News Column

Patent Issued for Methods and Compositions for Inhibiting the Proliferation of Cancer Cells

August 25, 2014

By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- University of Central Florida Research Foundation, Inc. (Orlando, FL) has been issued patent number 8802649, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also University of Central Florida Research Foundation, Inc.).

The patent's inventor is Chakrabarti, Ratna (Winter Springs, FL).

This patent was filed on April 4, 2013 and was published online on August 12, 2014.

From the background information supplied by the inventors, news correspondents obtained the following quote: "The following is offered as background information only and is not admitted to be prior art to the present invention.

"Cancer cells are characterized by an ability to proliferate indefinitely and to invade normal tissue cells surrounding a cancerous tumor. In addition, many types of cancer cells can metastasize throughout the body whereby the tumor may be disseminated in the cancer patient's body.

"The mechanism of cancer metastasis is presumed as follows: (1) cancer cells proliferate in a primary cancer colony; (2) blood vessels are newly formed; (3) the malignant cancer cells infiltrate and penetrate the newly formed blood vessels; (4) the cancer cells circulate within the human body; (5) the cancer cells reach a target organ; (6) the cancer cells extravasate from blood vessels; (7) the cancer cells proliferate in the target organ; and (8) a metastatic focus is formed.

"The cure rate of malignant cancer tumors has increased with early diagnosis and with the progress of therapies, but metastases of malignant tumors are often beyond current therapies. Chemotherapies are used to arrest metastases following removal of tumors but often with unsatisfactory results. It is therefore desirable to develop more effective inhibitors against malignant tumor metastases.

"Conventional methods for treating cancer have also increased the survival and quality of life for cancer patients. Such conventional methods include surgery, for example, removal of the prostate gland (radical prostectomy), radiotherapy, and chemotherapy. In addition, bone marrow transplantation is becoming useful in treating patients with certain types of cancers.

"Combination therapies may be used in treating cancer and are typically not addictive. In some cases, cross effects and treatment load can result in a lower effectiveness for the combinations, than either treatment alone.

"Other treatments such as radiation, while useful for a wide range of cancers, does not typically result in a complete cure. Given the severity of many cancers and the mortality rate, a drug may be thought of as successful if it improves the quality of life by delaying the growth of tumors, or if it prolongs life without actually curing the condition. In many circumstances, an individual is treated with a specific composition or with a combination of therapies that can eliminate from about 90 to about 95% of the malignant cells, but the remaining cells can re-grow and metastasize, ultimately resulting in death.

"LIM kinase 1 (LIMK 1) is one of the regulatory proteins that modulate the actin cytoskeleton by inactivating an actin-binding protein, cofilin, through addition of a phosphate group to cofilin. Actin cytoskeleton is maintained by the constant severing and joining of small units of actin and any deviation away from this normal dynamic may lead to abnormal behavior of a particular cell. LIMK1 plays an important role in maintaining cell architecture through actin cytoskeleton. As an important regulator of cell behavior, levels of LIMK1 need to be regulated in cells for the maintenance of normal cellular function. The concentration of LIMK1 has previously been found at increased levels in some cancer cells; for example, cancer cells that are highly aggressive and capable of causing metastasis or the spread of tumors in mice. Research has shown that a partial inhibition of LIMK 1 synthesis using antisense RNA in these cells resulted in the inhibition of cell growth and more specifically, regression of the invasive property of these cells.

"Efforts to identify compositions which inhibit the expression of LIMK 1 and, which therefore, should be useful in the treatment and prevention of cancer cell metastasis, has led to the use of the 'antisense' or non-encoding LIM Kinase 1, which exhibits an ability to inhibit the expression of LIMK 1 in certain cancer cells.

"Antisense RNA mediated gene therapy is a widely used method of gene inactivation and is suitable for gene therapy use. However, RNA mediated gene inactivation does not work for all genes, and may not be used as a global method of gene inactivation."

Supplementing the background information on this patent, NewsRx reporters also obtained the inventor's summary information for this patent: "Before explaining the disclosed embodiment of the present invention in detail it is to be understood that the invention is not limited in its application to the details of the particular arrangement shown since the invention is capable of other embodiments. Also, the terminology used herein is for the purpose of description and not of limitation.

"In one embodiment, the present invention provides, for example, a method for treating cancers and individuals at risk of developing cancers by administering an antisense RNA of LIM Kinase 1.

"In another embodiment, the present invention indicates that the expression of LIM kinase, one of the proteins that modulates actin dynamics, is over expressed in denocarcinomatous prostatic epithelium and cancer cell lines.

"In one embodiment of the present invention, there is provided an advantageous therapy for inhibiting the metastasis of cancers cells, including, for example, breast, ovarian, lung, and prostate cancer cells. More specifically, the invention, in embodiments relates to the use of LIM kinase 1 antisense RNA to reduce the synthesis of endogenous LIM kinase 1 in prostate cancer cell lines. This reduction has been shown to reduce the number of metastizing cancer cells.

"In another embodiment of the invention, a partial reduction of LIMK1 altered cell proliferation by arresting cells at the G2/M phase of the cell cycle. Data has also shown a changed cell shape and the associated inhibition of the invasive tendencies of metastatic prostate cancer cells. Ectopic expression of LIMK1 promotes the acquisition of the invasive phenotype by benign prostate epithelial cells. Experimental data provides evidence of a novel role of LIMK1 in regulating cell division and in regulating the invasive properties of prostate cancer cells.

"In yet another embodiment of the invention, results indicate that the invasive properties of prostate cancer cells is not mediated by phosphorylation of cofilin. Experimental data correlates with the recent observations showing a metastasis-associated chromosomal gain of 7q11.2 in prostate cancer, suggesting a possible gain in LIMK1 DNA (7q11.23).

"Yet another embodiment of the instant invention comprises partial amino acid and nucleotide sequences of LIMK1.

"In still another embodiment of the present invention results indicate that the antisense RNA of LIM kinase 1 can be used successfully in the functional inactivation of LIM kinase 1.

"In other embodiments of the present invention, antisense RNA may be used, for example, to inhibit gene function and to demonstrate that the LIMK1 gene may find use, for example, as a therapeutic target for developing effective cancer drugs.

"In yet another embodiment results indicated, for the first time, that LIMK 1 may find use as a novel target for anti sense RNA mediated gene inactivation. Results also indicate that the expression of LIMK 1 may be used as a predictive marker for prostate cancer cell metastasis."

For the URL and additional information on this patent, see: Chakrabarti, Ratna. Methods and Compositions for Inhibiting the Proliferation of Cancer Cells. U.S. Patent Number 8802649, filed April 4, 2013, and published online on August 12, 2014. Patent URL:

Keywords for this news article include: Antisense Technology, Biotechnology, Genetics, Oncology, Lim Kinases, Cytoskeleton, Bioengineering, Cancer Gene Therapy, Cellular Structures, Intracellular Space, Enzymes and Coenzymes, Cytoplasmic Structures, Intracellular Signaling Peptides and Proteins, University of Central Florida Research Foundation Inc.

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Source: Cancer Gene Therapy Week

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