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Treatment of prostate cancer

a prostate cancer and active ingredient technology, applied in the field of prostate cancer treatment, can solve the problems of severe pain, resistance to treatment, and significant morbidity and death directly from the prostate cancer, and achieve the effects of reducing the risk of prostate cancer, and improving the survival ra

Inactive Publication Date: 2003-09-11
PEPLIN RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

0164] The ability of E. peplus sap to kill prostate cancer cells selectively was assessed by comparing the effect of the sap on prostate cancer cell lines and on normal fibroblasts. Three prostate cancer cell lines were used; PC-3 and DU145 are hormone resistant prostate cancer cell lines and LNcap is a hormone-sensitive prostate cancer cell line.
0165] The prostate cancer cell lines or normal fibroblasts were suspended to a concentration of 5 X 10.sup.3 cells/well in RPMI1640 tissue cultmue medium containing 10% w/v FCS, volume 0.1 ml in microtitre plates.
0166] The cells were incubated for 6 hr at 37.degree. C., foll

Problems solved by technology

As the most common internal cancer in older men and the seventh most common cause of death in men of all ages in developed countR.sub.1es, cancer of the prostate is a seR.sub.1ous health problem in terms of drawn-out personal suffeR.sub.1ng and premature death not to mention the cost to the health care system.
Although many men with cancer of the prostate die from other causes, the high incidence results in significant morbidity and death directly from the prostatic tumor.
Currently-available therapy carR.sub.1es a significant R.sub.1sk of major side effects, including incontinence and impotence, and consequently many men are reluctant to accept treatment at an early stage of the disease.
They cause severe pain, prolonged hospitalization, pathological fractures, spinal-cord compression and paraplegia, and may be fatal.
However, it can only be used once for a given bony secondary.
Parenteral strontium isotopes have had limited success for treatment but their use is limited by their toxicity to the bone narrow, especially platelets.
Bisphosphonates (osteoclast inhibitors) may decrease the bone pain in a few cases, but again are generally disappointing and do not increase life expectancy.

Method used

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example 1

Materials and Methods

[0156] Cells were cultured in RPMI1640 mediurn-10% w / v FCS in 5% v / v CO.sub.2 and 5% v / v oxygen. The latter reproduces physiological conditions and is considered useful in assessing the molecular responses of normal and tumor cells to drugs. Inhibition of cell growth was determined 5-7 days after drug treatment by assay of cell numbers with sulforhodamine B (SRB) in microtitre plates.

[0157] General cell signalling activity of the E. peplus compounds is quantitated by a sensitive assay which the present inventors have developed, in which cells are simultaneously treated with the drug and infected with a non-relicating adenovirus containing the CMV promoter, which drives expression of .beta.-galactosidase (in place of Ela). Approximately 24 hours later, the .beta.-galactosidase activity is measured in an ELISA reader. The sensitivity of this assay (<ng / ml TPA) is sufficient to measure bioactivity in blood and organs and serves as the basis for comparison of struct...

example 2

Pre-treatment of Human Tumor Cells in Culture with Diterpene Esters Potentiates Selective Killing by Untreated Leuktocytes

[0161] The question of whether drug treatment of the target tumor cells causes them to become susceptible to effector cells of the immune system was addressed as follows.

[0162] Leukocytes obtained by lysis of human peripheral blood were added to 5000 MM96L human melanoma cells or 7000 neonatal foreskin fibroblasts per microtitre well at effector: target ratios of 1000, 100 and 10:1. The target cells had been treated with 60 ng / mL PEP008 for 20 hr beforehand, and washed and the medium replaced before the leukocytes were added. After 48 hr incubation with the leukocytes the cultures were washed and labelled with [3H]-thymidine for 2 hr. At 100:1 ratio of effector:target cells, the melanoma cells showed 12% survival with PEP008 whereas the normal fibroblasts had 100% survival. Untreated leukocytes had no effect on cell survival.

[0163] This result showed that the dru...

example 3

Effect of E. peplus Sap on Prostate Cancer Cells

[0164] The ability of E. peplus sap to kill prostate cancer cells selectively was assessed by comparing the effect of the sap on prostate cancer cell lines and on normal fibroblasts. Three prostate cancer cell lines were used; PC-3 and DU145 are hormone resistant prostate cancer cell lines and LNcap is a hormone-sensitive prostate cancer cell line.

[0165] The prostate cancer cell lines or normal fibroblasts were suspended to a concentration of 5 X 10.sup.3 cells / well in RPMI1640 tissue cultmue medium containing 10% w / v FCS, volume 0.1 ml in microtitre plates.

[0166] The cells were incubated for 6 hr at 37.degree. C., followed by the addition of E. peplus crude sap (approximately 110 mg dry solids per ml) to the final dilutions, as shown in FIG. 1. After 5 days, cells were scored visually for survival morphology changes and survival was also assessed by .sup.3H-thymidine incorporation into cell mass. The results are expressed as percentag...

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Abstract

A chemical agent of the diterpene family obtained from a member of the Euphorbiaceae family of plants for use in the treatment of prophylaxis of prostate cancer or a related cancer or condition.

Description

[0001] The present invention relates generally to chemical agents useful in treatment and prophylaxis of prostate cancer or a related cancer or condition or in the amelioration of symptoms resulting from or facilitated by prostate cancer or a related cancer or condition in a mammalian animal including human or pR.sub.1mate. More particularly, the present invention provides a chemical agent of the diterpene family obtained from a member of the Euphorbiaceae family of plants or botanical or horticultural relatives thereof or deR.sub.1vatives or chemical analogs or chemically synthetic forms of the agents for use in the treatment or prophylaxis of prostate cancer or a related cancer or condition or in the amelioration of symptoms resulting from or facilitated by prostate cancer or a related cancer or condition in a mammal and in particular a human. The present invention further contemplates a method for the prophylaxis or treatment of a mammalian subject presenting with prostate cancer...

Claims

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Application Information

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IPC IPC(8): A61K31/22A61K31/222A61K31/235A61K31/455A61K31/66A61K31/662A61K31/695A61K36/00A61K36/47A61K38/00A61K39/395A61K45/00A61K47/48A61P35/00C07F9/40C07K14/705C07K16/30C12N5/07C12N5/077C12N5/0781C12N5/0783C12N5/09
CPCA61K31/222A61K31/235A61K47/48084A61K36/47A61K47/48023A61K31/455A61K47/54A61K47/548A61P35/00
Inventor AYLWARD, JAMES HARRISONPARSONS, PETER GORDON
Owner PEPLIN RES
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