WO2005013951A2 - Pharmaceutical compositions for preventing breast and ovarian cancer - Google Patents

Pharmaceutical compositions for preventing breast and ovarian cancer Download PDF

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Publication number
WO2005013951A2
WO2005013951A2 PCT/PL2004/000063 PL2004000063W WO2005013951A2 WO 2005013951 A2 WO2005013951 A2 WO 2005013951A2 PL 2004000063 W PL2004000063 W PL 2004000063W WO 2005013951 A2 WO2005013951 A2 WO 2005013951A2
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WO
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Prior art keywords
selenium
composition
breast
brcal
carriers
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PCT/PL2004/000063
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English (en)
French (fr)
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WO2005013951A3 (en
Inventor
Jan Lubinski
Steven Narod
Stanislaw Zajaczek
Elzbieta Kowalska
Bohdan Gorski
Tomasz Huzarski
Tomasz Byrski
Jacek Gronwald
Jowita Huzarska
Barbara Gawronska-Szklarz
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Pomeranian Academy Of Medicine
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Application filed by Pomeranian Academy Of Medicine filed Critical Pomeranian Academy Of Medicine
Priority to CA002535506A priority Critical patent/CA2535506A1/en
Priority to JP2006523155A priority patent/JP2007502270A/ja
Priority to AU2004263070A priority patent/AU2004263070A1/en
Priority to EA200600386A priority patent/EA200600386A1/ru
Priority to EP04775169A priority patent/EP1660060A2/en
Publication of WO2005013951A2 publication Critical patent/WO2005013951A2/en
Publication of WO2005013951A3 publication Critical patent/WO2005013951A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • compositions and methods for the prevention of breast and ovarian cancer FIELD OF THE INVENTION
  • the present invention relates to a composition of selenium (or its salts or derivatives or any other selenium compound) as well as methods for the prevention of breast / ovarian cancer in females with inherited high risk of cancer, particularly in carriers of BRCAl gene mutations.
  • BRCAl US5654155
  • BRCA2 genes are related to high genetic predispositions to cancers.
  • BRCAl and BRCA2 genes have been cloned and, at present, their abnormalities can be detected at DNA and RNA levels. Carriers of mutations within above genes have high risk of breast and / or ovarian cancers.
  • BRCAl is the first gene recognized to be associated with high risk of breast and ovarian cancer (Miki et al, Science, 266-271, 1994).
  • BRCAl gene (GENBANK Accession Numbers: U14680 and 15595) contains 24 exons dispersed within 100 kbp of genomic DNA and its mRNA is of 7.8 kbp of the length. Intensive studies of this gene allowed to identify numerous BRCAl mutations. For example, US5693473 is reporting large registry of such changes. WO 99/29903 is describing the next fifteen BRCAl mutations.
  • BRCA2 gene (GENBANK accession Number U43746) contains 27 exons dispersed within 70 kbp of genomic DNA and its mRNA is of 11-12 kbp of the length.
  • BRCA2 gene Numerous mutations of BRCA2 gene have been reported as associated with cancer predisposition (for example WO 9928506). All of described BRCAl and BRCA2 gene mutations are available on page: http://www.nchgr.nih.gov/dir/lab-transfer/bic. BRCAl and BRCA2 mutations can be located in different exons. Increased frequency of selected particular mutations in families with breast / ovarian cancer aggregation has been recognized in some ethnic groups / populations such as Ashkenazi Jews among whom the high incidence of BRCAl 185delAG and 5382insC and BRCA2 6174delT are well known.
  • an object of the invention to provide pharmaceutical compositions and methodology of their application allowing efficient lowering of the risk of breast / ovarian cancers in individuals with high genetic predisposition to these tumors, especially in carriers of BRCAl gene mutations.
  • Another object of the invention is to provide such pharmaceuticals for chemoprevention of breast / ovarian cancers, which should be offered to females with constitutional mutations of BRCAl gene.
  • the present invention is directed to pharmaceutical composition for lowering the risk of breast / ovarian cancer in person with inherited high risk of disease, especially in carrier of BRCAl mutation, characterized by contents of therapeutically-effective amount of selenium (e.g. in form of its salt or other derivatives thereof or any other known selenium comprising compound) and, if necessary, pharmaceutically acceptable carrier.
