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WO1997010842A1 - COMBINAISON A BASE D'INTERFERON β POUR LE TRAITEMENT DU CANCER DE LA PROSTATE - Google Patents

COMBINAISON A BASE D'INTERFERON β POUR LE TRAITEMENT DU CANCER DE LA PROSTATE Download PDF

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Publication number
WO1997010842A1
WO1997010842A1 PCT/EP1996/004079 EP9604079W WO9710842A1 WO 1997010842 A1 WO1997010842 A1 WO 1997010842A1 EP 9604079 W EP9604079 W EP 9604079W WO 9710842 A1 WO9710842 A1 WO 9710842A1
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WO
WIPO (PCT)
Prior art keywords
interferon
gicnac
value
patient
psa
Prior art date
Application number
PCT/EP1996/004079
Other languages
German (de)
English (en)
Inventor
Torsten Strohmeyer
Original Assignee
Schering Aktiengesellschaft
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE1995136593 external-priority patent/DE19536593A1/de
Priority claimed from DE1995136818 external-priority patent/DE19536818A1/de
Application filed by Schering Aktiengesellschaft filed Critical Schering Aktiengesellschaft
Priority to AU71306/96A priority Critical patent/AU7130696A/en
Publication of WO1997010842A1 publication Critical patent/WO1997010842A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/215—IFN-beta

