CANCER

In this section we will provide scientific studies related to the ingredients contained in the NMS Neuromuscular Support Formula that deal with Cancer. This is additional information that we feel relates to the efficacy of this amazing product and should also give you an idea of the breadth and scope of the information about the ingredients in the NMS Formula dealing with health conditions other than Pain & Inflammation.

CANCER --- THIAMINE

Oncology. 2009;76(1):10-8. Epub 2008 Nov 19.
Wernicke's encephalopathy: an underrecognized and reversible cause of confusional state in cancer patients.
Kuo SH, Debnam JM, Fuller GN, de Groot J.
Department of Neurology, Baylor College of Medicine, USA.

BACKGROUND: Wernicke's encephalopathy (WE) is a neurological emergency which presents with symptoms of confusion, ophthalmoplegia, and ataxia. Cancer patients are at high risk of this acute encephalopathy due to chronic malnutrition, chemotherapy-induced nausea and vomiting, and consumption of thiamine by rapidly growing tumors. A high index of suspicion is important as these critically ill patients may not present with the classic triad of symptoms. METHODS: This study is a retrospective review of 5 patients with WE identified at M.D. Anderson Cancer Center, Houston, Tex., USA. Detailed clinical histories, risk factors, imaging, and histopathological characteristics are described. RESULTS: Five WE patients were identified and all patients had rapidly growing cancers and were undergoing active treatment. All patients had poor nutritional status due to chronic nausea from chemotherapy. Three patients received bone marrow transplantation (BMT). Acute confusion was the most common symptom. Magnetic resonance imaging studies of the brain revealed restricted diffusion and fluid attenuation inversion recovery sequence hyperintensity in the medial thalami and periaqueductal gray matter. In 2 cases, WE was considered antemortem, and only 1 was empirically treated with thiamine, which rapidly reversed the imaging findings within 7 days and led to clinical improvement. Other cases were diagnosed at autopsy. CONCLUSION: It is crucial to consider WE in the differential diagnosis for all cancer patients with confusion. Cancer patients with malnutrition and patients with BMT are at high risk of developing WE. To prevent this devastating and often fatal neurologic complication, all cancer patients with confusion should be empirically treated with thiamine.

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Neurosci Bull. 2009 Apr;25(2):94-9.
A review on research progress of transketolase.
Zhao J, Zhong CJ.
Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032.

Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of non-oxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the interface between the contacting monomers. Both ThDP and bivalent cations are strictly needed for TK activation, just like that for all ThDP-dependent enzymes. TK exists in all organisms that have been investigated. Up to now, one TK gene (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in human genome. TKTL1 is reported to play a pivotal role in carcinogenesis and may have important implications in the nutrition and future treatment of patients with cancer. Researchers have found TK variants and reduced activities of TK enzyme in patients with neurodegenerative diseases, diabetes, and cancer. Recent studies indicated TK as a novel role in the prevention and therapy of these diseases.

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South Med J. 2007 Jul;100(7):717-9
Wernicke encephalopathy complicating lymphoma therapy: case report and literature review.
Boniol S, Boyd M, Koreth R, Burton GV.
Feist-Weiller Cancer Center, Louisiana State University Health Science Center, Shreveport, LA 71130, USA.

Thiamine deficiency can occur in any disease that results in inadequate intake or excessive loss of vitamin B1. In addition to increased thiamine consumption secondary to high cell turnover, cancer patients frequently have reduced oral intake as a direct result of their cancer or from cancer treatments. However, Wernicke encephalopathy (cerebral Beriberi), a clinical manifestation of thiamine deficiency, has rarely been associated with cancer patients. We report a case of Wernicke encephalopathy in a nonalcoholic patient with lymphoma. Although thiamine deficiency rarely potentiates clinical sequelae in cancer patients, it is important to recognize the risk and the clinical signs and manifestations so that prompt therapy can be initiated to reverse morbidity.

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Oncol Rep. 2007 Apr;17(4):841-5.
Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer.
F�ldi M, Stickeler E, Bau L, Kretz O, Watermann D, Gitsch G, Kayser G, Zur Hausen A, Coy JF.
Department of Obstetrics and Gynaecology, University Hospital Freiburg, D-79106 Freiburg, Germany.

Malignant tumors degrade glucose to lactate even in the presence of oxygen via the pentose phosphate pathway (ppp). The non-oxidative part of the ppp is controlled by thiamine-dependant transketolase enzyme reactions. Overexpression of the transketolase-like-1-gene (TKTL1) in urothelial and colorectal cancer is associated with poor patient outcome. We analyzed the expression of the TKTL1 protein in a retrospective institution-based patient cohort with invasive breast cancer by immunohistochemical analysis of 124 paraffin-embedded breast cancer tissues. Our study revealed TKTL1 expression in 86% of breast cancer specimens with 45% showing high expression levels. In contrast, only 29% of corresponding non-neoplastic breast tissues were TKTL1 immunopositive, including 9% with high expression levels. High expression levels of TKTL1 correlated significantly to Her2/neu overexpression (p=0.015). However, TKTL1 expression failed to reach statistical significance for other common prognostic parameters. In contrast to recent data for e.g. colorectal cancer TKTL1 overexpression did not correlate to patient outcome and survival. However, in the context of novel insights into TKTL1-related tumor metabolism and the high proportion of TKTL1 overexpressing breast cancers, this enzyme represents a potential candidate for targeted inhibition of tumor growth in this tumor entity.