  • selenium is selected among its organic forms such as methylselenocysteine, methyloseleninic acid, selenomethinine, selenocysteine or inorganic forms such as selenium dioxide, selenonic acid, selenic acid and their salts.
  • selenium compound is a salt selected among: barium selenite, lithium selenite, calcium selenite and, what is particularly valuable, sodium selenite.
  • pharmaceutical composition is an isotonic solution, containing selenium at concentration 0.1 - 10% w/w. It can be recommended to use as a dissolvent an aqueous solution of ethanol at concentration 10 - 96% w/w., distilled water, physiologic solution preferably buffered. It can be recommended as well if composition according to invention contains selenium salt in aqueous solution of ethanol.
  • the subject of invention is also the method of prevention of breast / ovarian cancer in person with inherited high genetic risk of tumor particularly in female carrier of BRCAl characterized by supplementation of patient with compounds containing selenium (or its salts or derivatives), and using compositions as described above. It can be recommended that in methodology according to invention patient is supplemented with selenium at doses 50 - 1000 ⁇ g per day. It is valuable, in methodology according to invention, to use composition containing selenium after detection in patient the constitutional BRCAl gene mutation. Unexpectedly, increased sensitivity to bleomycin as measured using cytogenetic test according to Hsu was detected in BRCAl mutation carriers (0.58 vs.
  • BRCAl carriers matched for mutation type and year of birth.
  • 1 breast cancer case was observed in the group supplemented with selenium and 4 breast cancers plus 1 ovarian cancer in the control group.
  • occurrence of new breast/ovarian cancers was analysed in the group of 200, initially unaffected, carriers of BRCAl mutations supplemented with ethanol solution of sodium selenite at dose 300 ⁇ g per day and in the control group of 200 BRCAl carriers matched for mutation type and age/average age 38.6 yrs).
  • 1 breast and 1 peritoneal cancers were observed in the group supplemented with selenium, whereas 2 breast and 2 ovarian cancers were diagnosed in the control group.
  • inventions and methodology of their application allowing efficient lowering of the risk of breast / ovarian cancers in individuals with high genetic predisposition to these tumors, especially in carriers of BRCAl gene mutations. Further, the invention provides such pharmaceuticals for chemoprevention of breast / ovarian cancers, which should be offered to females with constitutional mutations of BRCAl gene.
  • invention provides the pharmaceutical composition for lowering the risk of breast / ovarian cancer in person with inherited high risk of disease, especially in carrier of BRCAl mutation, which composition contains selenium (or its salt or derivatives or any other selenium comprising compound) and, if necessary, pharmaceutically acceptable carrier.
  • selenium or its salt or derivatives refers to any known selenium comprising compound.
  • the selenium can be present in elemental form and/or as all other organic or inorganic selenium compounds. In such compounds selenium can have -2, 0, +2, +4, and +6 oxidation states.
  • the body detoxifies the higher oxidation state forms by reducing them to -2 and methylating to form dimethyl selenide. Dimethyl selenide is preferred and it can be used in conjunction with other selenium containing compounds.
  • inorganic selenium compounds such compounds as selenium dioxide, selenonic acid, selenic acid and their salts, especially metal selenides or selenites (e.g. potassium selenide, sodium selenide, sodium selenite, zinc selenide, barium selenite, lithium selenite, calcium selenite and other metal selenides or selenites).
  • metal selenides or selenites e.g. potassium selenide, sodium selenide, sodium selenite, zinc selenide, barium selenite, lithium selenite, calcium selenite and other metal selenides or selenites.
  • selenium can be used in its organic forms such as seleno-amino acid e.g. methylselenocysteine, methyloseleninic acid, selenomethinine, selenocysteine.
  • selenium examples include dimethyl selenide, all other organic selenides, selenoglutathione, and the organo-selenium complex Factor 3. It can be recommended also that selenium originates from such natural products like Se-enriched yeast or broccoli. Selenium occurs naturally in varying amounts in a wide variety of foods and also is present as an impurity in the natural form of the sulfur- containing amino acids, e.g., with methionine as the compound selenomethionine. This latter is due to the fact that the chemical behavior and reactivity of sulfur and selenium are very similar. Thus, in food grade sulfur-containing amino acids, the corresponding seleno-amino acid is normally present and thus contains selenium in significant amounts.