Definitions

  • the present invention relates to the use of an interferon- ⁇ for the manufacture of a medicament for the treatment of prostate cancer.
  • the invention is based on the priority-based applications DE 195 36 593.3 (filing date September 19, 1995) and DE 195 36 818.5 (filing date September 21, 1995), which were filed with the German Patent Office in Germany.
  • Prostate carcinoma is a malignant, metastatic, inoperable carcinoma. Prostate cancer is only occasionally and partially androgen dependent.
  • a largely prostate cancer-specific tumor marker is the prostate-specific antigen (PSA), which demonstrably increases in the serum as the tumor progresses.
  • PSA prostate-specific antigen
  • This PSA value is described in the literature in S. BARNETT et al. (1993) Annais of Internal Medicine, Vol 119, No. 9. (Nov. 1, 1993) pp 914 and J.E. OESTERLING (1991) J. Ural. Vol. 145: pp 907-927. It is the only tumor-associated marker in prostate cancer that is reliably detectable, occurs in almost all prostate cancer patients and correlates with the stage of the disease. The PSA marker has been known in the clinic since 1980. His relation to tumor progression has always been conscious. (B.C. KRAMER et al. (1993) Annais of Internal Medicine Vol. 119, 914 in conjunction with L.D. PAPSIDERO et al. (1980) Cancer Res. Vol. 40: 2428-2432)
  • interferons The nomenclature used in Nature, Vol. 286, p 2421 (1980) for the group of interferons should be used. Two classes of interferons are known. Class I interferons are small, acid-stable glycoproteins that
  • interferon- ⁇ makes cells resistant to viral infections.
  • the class II interferons are acid labile.
  • Three groups of interferons are known: interferon- ⁇ , interferon-ß and interferon- ⁇ .
  • Interferon-ß shows biological activity in glycosylated or unglycolysed form. (W.E. STEWART et al. (1979) Virology Vol. 97: 473-476). Interferon-ß is usually not detectable in normal or healthy cells. Only when these cells are exposed to interferon-ß inducers is the interferon-ß expressed. Viruses are usually good interferon- ⁇ inducers, but non-viral inducers are also known (S. BARON and F. DIANZANI (eds.) (1977) Texas Reports on Biology and Medicine, 35: (“Texas Report”), pp 526-540.
  • interferon-ß derivatives which are distinguished by the exchange of amino acids.
  • a recombinant interferon- ⁇ is described in European patent application EP 0 218 825, which has a serine in position 17 instead of a cysteine. This modification also has biological activity.
  • a further, modified, human interferon- ⁇ which has a deletion in position 1, a substitution in position 17 by serine and a non-existing glycosylation. This substance is also biologically active.
  • interferon-ß has not shown any remarkable effect in the treatment of prostate cancer.
  • the object is achieved by the use of at least one interferon- ⁇ for the manufacture of a medicament for the treatment of a patient with prostate cancer, the patient having a PSA value (prostate-specific antigen value) which is opposite the normal PSA level is increased.
  • PSA value prostate-specific antigen value
  • the normal PSA value can be determined relatively and individually by a patient or by an average value which is defined as non-pathological or pathological.
  • a PSA value which is pathologically increased is preferred. It is more preferred to measure a PSA value relatively in the same patient. It is not the increase compared to the average of the population that is decisive, but rather the increase in the individual PSA value in a patient.
  • the tumor can only be effectively treated if the patient is being treated primarily at a time when the PSA value is relatively increasing.
  • the PSA value is increased compared to the normal value or base value. Treatment is preferably carried out at a point in time at which the PSA value shows a change in the increase.
  • the first increase in the PSA value compared to the normal value or base value is the preferred time at the start of the therapy according to the invention.
  • IFN- ⁇ for prostate cancer treatment in patients whose testosterone production has previously been reduced by castration or by drug treatment. After a previously successful anti-hormonal prostate cancer treatment, such patients show a progression of the tumor disease after about two to three years.
  • the PSA value of such patients is good monitor Tumor progress in patients who are closely monitored is usually manifested by an increase in PSA
  • the invention further comprises an interferon- ⁇ , which is the human interferon- ⁇ or a derivative thereof
  • interferon-ß encompasses both the sequence and the glycosylation of human interferon-ß and Interferon- ⁇ -Derivatives All the modifications which lead to a change in the amino acid sequence are included in the derivatives, provided that these modifications include the substitutions, the deletions and / or the insertions of up to 15 amino acids. Deletions, substitutions and / or are preferred Insertions of up to 10 amino acids, more preferably of up to 6 amino acids, most preferably the deletions, substitutions and / or insertions of one, two, three, four or five amino acids
