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Author Topic: Vitamin D deficiency in Leukemia?  (Read 233465 times)

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #250 on: 29/06/2010 22:04:31 »
Searching for D-vitamin & leukemia connections...


Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity.



Slominski AT, Janjetovic Z, Fuller BE, Zmijewski MA, Tuckey RC, Nguyen MN, Sweatman T, Li W, Zjawiony J, Miller D, Chen TC, Lozanski G, Holick MF.

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America. aslominski@uthsc.edu

Abstract
BACKGROUND: Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)(2)D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3 (1,20(OH)(2)D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL).
METHODS AND FINDINGS: To define the biological significance of these P450scc-initiated pathways, we tested the effects of their 5,7-diene precursors and secosteroidal products on leukemia cell differentiation and proliferation in comparison to 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D3). These secosteroids inhibited proliferation and induced erythroid differentiation of K562 human chronic myeloid and MEL mouse leukemia cells with 20(OH)D3 and 20,23(OH)(2)D3 being either equipotent or slightly less potent than 1,25(OH)(2)D3, while 1,20(OH)(2)D3, pD and pL compounds were slightly or moderately less potent. The compounds also inhibited proliferation and induced monocytic differentiation of HL-60 promyelocytic and U937 promonocytic human leukemia cells. Among them 1,25(OH)(2)D3 was the most potent, 20(OH)D3, 20,23(OH)(2)D3 and 1,20(OH)(2)D3 were less active, and pD and pL compounds were the least potent. Since it had been previously proven that secosteroids without the side chain (pD) have no effect on systemic calcium levels we performed additional testing in rats and found that 20(OH)D3 had no calcemic activity at concentration as high as 1 microg/kg, whereas, 1,20(OH)(2)D3 was slightly to moderately calcemic and 1,25(OH)(2)D3 had strong calcemic activity.

CONCLUSIONS: We identified novel secosteroids that are excellent candidates for anti-leukemia therapy with 20(OH)D3 deserving special attention because of its relatively high potency and lack of calcemic activity.

PLoS One. 2010 Mar 26;5(3):e9907







Quote

Vitamins versus leukemia
Vitamins A and D may stop cancer cells from growing

by Joseph Briante

Vitamins that can "steer" cancer cells away from growth toward cell differentiation or cell death may form the basis of new therapies for fighting leukemia, say University of Guelph researchers.

Profs. Kelly Meckling-Gill and Jim Kirkland, graduate student Donna Berry and post-doctoral fellow Ducica Curdic, Department of Human Biology and Nutritional Sciences, have discovered a vitamin D signalling pathway that affects how cancer cells grow and develop.

They're now looking at a combination of vitamins A and D to combat acute promyelocytic leukemia (APL), which accounts for about 10 per cent of leukemia cases.

Vitamins A and D may also have preventive activity in inhibiting leukemia development in the "at risk" population.

"If we treat leukemia cells with both (Vitamin A and D), those cells are induced to die at a high rate," says Meckling-Gill. "And the vitamins may have a role in preventing cancerous development."


THE APL CHALLENGE
APL usually strikes adults in the prime of their life, with a median age of about 35. Traditional chemotherapy is effective, but relapses are common and very aggressive. So physicians use another approach known as differentiation therapy, which uses an agent to force immature cancer cells to mature and, at the same time, inhibits their growth.
One such agent, retinoic acid -- an active metabolite of vitamin A -- has already been used clinically to treat APL. But its use is limited because it has only short-term efficacy, and patients generally develop resistance.

The Guelph researchers hope that a dual attack using calcitriol, the active form of Vitamin D, and retinoic acid will improve the efficacy of differentiation therapy. If this happens, a treatment could be developed to use when retinoic acid fails.

Meckling-Gill has shown that when calcitriol is used, APL cells mature normally in a pathway distinct from the one induced by retinoic acid. APL cells are arrested at a point where they would normally choose between two maturation pathways. Retinoic acid stimulates maturation to neutrophils; and calcitriol, to monocytes and macrophages, cell types important for immune function.

"A patient resistant to retinoic acid may still respond to vitamin D," says Meckling-Gill. "We hope this research will contribute to the design of a drug to use in a clinical setting."