  • Examples of such useful edible sulfur-containing amino acids are: cysteine, methionine, cystine, cystathionine, pencillamine cysteine disulfide, penicillamine, 2-amino-4,4-dimethyl-mercaptobutyric acid, vitamin U, brasinine, djenkolic acid, 2-amino-4-isopropyl-mercaptobutyric acid, 2-amino-4-butyl mercaptobutyric acid, 2-amino-4,4-diethyl-mercaptobutyric acid, dibenzo-yldjenkolic acid, the monohydrochloride of djenkolic acid, the hydrochloride of cysteine, 2-amino-2-ethyl-3- mercapto-propanoic acid, 2-thiolhistidine, thiomalic acid, the hydrochloride of cysteine, homocysteine, pantetheine, panthethine, Coenzyme A, and cysteic acid.
  • the sulfur-containing amino acids, proteins, and peptides are normally used in the hydrochloride form or in weak acid or base salt form because they are more readily water soluble.
  • Examples of useful natural sulfur-containing peptides are: glutathione (a tripeptide of glutamic acid, cystein and glycine, also termed gamma-glutamyl-cysteinyl-glycine), cysteinyl- glycine, and gamma-cysteinyl-methionyl-glycine.
  • Examples of useful sulfur-containing proteins are: keratin, insulin, albumin, ribonuclease, fibroin, collagen and elastin. All of the scleroproteins
  • albuminoids some of which are mentioned above, may be also useful as natural source of selenium.
  • pharmaceutically acceptable carrier refers to term very well know for the person skilled in the art. Methods and pharmaceutical carriers for preparation of pharmaceutical compositions are well known in the art, as set out in textbooks such as Remington's Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pennsylvania, USA. Further information on preferred formulations is also provided in the more detailed description of the invention set out below (see example 1).
  • therapeutically-effective amount means an amount of a selenium comprising compound, as defined above, to yield a desired therapeutic response, i.e.
  • the specific "therapeutically- effective amount” will, obviously, vary with such factors as the physical condition of the subject, the specific formulations employed and the structure of the used "selenium or its salt or derivatives". Particularly, it can be recommended that in methodology according to invention patient is supplemented with selenium at doses 50 - 1000 ⁇ g per day or appropriate dose of selenium comprising compounds which dose includes such amount of selenium.
  • the compound of the invention may be administered in conjunction with one or more other known anti- neoplastic and/or cancer preventive agents.
  • the compound of the invention and the second agent may be administered together or sequentially.
  • selenium can be chosen from organic forms such as methylcysteine, methylseleninic acid, selenomethionine, selenocysteine or from inorganic forms such as selenium dioxide, selenic acid, (H 2 SeO 3 ) or its salts.
  • selenium (IV) salt valuable for preparation of compositions according to invention is sodium selenite. Natural products with high concentration of selenium such as selenium-enriched yeast or broccoli are attractive compounds as well. Particularly valuable, although not the only one, composition according to invention are solutions of selenium at concentration 0.1 - 10% w/w, especially isotonic solutions.
  • Such solutions can be made, for example, using such dissolvents as aqueous solution of ethanol at concentration 10 - 96% w/w, distilled water, physiologic solution especially if buffered. It has been shown that the optimum of pharmacological effect can be achieved if daily dose is 50 - 1000 ⁇ g of selenium.
  • the above values are modifiable depending on biological access of selenium applied to preparation of composition, as well depending on influence of associated compounds, pharmaceutical carriers. Selected, although not the only ones, examples of such compositions are presented below: A) Ethanol solution of sodium selenite.
  • composition - 2.03 g of sodium selenite (Na 2 SeO 3 ) is dissolved in 334.32 g of H 2 O. To aqueous solution of sodium selenite obtained as above 663.65 g of 96% aqueous solution of ethanol is added, and the solution is carefully mixed. Composition prepared in such way can be used for oral supplementation of patient, 2 times 10 drops per day, what corresponds to daily dose around 300 ⁇ g of pure selenium. It can be recommended to divide composition into bottles containing 11-12 g, because such amount covers one-month supplementation. Described composition is stable, maintains its form and activity at least 18 months if stored at 4° C. It can be used by patients without giving side effects.
