Chondroitin sulfate

Researchers have designed cancer-fighting nanoparticles that co-deliver a chemotherapy drug and a novel immunotherapy, according to a new study. University of Pittsburgh researchers have designed cancer-fighting nanoparticles that co-deliver a chemotherapy drug and a novel immunotherapy, according to a new Nature Nanotechnologystudy published today. The new immunotherapy approach silences a gene that the researchers discovered was involved in immunosuppression. When combined with an existing chemotherapy drug and packaged into tiny nanoparticles, the therapy shrunk tumors in mouse models of colon and pancreatic cancer. "There are two innovative aspects of our study: the discovery of a new therapeutic target and a new nanocarrier that is very effective in selective delivery of immunotherapy and chemotherapeutic drugs," said senior author Song Li, M.D., Ph.D., professor of pharmaceutical sciences in the Pitt School of Pharmacy and UPMC Hillman Cancer Center investigator. "I'm excited about this research because it's highly translational. We don't know yet whether our approach works in patients, but our findings suggest that there is a lot of potential." Chemotherapy is a pillar of cancer treatment, but residual cancer cells can persist and cause tumor relapse. This process involves a lipid called phosphatidylserine (PS), which is usually found inside the tumor cell membrane's inner layer but migrates to the cell surface in response to chemotherapy drugs. On the surface, PS acts as an immunosuppressant, protecting remaining cancer cells from the immune system. The Pitt researchers found that treatment with chemotherapy drugs fluorouracil and oxoplatin (FuOXP) led to increased levels of Xkr8, a protein that controls distribution of PS on the cell membrane. This finding suggested that blocking Xkr8 would prevent cancer cells from shunting PS to the cell surface, allowing immune cells to mop up cancer cells that lingered after chemotherapy. In an independent study that was recently published in Cell Reports, Yi-Nan Gong, Ph.D., assistant professor of immunology at Pitt, also identified Xkr8 as a novel therapeutic target to boost anti-tumor immune response. Li and his team designed snippets of genetic code called short interference RNA (siRNA), which shuts down production of specific proteins -- in this case, Xkr8. After packaging siRNA and FuOXP together into dual-action nanoparticles, the next step was targeting them to tumors. Nanoparticles are typically too large to cross intact blood vessels in healthy tissue, but they can reach cancer cells because tumors sometimes have poorly developed vessels with holes that allow them passage. But this tumor-targeting approach is limited because many human tumors do not have large enough holes for nanoparticles to pass through. "Like a ferry carrying people from one side of the river to the other, we wanted to develop a mechanism that allows nanoparticles to cross intact blood vessels without relying on holes," said Li. To develop such a ferry, the researchers decorated the surface of the nanoparticles with chondroitin sulfate and PEG. These compounds help the nanoparticles target tumors and avoid healthy tissue by binding to cell receptors common on both tumor blood vessels and tumor cells and prolonging the length of time they remain in the bloodstream. When injected into mice, about 10% of the nanoparticles made their way to their tumor -- a significant improvement over most other nanocarrier platforms. A previous analysis of published research found that, on average, only 0.7% of nanoparticle doses reach their target. The dual-action nanoparticles dramatically reduced the migration of immunosuppressing PS to the cell surface compared to nanoparticles containing the chemodrug FuOXP alone. Next, the researchers tested their platform in mouse models of colon and pancreatic cancer. Animals treated with nanoparticles containing both FuOXP and siRNA had better tumor microenvironments with more cancer-fighting T cells and fewer immunosuppressive regulatory T cells than animals that received placebo or FuOXP doses. As a result, mice that received the siRNA-FuOXP nanoparticles showed a dramatic decrease in tumor size compared to animals that received those carrying just one therapy. According to Li, the study also pointed to the potential of combining the FuOXP-siRNA nanoparticles with another type of immunotherapy called checkpoint inhibitors. Immune checkpoints such as PD-1 act like brakes on the immune system, but checkpoint inhibitors work to release the brakes and help immune cells to fight cancer. The researchers found that FuOXP nanoparticles with or without siRNA increased PD-1 expression. But when they added a PD-1 inhibitor drug, the combination therapy had drastic improvements in tumor growth and survival in mice. With their sights set on translating their novel therapy to the clinic, the team is now looking to validate their findings with additional experiments and further evaluate potential side effects. Other researchers who contributed to this study were Yuang Chen, M.S., Yixian Huang, Ph.D., Qinzhe Li, M.S., Zhangyi Luo, B.S., Ziqian Zhang, M.S., Haozhe Huang, M.S., Jingjing Sun, Ph.D., LinXinTian Zhang, B.S., Runzi Sun, Ph.D., Daniel J. Bain, Ph.D., James F. Conway, Ph.D., and Binfeng Lu, Ph.D., all of Pitt or UPMC. This work was supported by the National Institutes of Health (R01CA219399, R01CA223788 and R01CA219716).

