ingredients is not a trivial task, as their effects may vary for individuals of different skin phototypes.

Current evidence suggests that naturally pigmented skin (not pigmented by UV exposure) is one of the best available skin cancer "sunscreens," providing up to a 50-fold decrease in the risk of basal and squamous cell carcinomas, and a 12-fold decrease in the risk of melanoma³⁹— benefits not to date achieved or measurable with sunscreen usage. Natural skin color in darker-pigmented individuals of skin type > 2, not resulting from UV exposure, may offer significant protection from typical daily sunlight exposure through its direct shielding and antioxidant features. However, the situation is very different in individuals with pale skin types 1 and 2. This population, with poor tanning dose/response to UV resulting in oncogenic mutational events, bears a greatly increased risk of developing melanoma.

Antioxidants vs. Pheomelanin

The concept of adding antioxidants into sunscreens is attractive yet potentially controversial. While antioxidants diminish oxidative stress through their direct chemical actions, they may also increase cellular cysteine levels due to sparing of endogenous cellular antioxidant consumption. This could be important because cysteine is one of the key ingredients in the pheomelanin synthesis pathway. Therefore, addition of antioxidants might indeed decrease ROS at early time points due to direct chemical quenching, but later switch the pigmentation pathway from eumelanin towards pheomelain synthesis, thereby indirectly contributing to pheomelanin's prooxidative effect. It has been shown that cysteine deprivation promotes eumelanogenesis in human melanoma cells,⁴⁰ and that correspondingly, oral administration of gluthatione induces skin lightening/depigmentation.⁴¹

Such effects are, however, complex, and are likely to depend significantly on chemical details of the antioxidant species, the skin's intrinsic antioxidant features, and the skin's pigmentation status. Further research on sunscreens is needed to develop non-ROS-generating products that are both safe and efficient. Possibilities include introducing chemical step-down processes, finding non-cysteine-modifying antioxidants, or discovering a safe way to induce skin pigmentation. Further investments by manufacturers and researchers alike in sunscreen research and enhanced approval processes are also greatly needed. This includes efforts to promote faster FDA approval of safe, effective sunscreens.

In the meantime, sunscreen use remains strongly recommended, for prevention not only of melanoma but of squamous cell carcinoma and benign skin damage including photoaging. Furthermore, skin type 1 and 2 individuals should minimize sun exposure and avoid tanning, and should utilize physical sun protection as much as possible. All individuals, especially those at high-risk, should regularly visit an experienced physician trained in skin examination and practice rigorous self-examination routinely. Overall, personalizing skin cancer protection and early melanoma detection based on an individual's skin type might help to stem the relentless morbidity and mortality of melanoma.

References

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17. Morgan AM, Lo J, Fisher DE. How does pheomelanin synthesis contribute to melanomagenesis?: Two distinct mechanisms could explain the carcinogenicity of pheomelanin synthesis. BioEssays: news and reviews in molecular, cellular and developmental biology 2013; 35(8):672-676.
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37. Wahab R, Dwivedi S, Umar A, et al. ZnO nanoparticles induce oxidative stress in Cloudman S91 melanoma cancer cells. J Biomed Nanotechnol 2013; 9(3):441-449.
38. Alarifi S, Ali D, Alkahtani S, et al. Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. Int J Nanomedicine 2013; 8:983-993.
39. Hearing VJ. The melanosome: the perfect model for cellular responses to the environment. Pigment Cell Res 13 Suppl 8:23-34, sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society 2000.
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Painful Hands and Feet After Cancer Treatment: Inflammation Affecting the Mind-Body Connection

American Society of Clinical Oncology, 2318 Mill Road, Suite 800, Alexandria, VA 22314

Journal of Clinical Oncology® is a trademark of the American Society of Clinical Oncology

To read the full research article, select the hyperlink.

Tags: pain, hands, feet, inflammation, mind-body connection, breast cancer, fatigue, peripheral neuropathy

The three most common persistent symptoms after cancer treatments are fatigue, cognitive dysfunction, and peripheral neuropathy, and these have all been linked to neuroinflammation,4,6,7 as well as genetic susceptibility to persistent inflammation and behavioral symptoms.30-33 Given the important role of inflammation in association with cancer treatments, there is the possibility of developing anti-inflammatory strategies that may mitigate or modify these post-treatment symptoms. These symptoms are often co-occurring, as we have seen in our studies of fatigue and cognitive dysfunction, and may be directly related to elevation of pro-inflammatory cytokines after treatment that are correlated with cerebral metabolism, with the inflammation gradually declining in the year after cancer treatment ends.34-37 In addition, some individuals may be predisposed to these symptoms before the initiation of cancer therapy, as has been shown with CIPN-sx and cognitive dysfunction,38,39 suggesting the potential to identify high-risk individuals in whom preventive strategies should be considered. Furthermore, understanding mechanisms associated with pretreatment risk of CIPN may contribute to understanding post-treatment sequelae. The key point arising from this body of research is that these symptoms can now be measured successfully with a wide variety of well-validated self-report tools and that patient-reported outcomes are significantly associated with cerebral effects measured by a variety of techniques. We must be clinically attuned to the complaints our patients voice, and we must make a serious effort to develop prevention and treatment strategies that will reduce the burden of cancer treatment–associated toxicities.