  • Composition based on aqua can be prepared by replacement of ethanol by distilled water or physiologic solution (preferably buffered) in recipe as in A.
  • Example 2.1ncreased rates of chromosome breakage in BRCAl carriers are reduced by oral selenium supplementation.
  • Study subjects were recruited from among the attendees of a single familial cancer clinic of the Hereditary Cancer Centre of the Pomeranian Academy of Medicine in Szczecin, Poland. Women were referred to this clinic because of a family history of breast or ovarian cancer. The women who participated in this study had previously been offered, and had consented to, genetic testing. Case women were recruited from among those who had been found to be carriers of a deleterious mutation in the BRCAl gene.
  • the most common mutation was the Polish founder mutation 5382 ins C (16 carriers) but there were 10 women with other BRCAl mutations. Control subjects were recruited from among the family members of the carriers (cases), but who had been determined not to carry the deleterious mutation. It was possible to generate 26 case- control pairs. In 20 instances the control was the sister of the case and in six instances she was a more distant relative. Only healthy women were invited to participate in this study; women with a past history of breast, ovary or other form of cancer were excluded. Each woman provided a blood sample at some time during one year study. Chromosome sensitivity to bleomycin was measured according to the method of Hsu et al.
  • Bleomycin (Nippon-Kayuka) was added to the cell culture five hours before the end of the culture at a concentration of 0.03 IU/ml. Conventional harvesting and Giemsa staining were made. For each subject, 100 consecutive euploid cells in metaphase were read (cells with overlapping chromosomes were excluded). Each chromatid aberration (excluding gaps) was scored as one breakpoint and each exchange-type aberration was scored as two breakpoints. The total number of breakpoints per 100 cells was recorded for each subject. Reading of coded slides was performed blindly by one of us.
  • the mean number of breaks per cell was calculated after inspection of 100 cells.
  • the mean level of chromosome breaks was compared in the 26 case-control pairs using the paired t-test.
  • the mean number of chromosome breaks per cell was 0.58 for the BRCAl mutatin carriers (range 0.34 to 0.73) and was 0.39 for the controls (range 0.28 to 0.62) (table 1).
  • the value for the carrier exceeded that for the related control, for two pairs the control value was the higher of the two and for one pair the two values were equal (p ⁇ 0.0001; sign test).
  • the mean difference between the two groups was highly significant (p ⁇ 0.0001).
  • a second group of BRCAl carriers was recruited from this clinic for the purpose of studying the effect of selenium supplementation on frequencies of chromosome breaks. Thirty-five women with BRCAl mutations agreed to participate in this phase of the study. Blood samples were taken prior to the onset of selenium supplementation, and again at a time from one month to three months following the start of daily selenium supplementation. Prior to selenium supplementation, the mean number of induced chromosome breaks per cell was 0.63 (range 0.42 to 0.81). An oral selenium solution was provided to the study subjects which contained 690 ⁇ g of pure selenium, in the form of sodium selenite (Na 2 SeO 3 ) per ml of 70% ethanol.
  • Subjects were requested to consume 0.2 ml of the solution twice daily.
  • a second blood sample was taken at a time from one month to three months after commencement of selenium supplementation and the bleomycin test was repeated.
  • the mean number of chromosome breaks per cell was reduced to 0.40 (range 0.27 to 0.60).
  • the post-supplementation level showed a decline from the baseline level (table 2) and the mean difference was highly significant (p ⁇ 10 "10 ).
  • Example 3 Supplementation of female BRCAl mutation carriers with selenium is reducing significantly the risk of breast / ovarian cancers. Occurrence of breast / ovarian cancers in the group of 30, initially healthy, carriers of BRCAl mutations taking orally ethanol solution of sodium selenite at dose 300 ⁇ g daily and in the control group of 30 BRCAl carriers matched for mutation type and year of birth, was observed during two years. Average age in both groups was 46.5 years. During the period of observation 1 breast cancer case was diagnosed in the group supplemented with selenium and 4 breast cancers plus 1 ovarian cancer have been diagnosed in control group. (Tab. 3).