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Oncol Rep. 2005 Dec;14(6):1589-92
Thiamin deficiency: a possible major cause of some tumors? (review). Lee BY, Yanamandra K, Bocchini JA Jr.
Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, USA. blee1@lsuhsc.edu

Based solely on clinical clues from a malnourished population, thiamin alone was intentionally and successfully injected to human cases with some tumors or masses. Two cases of submandibular gland cyst and 13 out of 15 cases of Baker's cyst were cured without recurrence for several decades. In a case with pathology-confirmed osteosarcoma, subcutaneous perfusion of thiamin HCl 300 once only reduced its circumference from 30 to 20 cm, equivalent to a reduction of 50-75% in volume, within 2 days. Current concepts on the role of thiamin in carcinogenesis are controversial. Some authors claimed that thiamin supported high rate of tumor cell survival, proliferation and chemotherapy resistance and suggested anti-thiamin therapy for cancer. On the other hand, some investigators have reported evidence of prevention of several varieties of cancers by dietary thiamin. A limited number of animal studies revealed evident relationship between thiamin deficiency and cancer development. Therefore, further study on the mechanism switching thiamin between cancer supporter and suppressor is needed.

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CANCER --- VITAMIN B6

Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3233-40.

One-carbon metabolism biomarkers and risk of colon and rectal cancers.

Weinstein SJ, Albanes D, Selhub J, Graubard B, Lim U, Taylor PR, Virtamo J, Stolzenberg-Solomon R.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Nutritional Epidemiology Branch, Suite 320, 6120 Executive Boulevard, Bethesda, MD 20892, USA. weinstes@mail.nih.gov

BACKGROUND: Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers. METHODS: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression. RESULTS: Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk. CONCLUSIONS: Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer.

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J Nutr. 2007 Jul;137(7):1808-14.
Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men.
Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S;
Japan Public Health Center-based Prospective Study Group.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. We investigated the association of dietary intakes of folate, vitamin B-6, vitamin B-12, and methionine with the risk of colorectal cancer in a large prospective cohort study of middle-aged Japanese men and women. A total of 81,184 subjects (38,107 men and 43,077 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2002, during which 526 cases of colorectal cancer (335 men, 191 women) were newly identified. Dietary intake of nutrients was calculated using a 138-item self-administered FFQ. We observed a significant inverse association between vitamin B-6 intake and colorectal cancer in men. Compared with the lowest quartile, the multivariate hazard ratio (95% [CI]) in the highest quartile of intake was 0.69 (0.48-0.98) (P(trend) = 0.03). Men who consumed 150 g/wk alcohol or more had twice the risk of colorectal cancer of those who drank less in the lowest quartile of vitamin B-6 intake, but risk due to alcohol intake was not higher in the highest quartile of vitamin B-6 intake. Vitamin B-6 intake and colorectal cancer were not associated in women. Folate and methionine intakes were not associated with colorectal cancer risk in men or women, but colorectal cancer risk tended to increase (P(trend) = 0.05) with increasing intake of vitamin B-12 in men. Our results support previous evidence that low vitamin B-6 intake is associated with an increased risk of colorectal cancer. In particular, a higher intake of vitamin B-6 appears beneficial in men with higher alcohol intake.

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Nutr Hosp. 2007 Jan-Feb;22(1):7-24
Vitamin B6 status, deficiency and its consequences--an overview.
Spinneker A, Sola R, Lemmen V, Castillo MJ, Pietrzik K, Gonz�lez-Gross M.
Grupo Effects 262, Facultad de Medicina, Universidad de Granada, Spain.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

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Curr Opin Investig Drugs. 2006 Oct;7(10):912-5
Vitamins: not just for enzymes.
Bolander FF.
University of South Carolina, Department of Biological Sciences, Columbia, SC 29208, USA. bolander@sc.edu

Vitamins have traditionally played the role of coenzymes, organic molecules that facilitate the chemical reactions catalyzed by enzymes. However, several vitamins assume additional endocrine-like actions; this review will discuss four such vitamins. Vitamin K2 is involved in the gamma-carboxylation of coagulation factors and bone proteins, but it can also bind and activate the steroid and xenobiotic receptor in order to mediate transcription in bone tissue, and has been used to treat osteoporosis. Biotin is critical for some carboxylation reactions, but it also induces epidermal differentiation and has been used to treat lameness in animals and brittle nails in humans. Pyridoxal phosphate (the active form of vitamin B6) is involved in a multitude of reactions, including decarboxylation and transamination; it can also inhibit DNA polymerases and several steroid receptors and may prove useful as an adjunct in cancer chemotherapy. Finally, nicotinic acid is converted to NAD+ and NADP+, which are used as hydrogen/electron carriers in redox