AUTHOR CONTRIBUTIONS

Manuscript writing: All authors

Final approval of manuscript: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Painful Hands and Feet After Cancer Treatment: Inflammation Affecting the Mind-Body Connection

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.

Patricia A. Ganz

Leadership: Intrinsic LifeSciences (I)

Stock or Other Ownership: xenon (I), Intrinsic LifeSciences (I), Silarus Therapeutics (I), Merganser Biotech (I), Teva Pharmaceuticals, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott Laboratories

Consulting or Advisory Role: Keryx Biopharmaceuticals (I), Merganser Biotech (I), Silarus Therapeutics (I), InformedDNA

Research Funding: Keryx Biopharmaceuticals (I)

Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease (I), Up-to-Date royalties for section editor on survivorship

Travel, Accommodations, Expenses: Intrinsic LifeSciences (I), Keryx Biopharmaceuticals (I)

Patrick M. Dougherty

Consulting or Advisory Role: Takeda Pharmaceuticals, Daiichi Sankyo

See accompanying article on page 677

REFERENCES

Section:

COMPANION ARTICLES

No companion articles

ARTICLE CITATION

DOI: 10.1200/JCO.2015.64.7479 Journal of Clinical Oncology 34, no. 7 (March 2016) 649-652.

PMID: 26700128

Neuropathy

Neuropathy is different for every person. The symptoms and their severity depend on which nerves are damaged and how many nerves are affected.

Tags: neuropathy, breast cancer, pain, peripheral nerves,

Symptoms may develop during or shortly after cancer treatment. Neuropathy may also develop slowly or worsen after treatment has ended. This occurs most commonly with platinum drugs and drugs called taxanes.

Damage may occur in the 3 types of peripheral nerves:

1. Sensory nerves. These affect your sense of feeling. Symptoms in hands and feet when sensory nerves are affected:

Tingling, burning, a buzzing "electricity" sensation, or numbness. It usually starts in the toes and fingers. It can continue along the hands and feet toward the center of the body.

Pain, usually described as pinching, sharp stabs, burning, and electrical shocks.

A feeling like wearing tight gloves or stockings.•An uncomfortable sensation that may get worse when you touch something.

Pain from objects that aren't usually painful. For example, shoes or bedcovers.

Difficulty feeling hot and cold temperatures or knowing if you've injured yourself.

Difficulty knowing where your feet and hands are in space. This is called loss of position sense. It may make walking or picking up objects more difficult, particularly in a dark room or when working with small objects.

2. Motor nerves. Motor nerves send information between your brain and muscles. Injured motor nerves may cause these symptoms:

Trouble walking and moving.

A feeling of heaviness or weakness in the legs and arms. This may cause balance and coordination problems.

Difficulty using the hands and arms.

Trouble with everyday tasks. Particularly fine motor skills, such as texting or buttoning a shirt.

Muscle cramps and muscle loss in the hands and feet.

3. Autonomic nerves. These nerves control the body functions you don't control consciously. These include blood pressure and bowel and bladder function. These symptoms may occur with damage to autonomic nerves:

An inability to sweat normally

Gastrointestinal problems, such as diarrhea and constipation

Dizziness or lightheadedness

Trouble swallowing

Sexual problems

Talk with your health care team about your symptoms. Include new ones and changes in symptoms. Ask about strategies to manage them.

Managing neuropathy. Relieving side effects is an important part of cancer care. This is called palliative care or supportive care. Treatment for peripheral neuropathy depends on the cause and symptoms. Many people fully recover a few months or years after treatment. However, sometimes, the condition requires long-term management.

Peripheral neuropathy treatment options:

Medication. Although medication cannot cure neuropathy, it may relieve the pain. However, it doesn't relieve numbness. Prescription nonsteroidal anti-inflammatory drugs or analgesics are options for severe pain. Analgesics are very strong painkillers. Topical treatments may also help control pain. These include lidocaine patches and creams. Topical 1% menthol also seems helpful, based on early studies. Additionally, your health care team may recommend over-the-counter medications for mild pain.

Better nutrition. Eating a diet rich in specific nutrients may help manage neuropathy. Examples:

B vitamins, including B1 and B12

Folic acid

Antioxidants

Also try to eat a balanced diet.

Avoid drinking too much alcohol.

Physical or occupational therapy. Physical or occupational therapy helps keep muscles strong. It also improves coordination and balance. Therapists sometimes recommend devices that help with daily activities.

Mind-body exercises, such as tai chi or qigong, can help improve balance. Additionally, regular exercise may help reduce pain.

Devices that stimulate the skin with electricity may help, too. However, more research is needed.

Integrative medicine. These complementary therapies may help reduce pain and mental stress:

Massage

Acupuncture

Acupressure

Relaxation