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PCT/PL2004/000063 2003-08-11 2004-08-10 Pharmaceutical compositions for preventing breast and ovarian cancer WO2005013951A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002535506A CA2535506A1 (en) 2003-08-11 2004-08-10 Pharmaceutical compositions for preventing breast and ovarian cancer
JP2006523155A JP2007502270A (ja) 2003-08-11 2004-08-10 乳癌および卵巣癌の予防のための医薬組成物および方法
AU2004263070A AU2004263070A1 (en) 2003-08-11 2004-08-10 Pharmaceutical compositions for preventing breast and ovarian cancer
EA200600386A EA200600386A1 (ru) 2003-08-11 2004-08-10 Фармацевтические композиции и способы предотвращения рака молочной железы и яичников
EP04775169A EP1660060A2 (en) 2003-08-11 2004-08-10 Pharmaceutical compositions for preventing breast and ovarian cancer

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PLP.361597 2003-08-11
PL361597A PL214402B1 (pl) 2003-08-11 2003-08-11 Zastosowanie selenu albo jego zwiazku do otrzymywania srodka do obnizania odziedziczonego ryzyka zachorowania na raka piersi lub jajnika

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WO2005013951A3 WO2005013951A3 (en) 2005-09-15

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JP (1) JP2007502270A (ja)
KR (1) KR20060066719A (ja)
CN (1) CN1835740A (ja)
AU (1) AU2004263070A1 (ja)
CA (1) CA2535506A1 (ja)
EA (1) EA200600386A1 (ja)
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ZA (1) ZA200602081B (ja)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1796691A1 (en) * 2004-09-21 2007-06-20 Velacor Therapeutics Pty Ltd Inorganic selenium for treatment of cancer
WO2008151520A1 (fr) * 2007-06-13 2008-12-18 University Of Science And Technology Of China Utilisation de sélénosulfate de sodium pour complémenter le sélénium et améliorer l'efficacité de traitement d'agents de chimiothérapie, et son procédé de préparation rapide
WO2009043106A1 (en) * 2007-10-03 2009-04-09 Velacor Therapeutics Pty Ltd Inorganic selenium and angiogenesis
WO2009113888A2 (en) * 2008-03-13 2009-09-17 Pomorska Akademia Medyczna Method for determining reduced predisposition to cancer based on genetic profile
WO2011030108A1 (en) * 2009-09-11 2011-03-17 Isis Innovation Limited Jmjd2 demethylase inhibitors
WO2012067525A1 (en) 2010-11-18 2012-05-24 Pomorski Uniwersytet Medyczny Genotypes and selenium level as a markers of breast/ovarian cancer risk in brca1 mutation carriers
RU2605287C2 (ru) * 2011-04-01 2016-12-20 Иасомай АБ Новая комбинация, содержащая n-ацетил-l-цистеин, и ее применение
EP2968404A4 (en) * 2013-03-15 2017-01-04 Alltech, Inc. Compositions comprising selenium and use of same for the treatment and prevention of disease or conditions associated with mitochondrial dysfunction

Families Citing this family (3)

* Cited by examiner, † Cited by third party
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KR20090127939A (ko) * 2007-03-26 2009-12-14 디코드 제네틱스 이에이치에프 유방암의 위험도 평가, 진단, 예후 및 치료용 마커인 염색체 ２ 및 염색체 １６ 상의 유전적 변이
KR101026291B1 (ko) * 2008-06-30 2011-03-31 주식회사 태강 SeO2 doped W-Mo-Li 화합물을 함유한 항암제 조성물
JP6313479B2 (ja) * 2014-03-14 2018-04-18 オールテック，インク． 有機セレン化合物の組成物およびその使用方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999064018A1 (de) * 1998-06-09 1999-12-16 Biosyn Arzneimittel Gmbh Kombination von selen-haltigen verbindungen mit zytostatika

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999064018A1 (de) * 1998-06-09 1999-12-16 Biosyn Arzneimittel Gmbh Kombination von selen-haltigen verbindungen mit zytostatika

Non-Patent Citations (16)

