- THERAPEUTIC FOR HEPATIC CANCER
-
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
- -
-
-
- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
- -
-
-
- Synthetic lipid-a-analogs and uses thereof
-
New synthetic Lipid-A analogs based on monosaccharide (1) and disaccharide (2) derivatives were designed and prepared in the present invention. Both structures (1) and (2) incorporate novel lipid structures (3) and (4) that are not found in nature. Also, novel disaccharide Lipid-A structures (2) that incorporate novel contingents of uniform lipids and where R1, R4 and R5 are the same substitution group of structure (III) were synthesized. Liposome formulations containing totally synthetic components such as synthetic Lipid-A and synthetic lipopeptide derived from tumor-associated MUC1 mucin are described along with their therapeutic utility. Comparative test results of immunostimulating properties and toxicity of Lipid-A analogs (1) and (2) are included.
- -
-
-
- Immune Modulating Oligonucleotides in Connection with Chemotherapeutic Measures
-
The invention relates to the use of immune modulators on the basis of DNA in the form of covalently closed nucleic acid molecules comprising immune stimulatory sequence motifs, for the production of a pharmaceutical for the therapeutic treatment of tumor diseases in combination with chemotherapeutic drugs.
- -
-
-
- Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
-
The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (""RT-PCR""). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
- -
-
-
- Toward the design of an RNA:DNA hybrid binding agent
-
One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA:DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.
- Chu, Wenhua,Kamitori, Shigehiro,Shinomiya, Miho,Carlson, Robert G.,Takusagawa, Fusao
-
p. 2243 - 2253
(2007/10/02)
-
- Synthesis and Properties of Some Peptide Analogues of Actinomycin D
-
Analogues of actinomycin D (AMD) were synthesized in which amino acid replacements were made at various sites in the peptide moieties.These include (i) replacement of both N-methylvalines by N-methylleucine, (ii) replacement of both sarcosines by N-glycine, and (III) replacement of one or both D-valines by D-threonine.The purpose of replacements ii and iii was to ascertain the effect upon biological activity of introducing a new side chain which could be functionalized to allow the attachment of carrier molecules such as antibodies.NMR data indicated that none of the analogues had solution conformations significantly different from that of AMD.Difference spectra with DNA revealed that replacement i enhanced binding while the other analogues bound less strongly to DNA.All the analogues had lower antimicrobial activities than AMD.In contrast, 5,5'-(MeLeu)2AMD displayed in vitro antitumor activity comparable with that of AMD at approximately 100-fold lower concentrations.
- Mauger, Anthony B.,Stuart, Oswald A.,Katz, Edward
-
p. 1297 - 1301
(2007/10/02)
-
- Amino acid and hydroxyamino acid transporter compounds for therapeutic applications, process and use
-
Amino acid and hydroxyamino acid transporter compounds are provided, in which an amino acid or hydroxyamino acid as a carrier is linked via an ester linkage to a therapeutic compound, and having one of the general formulae: in which AA represents the amino acid or hydroxyamino acid, HAA represents the hydroxyamino acid, and Z1 and Z2 represent a therapeutic compound, or a linking compound attached to COOH or OH of the hydroxyamino acid and to the therapeutic compound, as well as a process for preparing the same, and a process for administration of the same to animals, to obtain the benefit of the therapeutic effect of the therapeutic compound.
- -
-
-
- Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
-
A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
- -
-
-
- Conformation and Dimerization of Actinomycin-Related Peptide Lactones in Solution and in the Solid State
-
Actinomycin-related peptide lactone derivatives with the amino acid sequences Thr-D-Val-Pro-Sar-MeVal and Thr-D-Val-Pro-Sar-MeAla and the corresponding actinomycins (actinomycin D and its novel 5,5'-MeAla analoque) were synthesized by a new route.The solution properties of these compounds were studied by proton NMR in chloroform and acetone solutions.In dry chloroform, two conformers, A and C, are found, the ratio of which was concentration-dependent and results from dimerization of the A conformer.An X-ray crystallographic investigation of a Thr-D-Val-Pro-Sar-MeAla derivative indicated that hydrogen-bond associated pairs of A conformers, with a juxtapositional geometry remarkably similar to that known for actinomycin, were present in the solid state.
- Mauger, Anthony B.,Stuart, Oswald A.,Ferretti, James A.,Silverton, James V.
-
p. 7154 - 7163
(2007/10/02)
-