  • an interferon-ß which is a derivative of human interferon-ß and wherein the derivative a) comprises all modifications of the human interferon, which modifications lead to a change in the amino acid sequence, at least one, at most 15 Amino acids are substituted, deleted or inserted without significantly influencing the activity of the modified interferon-ß compared to the test interferon-ß and b) includes all post-translational modifications that do not significantly affect the activity of the active modified interferon-ß compared to the Affect test interferon-ß
  • interferon- ⁇ in which at most 10 amino acids are substituted, deleted or inserted, without the To significantly influence the activity of the modified interferon-ß compared to the test interferon-ß
  • interferon-ß in which at most 6 amino acids are substituted, deleted or inserted is very preferred without significantly influencing the activity of the modified interferon-ß compared to the test interferon-ß
  • interferon-ß in which one, two, three, four or five amino acids are substituted, deleted or inserted, without the activity of the modified interferon-ß compared to the test interferon-ß significantly influence
  • test interferon-ß is an interferon-ß which is unglycosylated, has a substitution in position 17 with senn and a deletion in position 1. This interferon defines the test interferon-ß.
  • a test method is described in T TANIGUCHI et al (1980) Vol 77: 5230-5233 and in DF MARK et al (1984) Vol 81: 5662-5666
  • Amino acids as shown in Table 1, can be substituted without significantly influencing the function of the protein.
  • the activity test must be used to decide what influence the change has on the function of the protein
  • the mutations are defined by the homology (similartty) of two proteins to be compared.
  • the proteins according to the invention have amino acid sequences which have homology of at least 80%, preferably 90%, more preferably 95% and most preferably 98% of the structures according to the invention as defined by the sequence of the recombinant modified interferon- ⁇ with Ser 17 (test-interferon- ⁇ ) Table 1
  • Glycosylation is an essential function of the endoplasmic reticulum and / or the Golgi apparatus.
  • the sequences and branches of the oligosaccharides are formed in the endoplasmic reticulum and modified in the Golgi apparatus. or O-linked oligosacchands (Senn, threonine or hydroxylysine linked)
  • the form of the glycosylation is dependent on the producing cell type and on the type of the corresponding cell type comes from.
  • the extent and type of glycosylation can be influenced by substances, as described in the European publication EP 0 222 313. Varying glycosylation can alter the function of the protein.
  • Proteins often form covalent bonds within the chains. These disulfide bridges are made between two cysteines. The protein is folded specifically. The disulfide bridges stabilize the three-dimensional structure of the proteins.
  • amino acids can be changed as described in the international publication WO 91/10684.
  • the protein can also be sulfated. This change is described in the context of hirudin.
  • the invention further preferably comprises the use of an interferon- ⁇ which has a proportion of biantennary oligosaccharide structures of at least 60%, a proportion of triantennary oligosaccharide structures of at least 15% and a proportion of tetraantennary oligosaccharide structures 0% to 5% and a sialic acid content of at least 80%.
  • an interferon- ⁇ which is glycosylated, a proportion of biantennary oligosaccharide structures of at least 60%, a proportion of triatric oligosaccharide structures of at least 15% and a proportion of tetraantennary oligosaccharide structures ren from 0% to 5% and a sialic acid content of at least 80%.
  • the invention comprises the use of an interferon- ⁇ which has a proportion of biantennary oligosaccharide structures of at least 60%, more preferably 70% and most preferably at least 75%.
  • the invention also comprises the use of an interferon- ⁇ which comprises a proportion of triantennary oligosaccharide structures of at least 15%, preferably 20% and most preferably at least 25%.
  • Interferon- ⁇ is advantageous, the antenna structures having at least one N-acetyllactosamine repeat.
  • the antennae structures can be linked 1-4 and / or 1-6.
  • the tetraantennar portion can be 0.5% to 3%.
  • the invention further comprises the use of an interferon- ⁇ which has a sialic acid content of at least 80%, preferably 85% and most preferably more than 90%.
  • the sialic acid component can be composed of N-acetylneuraminic acid and N-glycolylneuraminic acid.
  • the N-acetylneuraminic acid can take up 90-100% and the N-glycolylneuraminic acid 0-10% of the total sialic acid content.
  • the invention further comprises the use of an interferon- ⁇ which has a proportion of fucose content of at least 85%, preferably 90% and most preferably greater than 95%.
  • the invention further comprises the use of an interferon- ⁇ which has at least one oligosaccharide structure with one or more of the following
  • Gal ß (1-4) GIcNAc ß (1-6) (ix)
  • Gal ß (1-4) GIcNAc ß (1-2) Man ⁇ 1 ⁇ (1-6) Fuc (x)
  • Gal ß (1-4)
  • GIcNAc ß (1-6)
  • NeuAc can also represent N-glycolylneuraminic acid.
  • PSA value prostate-specific - Antigen