A MORE GENTLE THERAPY

The advantage of vitamin-derived treatment is that it could decrease problems associated with immunosuppressive and chemotherapeutic drugs, which often have very toxic side effects. If effective, differentiation therapy eliminates the need for patients to undergo bone marrow transplants, which are risky and costly.

This research is sponsored by the Natural Sciences and Engineering Research Council and the Cancer Research Society Inc.



Fall 1998!!!   10 years after the "Shanghai Report"!
 http://www.uoguelph.ca/research/publications/Assets/HTML_MAGS/health/page35.html



« Last Edit: 13/01/2011 12:30:59 by iko »
 

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #251 on: 01/11/2010 14:26:15 »
Time is flowing fast, reports about vit.D
deficiency are many: this one is about post-
-bone marrow transplant pediatric patients:
mostly leukemic patients, of course.


25-Hydroxy Vitamin D Deficiency Following Pediatric Hematopoietic Stem Cell Transplant.


Duncan CN, Vrooman L, Apfelbaum EM, Whitley K, Bechard L, Lehmann LE.
Dana-Farber Cancer Institute, Boston, MA 02115, United States.

Children may be at increased risk for vitamin D deficiency following HSCT due to lack of sun exposure, the recommended use of sunscreen, dietary insufficiency, malabsorption, and the use of certain medications. We prospectively assessed the prevalence of and risk factors for 25-hydroxy (OH) vitamin D deficiency in 67 patients transplanted at our institution. 25-OH vitamin D levels were checked during three separate four week periods in the spring, autumn, and winter. Subjects were less than two years following transplant and/or being treated for chronic GVHD. Levels less than 20 ng/mL were considered deficient and those less than 30 ng/mL were considered insufficient. The mean 25-OH vitamin D level was 22.8 ng/mL (range 7- 46.2). 80.6% (CI 69.1- 89.3%) of patients had a level less than the lower limit of the institutional normal range. The deficiency rate was 37.3% (CI 25.8-50%). The mean parathyroid hormone (PTH) level was 77.5 (SD 80.5). There was no correlation between 25-OH vitamin D and PTH levels. We evaluated potential risk factors for 25-OH vitamin D deficiency including age, season of testing, sun exposure, sunscreen use, use of steroid or calcineurin inhibitor, race, and dairy intake. In multivariate logistic regression, only older age was found to be a risk factor for deficiency (p=0.004). Patients with deficient levels were treated with 50,000 IU of ergocalciferol once weekly for six weeks. A post-repletion 25-OH level was available for 22 patients. The majority of repleted patients had a normal post-treatment level (63.6%). The post-supplementation level corrected into the insufficient range for 31.8% of patients and 4.6% remained deficient.

 Vitamin D insufficiency and deficiency are common following HSCT. Further investigation into potential risk factors and the appropriate supplementation for these patients is warranted.

Biol.Bone Marrow Transplant   2010 Oct.14




« Last Edit: 01/01/2011 13:58:21 by iko »
 

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #252 on: 27/12/2010 11:10:26 »
Freshly published. From Rochester, Minnesota, USA.
Almost 22 years after the 'Shanghai Report'.




Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia (CLL).


Shanafelt TD, Drake MT, Maurer MJ, Allmer C, Rabe KG, Slager SL, Weiner GJ, Call TG, Link BK, Zent CS, Kay NE, Hanson CA, Witzig TE, Cerhan JR.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States;

Abstract
Vitamin D insufficiency is common globally with low levels linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment(TTT) and overall survival(OS) in newly diagnosed CLL patients participating in a prospective cohort study(discovery cohort) and a separate cohort of previously untreated patients participating in an observational study(confirmation cohort). Of 390 CLL patients in the discovery cohort, 119(30.5%) were 25(OH)D insufficient. After median follow-up of 3 years, TTT(hazard ratio[HR ]=1.66; p=0.005) and OS(HR=2.39; p=0.01) were shorter for 25(OH)D insufficient patients. In the validation cohort, 61 of 153 patients(39.9%) were 25(OH)D insufficient. After median follow-up of 9.9 years, TTT(HR=1.59; p=0.05) and OS(HR 1.63; p=0.06) were again shorter for 25(OH)D insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, stage, CD38, ZAP-70, IGHV, CD49d, and FISH, 25(OH)D insufficiency remained an independent predictor of TTT(HR=1.47; p=0.008), although the association with OS was not significant(HR=1.47; p=0.07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.