* Cited by examiner, † Cited by third party
Title
CAFFREY P B ET AL: "SELENITE CYTOTOXICITY IN DRUG RESISTANT AND NONRESISTANT HUMAN OVARIAN TUMOR CELLS" CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 52, no. 17, 1 September 1992 (1992-09-01), pages 4812-4816, XP008041713 ISSN: 0008-5472 *
CAFFREY P B ET AL: "SENSITIVITY OF MELPHALAN-RESISTANT TUMORS TO SELENITE IN VIVO" CANCER LETTERS, NEW YORK, NY, US, vol. 121, no. 2, 1997, pages 177-180, XP008041650 ISSN: 0304-3835 *
DAS, B. ET AL: "Regulation of growth and polyamine metabolism in MCF-7 human breast adenocarcinoma cells by selenium" INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES , 61(4), 213-218 CODEN: IJSIDW; ISSN: 0250-474X, 1999, XP008041662 *
DONG, YAN ET AL: "Identification of molecular targets associated with selenium-induced growth inhibition in human breast cells using cDNA microarrays" CANCER RESEARCH , 62(3), 708-714 CODEN: CNREA8; ISSN: 0008-5472, 2002, XP008041640 *
IP C ET AL: "MAMMARY CANCER PREVENTION BY REGULAR GARLIC AND SELENIUM-ENRICHED GARLIC" NUTRITION AND CANCER, LONDON, GB, vol. 17, no. 3, 1992, pages 279-286, XP002920430 ISSN: 0163-5581 *
IP C ET AL: "SELENIUM-ENRICHED GARLIC INHIBITS THE EARLY STAGE BUT NOT THE LATE STAGE OF MAMMARY CARCINOGENESIS" CARCINOGENESIS, IRL PRESS, LONDON, GB, vol. 17, no. 9, 1996, pages 1979-1982, XP008041663 ISSN: 0143-3334 *
IP, CLEMENT: "Anticarcinogenic effect of selenium in the dimethylbenz(a)anthracene- induced mammary tumor model in rats" JAOCS, J. AM. OIL CHEM. SOC. , 61(12), 1881-7 CODEN: JJASDH, 1984, XP008042181 *
KAECK, MARK ET AL: "Differential induction of growth arrest inducible genes by selenium compounds" BIOCHEMICAL PHARMACOLOGY , 53(7), 921-926 CODEN: BCPCA6; ISSN: 0006-2952, 1997, XP002315942 *
KOWALSKA E ET AL: "Increased rates of chromosome breakage in BRCA1 carriers are reduced by oral selenium supplementation" EJC SUPPLEMENTS, vol. 2, no. 3, March 2004 (2004-03), page 186, XP008041608 & EUROPEAN BREAST CANCER SCREENING GROUP MEETING - BREAST CANCER SCREENING IN EUROPE - CURRENT STATUS; MARCH 16-20, 2004 ISSN: 1359-6349 *
MEDINA, D. ET AL: "Se-methylselenocysteine: A new compound for chemoprevention of breast cancer" NUTRITION AND CANCER , 40(1), 12-17 CODEN: NUCADQ; ISSN: 0163-5581, 2001, XP008041658 *
REDMAN, CLAIRE ET AL: "Inhibitory effect of selenomethionine on the growth of three selected human tumor cell lines" CANCER LETTERS (SHANNON, IRELAND) , 125(1,2), 103-110 CODEN: CALEDQ; ISSN: 0304-3835, 1998, XP008041649 *
RONAI, ZE'EV ET AL: "Effects of organic and inorganic selenium compounds on rat mammary tumor cells" INTERNATIONAL JOURNAL OF CANCER , 63(3), 428-34 CODEN: IJCNAW; ISSN: 0020-7136, 1995, XP008041677 *
SIEJA, KRZYSZTOF: "Selenium (Se) deficiency in women with ovarian cancer undergoing chemotherapy and the influence of supplementation with this micro-element on biochemical parameters" PHARMAZIE , 53(7), 473-476 CODEN: PHARAT; ISSN: 0031-7144, 1998, XP008041722 *
SINHA, R. ET AL: "Effects of methylselenocysteine on PKC activity, cdk2 phosphorylation and gadd gene expression in synchronized mouse mammary epithelial tumor cells" CANCER LETTERS (SHANNON, IRELAND) , 146(2), 135-145 CODEN: CALEDQ; ISSN: 0304-3835, 1999, XP008041646 *
YEO, JUN-KYU ET AL: "Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells" CANCER LETTERS (SHANNON, IRELAND) , 182(1), 83-92 CODEN: CALEDQ; ISSN: 0304-3835, 2002, XP8041642 *
YUAN R ET AL: "Co-ordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells" PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL MEETING, no. 41, March 2000 (2000-03), page 743, XP001182998 & 91ST ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH.; SAN FRANCISCO, CALIFORNIA, USA; APRIL 01-05, 2000 ISSN: 0197-016X *

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