  • interferon-ß alone and the combination of interferon-ß and a compound with an antiandrogenic effect also makes sense in patients who have been treated previously or simultaneously with respect to prostate cancer.
  • Such treatment can consist of surgical castration and / or chemical castration, which may be accompanied by antiandrogen treatment.
  • antiandrogen and interferon - ß Use of antiandrogen and interferon - ß; surgical castration and use of antiandrogen and IFN - ß; and chemical castration and the use of antiandrogen and IFN - ß.
  • Antiandrogenic compounds Use of antiandrogen and interferon - ß; surgical castration and use of antiandrogen and IFN - ß; and chemical castration and the use of antiandrogen and IFN - ß.
  • All compounds which act as competitive antiandrogens ie. H. those that mediate their anti-drug effects through strong affinity for the androgen receptor.
  • These anti-androgenic compounds can be both steroidal in origin and non-steroids.
  • the invention comprises the use of a combination according to the invention, the compounds having androgenic activity having the structures of the formula 1 or formula 2:
  • R 1 and R2 each represent a hydrogen atom or both together
  • R 3 represents the acyl radical of an acid customary in steroid chemistry
  • R 4 is hydrogen, acyl or alkyl
  • X-i represents a hydrogen or chlorine atom
  • * 2 represents a hydrogen, fluorine or chlorine atom
  • R5 and R6 each represent hydrogen or both together represent a methylene group
  • X2 represents hydrogen, fluorine or chlorine
  • R 3 represents the acyl radical of an acid customary in steroid chemistry.
  • the methyl group of AB points behind the drawing level in the left formula (eight lines before) and in front of the drawing level in the right formula
  • acyl radical should be understood to mean the radicals of the acids customary in steroid chemistry for the esterification of secondary and tertiary hydroxyl groups.
  • Preferred are aliphatic carboxylic acids with 1-8 carbon atoms, such as, for example, acetic acid, propionic acid, butteric acid, valenic acid, isovalenic acid, capronic acid, onanthic acid, etc.
  • the esters of acetic acid are particularly preferred
  • Alkyl is to be understood as meaning lower alkyl groups with 1-5 carbon atoms, the methyl group being preferred
  • the invention comprises the use of a combination, the compounds with antiandrogenic activity belonging to the group of the following substances
  • Typical compounds of the general formula II are for example
  • 6-chloro-17 ⁇ -acetoxy-17ß-methyl-1 ⁇ , 2 ⁇ -methylene-D-homo-4,6-androstad ⁇ en-3, 17a-d ⁇ on The steroid pyrazoles and triazoles described in patent applications EP-A-0 207 375 and WO-A-92/00992 are also suitable, for example the (5 ⁇ , 17 ⁇ ) -1 '- (methylsulfonyl) -I ⁇ -pregn-20 -yno- (3,2-c) -pyrazol-17-ol;
  • IFN-ß Use of IFN-ß or the combination of IFN-ß and a compound with an antiandrogenic effect
  • the invention includes the use of an interferon-ß alone or the combination of IFN-ß and a compound with antiandrogenic activity, which comprises the pharmacological auxiliary substances and carriers which are physiologically compatible.
  • Interferon-ß or the combination of IFN-ß and a compound with antiandrogenic activity substance
  • the invention further comprises the use of a substance, the patient having a PSA value (prostate-specific antigen value) which is at least 10%, preferably at least 20%, more preferably at least 30, compared to the normal PSA value % is increased.
  • PSA value prote-specific antigen value
  • the PSA value is subject to fluctuations that are determined by the lifestyle and the daily rhythm. Both physical and psychological reasons can cause a fluctuation around an average and within a fluctuation range.
  • the invention comprises the use of a substance, the PSA value being diagnosable extracorporeally.
  • the use of a substance is more preferred, the PSA value being diagnosable in a blood sample.
  • the invention further provides
  • a method for the treatment of prostate carcinoma comprising the administration of an amount of substance according to the invention, the amount suppressing the disease, and the amount of substance being given to a patient in need of such a medication and having a PSA value which is higher than the patient's normal PSA;
  • a pharmaceutical composition for the treatment of prostate cancer which treatment comprises a substance according to the invention and at least one pharmaceutically acceptable carrier and additive, the patient having a PSA value which is higher than the patient's normal PSA value.
  • the suitable dose for this therapeutic effect is different and depends, for example, on the interferon- ⁇ , the host, the type of administration and the type and severity of the conditions to be treated.
  • Values of 10 5 to 4 x 10 7 units (interferon- ⁇ ) per 48 hours are preferred, more preferably 8 x 10 5 to 2 x 10 7 units (interferon- ⁇ ) per 48 hours and most preferably 3 x 10 6 to 8 x 10 6 units (interferon-ß) per 48 hours.
  • the active ingredients can be processed with the additives and / or carrier substances customary in galenical pharmacy according to methods known per se to form the usual forms of administration.
  • Ohmic solutions such as, for example, sesamol or castor oil solutions, are suitable for parenteral administration.