Blood. 2010 Nov 3. [Epub ahead of print]

PMID: 21048153



« Last Edit: 05/01/2011 21:16:24 by iko »
 

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #253 on: 08/01/2011 13:02:22 »
Hey!
Somebody just found the ancient "Shanghai Report" searching PubMed...
...and surprisingly didn't think to cross leukemia and 'cod' on Google!




...and now, if you Google "leukemia cod" these two 'pieces of information'
come first and second out of 245k citations! I love this new global Era...
and I'd like to celebrate with you all. Stand up and dance:




Playing for Change is a multimedia movement created to inspire, connect, and bring peace to the world through music. It creates music all over the world to make money to build music and art schools in communities that are in need of inspiration and hope.
Based on the belief that music has the power to break down boundaries and overcome distances between people, Playing for Change set out to make music by gathering musicians from all over the world and bringing their music to the masses. Their efforts clearly proves that music is the same throughout the world.
Chanda Mama is a folk song from India about the moon. Playing for Change made the Chanda Mama video with a group of talented musicians such as Tula (Israel), Noel Schajris (Argentina), Paolo Morais (Portugal), Roberto Luti & Stefano Tomaselli (Italy), Oneness Choir (India), choir Sinamuva & Sibongiseni Mbanjwa (South Africa), Marcelo "Gaucho" & Santiago Maggi (Argentina), Damien Issertes (France), to name a few.

Here are the lyrics and the English translation as can be found on www.songlyrics.com

Chanda mama raavayya : Moon please come
Nannu yetthukoni muddhuladi povayya : Hold me and kiss me and go
Maraalu nenenni chesina : Thou I always sulked and made petty demands
Gaaralyu neeve chupina: YOu always returned your TLC (tender loving care) and pampered me

"This Song Around The World is a folk tune that originated in Chennai, India. We started the track in New Orleans and added musicians from the all over the world before finally delivering it the people of its origin. We ended up in Chennai recording and filming vocals by the Oneness Choir. The result is an uplifting track that has a feeling of perseverance and joy." - Playing for Change


« Last Edit: 08/01/2011 14:10:07 by iko »
 

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #254 on: 13/03/2011 17:44:38 »

"...From a clinical perspective, vitamin D insufficiency represents the first potentially modifiable prognostic marker in chronic lymphocytic leukemia (CLL) by presenting the opportunity for patients to have their serum vitamin D checked and, if they are deficient, vitamin D supplements administered to correct the deficit."

...

CLL: a supplementary question?


Pepper C, Fegan C.
Cardiff University.

Comment on:
Blood. 2011 Feb 3;117(5):1492-8.

Abstract
In this issue of Blood, Shanafelt and colleagues provide the first evidence that vitamin D deficiency is a risk factor for disease progression in chronic lymphocytic leukemia (CLL). Their findings imply that dietary vitamin D supplementation could potentially modify the natural history of this incurable disease.

Blood. 2011 Feb 3;117(5):1439-40.




« Last Edit: 17/03/2011 00:06:38 by iko »
 

Offline iko

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Re: Vitamin D deficiency in Leukemia?
« Reply #255 on: 21/03/2011 18:31:03 »
Ok, we seem to be almost THERE.

It's a pity we didn't start from childhood leukemias...they are not incurable, in fact, but curable in the majority of patients (well over 50%), not enough though.
 
 
"To see what is in front of one's nose needs a constant struggle." George Orwell



If, in the near future, proper vitamin D3 supplementation improves survival in childhood leukemias...
  Well...I'm going to take a week off, a month off...maybe a whole year off!

Ikod















...and that's it my friends,
I thank you so much for your interest
in such a neglected area of human research.

Ikod
« Last Edit: 10/05/2011 20:46:41 by iko »
 

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Re: Vitamin D deficiency in Leukemia?
« Reply #255 on: 21/03/2011 18:31:03 »

 

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