Unlock instant, AI-driven research and patent intelligence for your innovation.

Gemcitabine combination therapy

Inactive Publication Date: 2012-11-29
CELGENE CORP
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The combination therapy demonstrates significant utility in treating proliferative disorders and Ras-expressing tumors, showing tumor growth inhibition and potential synergistic effects, particularly in pancreatic cancer models, offering a more effective approach than standard therapies.

Problems solved by technology

Dysregulation or loss of control of cell division can result in the development of any of a variety of cell proliferative disorders, many of which are debilitating or deadly.
Furthermore, many of the most deadly cancers involve Ras-expressing tumors.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Gemcitabine combination therapy
  • Gemcitabine combination therapy
  • Gemcitabine combination therapy

Examples

Experimental program
Comparison scheme
Effect test

example 1

Depsipeptide (FK228) Alone and in Combination with Gemcitabine in In Vivo Mouse Xenograft Model of Ras-Expressing Pancreatic Tumor

[0150]The present Example demonstrates that both depsipeptide (FK228; FR901228; romidepsin) and gemcitabine can effectively inhibit tumor growth in a mouse xenograft model, and further demonstrates a surprising synergistic effect of the combination.

[0151]Panc-1, obtained from the ATCC, is a pancreas tumor cell line (oncogenic K-ras) originating from a 56 year old Caucasian male. In this study, female nude mice were implanted subcutaneously (SC) by trocar with Panc-1 tumor fragments harvested from SC growing tumors in nude mice hosts. When tumors reaches approximately 140 mm3, animals were pair matched by tumor size into treatment and control groups (N=9 mice per group) (FIG. 4). The day of treatment initiation was specified as Day 1. Vehicle control and FK228 were administered intravenously on a Q4D×3 schedule (Days 1, 5, and 9). Gemcitabine was administe...

example 2

Combination of FK228 and Gemcitabine is More Effective than Either Agent Alone in a Ras-Transformed Pancreatic Adenocarcinoma Model

[0155]The present Example demonstrates that the combination of FK228 and gemcitabine is more effective than either agent alone in a pancreatic adenocarcinoma model.

[0156]Abstract:

[0157]To examine activity and mechanism of FK228, antitumor efficacy was tested in PANC-1 pancreatic adenocarcinoma model representing transformed Ras, either as a single agent or in combination with gemcitabine. Following PANC-1 study completion, tumor and sera were obtained from:[0158]the vehicle control;[0159]FK228 dosed at 5 mg / kg once every four days for three treatments (Q4D×3);

[0160]Gemcitabine at 80 mg / kg (Q3D×4); and[0161]the drug combination.

Expression of c-Myc, acetylated histones 3 and 4, and p21waf1 was compared between control and FK228 groups by immunoblotting and was quantified following actin normalization. Serum levels of putative tumor products b-FGF and MMP-2...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides compositions and methods for the treatment of cell proliferative disorders using at least one DAC inhibitor and gemcitabine.

Description

BACKGROUND OF THE INVENTION[0001]Dysregulation or loss of control of cell division can result in the development of any of a variety of cell proliferative disorders, many of which are debilitating or deadly. Although much has been learned about mechanisms involved in cell proliferation, and therefore about common biological principles underlying a variety of different disorders, there remains a need for the development of new and / or improved therapies for the treatment of such conditions.[0002]There is a particular need for the development of improved therapies for the treatment of tumors that express the Ras oncogene. Ras-expressing tumors are often more resistant to standard therapies. Furthermore, many of the most deadly cancers involve Ras-expressing tumors. For example, 90-95% of pancreatic tumors are Ras-expressing. Similarly, 40-45% of colorectal tumors, 40% of bladder tumors, 15-20% of non small cell lung carcinomas express Ras. Indeed, 10-25% of myelodysplastic syndromes (M...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/7068A61P35/00
CPCA61K31/7068A61K38/15A61K45/06A61K38/12A61K2300/00A61P35/00
Inventor MCCULLOCH, WILLIAMKEEGAN, MITCHELL
Owner CELGENE CORP