  • solution mediators such as, for example, benzyl benzoate or benzyl alcohol, can be added
  • interferon- ⁇ can be administered in any customary way, in particular injection solutions or suspensions are the corresponding forms for the administration
  • modified interferon- ⁇ according to EP 0 529 300 is the particularly preferred combination. It is administered, for example, in the case of larger mammals, for example humans, in the manner described above.
  • the subcutaneous injection in conventional aqueous solvents, for example physiological saline solution, is for the preferred form of administration for systemic treatment
  • Values of 10 5 to 4 ⁇ 10 7 units (interferon- ⁇ ) per 48 hours and 50 to 500 mg (antiandrogen) per day are preferred, more preferably 8 ⁇ 10 5 to 2 ⁇ 10 7 units (interferon- ⁇ ) per 48 Hours and 50 to 500 mg (antiandrogen) per day and most preferably 3 x 10 6 to 8 x 10 6 units (interferon-ß) per 48 hours and 50 to 500 mg (antiandrogen) per day
  • the combination can be administered simultaneously or at different times
  • the active ingredients can be processed with the additives, carrier substances and / or flavoring agents customary in galenical pharmacy according to methods known per se to form the usual forms of administration
  • Tablets, coated tablets, capsules, pills, suspensions or solutions are particularly suitable for oral administration
  • oily solutions such as e.g. B. sesame oil or castor oil solutions, suitable.
  • solubilizers such as. As benzyl benzoate or benzyl alcohol can be added.
  • the combination can be administered in any conventional way, preferably orally.
  • Suppositories, tablets, capsules, drops, solutions for injection or suspensions are the appropriate forms for administration.
  • the combination can be administered in any conventional way in the case of systemic treatment, in particular injection solutions or suspensions to be injected subcutaneously are the corresponding forms for the administration.
  • modified interferon- ⁇ according to EP 0 529 300 and the antiandrogen cyproterone acetate is the particularly preferred combination. It is used, for example, in larger mammals, e.g. B. humans, administered in the manner shown above.
  • the infusion solution as a continuous infusion in conventional aqueous solvents, e.g. B. physiological saline, is the preferred form of administration for systemic treatment.
  • Patients are selected who have asymptomatic, progressive prostate cancer that can no longer be controlled by hormones alone. Furthermore, the patients show an increase in the PSA concentration, which is determined by blood tests.
  • IFN-ß is used as the drug, which is IFN-ß 1a and a
  • the injections contain 0 ⁇ g, 5 ⁇ g, 15 ⁇ g or 30 ⁇ g interferon-ß 1a, which corresponds to 0 MU, 1 MU, 3 MU or 6 MU (mega-units).
  • the formulation is taken up in 1 ml of distilled water.
  • the interferon-ß is injected subcutaneously three times a week in three dose groups of 1, 3 and 6 MU (mega units).
  • a placebo serves as control, in which only the interferon - ß 1a is missing.
  • composition of an antiandrogenic tablet for oral administration is a composition of an antiandrogenic tablet for oral administration
  • the tablet is manufactured in the usual way on a tablet press. If appropriate, the active compounds according to the invention, each with half of the additives indicated above, can also be pressed separately into a two-layer tablet.
  • composition of another antiandrogenic tablet for oral administration is provided.
  • the tablet is manufactured in the usual way on a tablet press. If appropriate, the active compounds according to the invention, each with half of the additives indicated above, can also be pressed separately into a two-layer tablet.
  • cyproterone acetate For the injection of cyproterone acetate, an oily solution is made by mixing 50 mg of cyproterone acetate with 353 mg of castor oil and 618 mg of benzyl benzoate. This results in 1071 mg, which take up the volume of one milliliter.
  • composition of an interferon-ß injection cf. (i). (ii).
  • the PSA value is determined according to (i). (Iii). measured.
  • test substance cyproterone acetate is dissolved in benzyl benzoate + castor oil (compare approach 3) and the single dose of 50 mg per day s.c. or p.o. applied.
  • test substance is suspended in a carrier liquid (85 mg myrj in 100 ml 0.9% w / v NaCl solution) and the daily dose is administered.
  • carrier liquid 85 mg myrj in 100 ml 0.9% w / v NaCl solution
  • the test substance interferon-ß is in the form of (i). (Ii). sprayed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne l'utilisation d'un interféron β. Ledit interféron β convient à la production de médicaments destinés au traitement du cancer de la prostate. L'interféron β est administré à des patients dont la valeur d'antigène prostatique spécifique (PSA) a augmenté par rapport aux valeurs d'antigène prostatique spécifique précédentes.
PCT/EP1996/004079 1995-09-19 1996-09-17 COMBINAISON A BASE D'INTERFERON β POUR LE TRAITEMENT DU CANCER DE LA PROSTATE WO1997010842A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU71306/96A AU7130696A (en) 1995-09-19 1996-09-17 Combination of beta-interferon for the treatment of prostate cancer

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19536593.5 1995-09-19
DE1995136593 DE19536593A1 (de) 1995-09-19 1995-09-19 Verwendung von einem Interferon-ß zur Behandlung von Prostatakarzinom
DE1995136818 DE19536818A1 (de) 1995-09-20 1995-09-20 Kombination aus Interferon-beta und aus einer antiandrogenen Verbindung zur Behandlung von Prostatakarzinom
DE19536818.5 1995-09-21

Publications (1)

Publication Number Publication Date
WO1997010842A1 true WO1997010842A1 (fr) 1997-03-27

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AU (1) AU7130696A (fr)
WO (1) WO1997010842A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001034176A1 (fr) * 1999-10-28 2001-05-17 Immunolytics Inc. Methode et composition de traitement du cancer de la prostate
WO2001017479A3 (fr) * 1999-09-09 2001-09-20 Androsolutions Inc Methodes et compositions pour prevenir et traiter les troubles de la prostate
US6642274B1 (en) 1999-09-09 2003-11-04 Gary W. Neal Methods and compositions for preventing and treating prostate disorders
RU2328285C2 (ru) * 2006-07-31 2008-07-10 Ефаг АО Средства и способ лечения состояний, при которых терапевтически благоприятным является снижение действия андрогенов, и способ усиления чувствительности андрогензависимых тканей, с применением 9-оксоакридин-10-уксусной кислоты

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992012430A1 (fr) * 1991-01-14 1992-07-23 Endorecherche Inc. Predepistage du cancer de la prostate grace a un antigene specifique de la prostate present dans le serum
EP0529300A1 (fr) * 1991-08-27 1993-03-03 Dr. Rentschler Biotechnologie GmbH Nouvel interféron-bêta humain, procédé de préparation et compositions pharmaceutiques le contenants

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992012430A1 (fr) * 1991-01-14 1992-07-23 Endorecherche Inc. Predepistage du cancer de la prostate grace a un antigene specifique de la prostate present dans le serum
EP0529300A1 (fr) * 1991-08-27 1993-03-03 Dr. Rentschler Biotechnologie GmbH Nouvel interféron-bêta humain, procédé de préparation et compositions pharmaceutiques le contenants

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Title
B.S. KRAMER ET AL.: "PROSTATE CANCER SCREENING: WHAT WE KNOW AND WHAT WE NEED TO KNOW.", ANNALS OF INTERNAL MEDICINE, vol. 119, no. 9, 1 November 1993 (1993-11-01), PHILADELPHIA, PA, US, pages 914 - 923, XP000615585 *
D. GOLDSTEIN ET AL.: "EFFECTS OF INTERFERON BETA SER AND TRANSFORMING GROWTH FACTOR BETA ON PROSTATIC CELL LINES.", THE JOURNAL OF UROLOGY, vol. 146, no. 4, October 1991 (1991-10-01), BALTIMORE, US, pages 1173 - 1177, XP000615633 *
G. SICA ET AL.: "ANDROGEN RECEPTORS AND HORMONE SENSITIVITY OF A HUMAN PROSTATIC CANCER CELL LINE (PC-3) ARE MODULATED BY NATURAL BETA-INTERFERON.", UROLOGICAL RESEARCH, vol. 22, no. 1, 1994, BERLIN, DE, pages 33 - 38, XP000615525 *
M.A. BULBUL ET AL.: "INTERFERON-BETA TREATMENT OF METASTATIC PROSTATE CANCER.", JOURNAL OF SURGICAL ONCOLOGY, vol. 33, no. 4, December 1986 (1986-12-01), NEW YORK, N.Y., US, pages 231 - 233, XP000615606 *
Y. NAKAJIMA ET AL.: "EFFECTS OF INTERFERON-BETA ON GROWTH OF HUMAN PROSTATIC JCA-1 CELLS.", FASEB JOURNAL FOR EXPERIMENTAL BIOLOGY, vol. 7, no. 4, 23 February 1993 (1993-02-23), BETHESDA, MD US, pages A618, XP002022419 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001017479A3 (fr) * 1999-09-09 2001-09-20 Androsolutions Inc Methodes et compositions pour prevenir et traiter les troubles de la prostate
US6642274B1 (en) 1999-09-09 2003-11-04 Gary W. Neal Methods and compositions for preventing and treating prostate disorders
WO2001034176A1 (fr) * 1999-10-28 2001-05-17 Immunolytics Inc. Methode et composition de traitement du cancer de la prostate
US6428785B1 (en) 1999-10-28 2002-08-06 Immunolytics Inc. Method and composition for treating prostate cancer
US6913744B2 (en) 1999-10-28 2005-07-05 Immunolytics Inc. Method and composition for treating prostate cancer
RU2328285C2 (ru) * 2006-07-31 2008-07-10 Ефаг АО Средства и способ лечения состояний, при которых терапевтически благоприятным является снижение действия андрогенов, и способ усиления чувствительности андрогензависимых тканей, с применением 9-оксоакридин-10-уксусной кислоты

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