SAN DIEGO and MILTON, Ontario, Jan. 3, 2012 (GLOBE NEWSWIRE) -- Apricus Biosciences, Inc. ("Apricus Bio") (Nasdaq:APRI - News) ( ) and Stellar Pharmaceuticals Inc. ("Stellar Pharma") (OTCQB:SLXCF.PK - News) (OTCBB:SLXCF.PK - News) (Pink Sheets:SLXCF), a Canadian public company, announced today the signing of an exclusive license agreement. Under the agreement, Stellar Pharma has the exclusive right to sell Apricus Bio's MycoVa(TM) product for the treatment of onychomycosis (nail fungus) in Canada, following receipt of Canadian regulatory approval for such product. The exclusive license agreement provides for an upfront payment, regulatory approval milestone, sales achievement milestones and royalty payments during the term of the agreement. Onychomycosis is a chronic persistent fungal infection of the nail bed resulting in thickening and discoloration of the nail, which sometimes can be accompanied by serious pain and disability. According to the Merck Manual, the worldwide incidence rate of onychomycosis is approximately 10%. As described by Iorizzo and Piraccini (2007), the incidence has been increasing due to diabetes, immunosuppression and an aging population. While occurring in approximately 2.6% of children younger than 18 years, it occurs in as much as 90% of the elderly population (eMedicine.medscape.com). As of 2008, Thomson Reuters Pharma had stated that the worldwide market was approximately $2.8 billion in size and is expected to grow to approximately $2.9 billion by 2014. The advantage of Apricus Bio's MycoVa(TM) product is that it is easy to apply, and is therefore believed to improve patient compliance. MycoVa(TM) is applied to the infected nails, typically at bedtime, with minimal preparation, such as simply washing with soap and water. The formulation allows significant amounts of the drug to penetrate through the nail plate to the nail bed and surrounding area where fungus is located without significant systemic exposure. Dr. Bassam Damaj, Chairman, President and Chief Executive Officer of Apricus Bio commented, "We are very pleased with our exclusive license agreement with Stellar Pharma and we look forward to the future commercialization in the Canadian market of MycoVa(TM), our second major product utilizing our proprietary NexACT(R) technology. We are very impressed with the experience of Rob Harris and his team at Stellar Pharma, and we are very excited about this first potential launch of this important drug in that market. We also hope that our partnership with Stellar Pharma will produce additional collaborations among multiple NexACT(R) products in the future." Rob Harris, President and Chief Executive Officer of Stellar Pharma stated, "We are excited about this opportunity and are very pleased to be able to strengthen our dermatology portfolio in Canada. I would like to thank Bassam and his excellent team at Apricus Bio for providing us with this opportunity to launch MycoVa(TM) in the Canadian market. We will be assisting Apricus Bio in the filing of a New Drug Submission for MycoVa(TM) for onychomycosis and look forward to its commercial launch in Canada following Canadian regulatory approval." About MycoVa(TM) MycoVa(TM) combines an existing, approved drug for nail fungus, terbinafine, with the NexACT(R) technology that enhances the absorption of the drug through the skin. In January 2011, the Company announced that an additional analysis showed that MycoVa(TM) is as effective for the treatment of nail fungus as the current European standard of care for topical therapy, Loceryl(R) (an ointment made by Galderma). In June 2011, the Company announced that based on a reanalysis of its Phase III trials for its MycoVa(TM) product for treating onychomycosis (nail fungus), it is revisiting its regulatory strategy for the drug and will seek guidance from regulatory authorities in the U.S., Canada and Europe. A combined post-hoc analysis of two randomized, double-blind, vehicle controlled, multicenter, parallel group Phase III studies to assess the efficacy, safety and tolerability of MycoVa(TM) demonstrated statistically significant results in primary and secondary efficacy endpoints in favor of active treatment in patients who did not present with comorbid tinea pedis (athlete's foot), as these patients are considered at higher risk of reinfection. About Apricus Biosciences, Inc. Apricus Bio is a San Diego-based, revenue-generating, specialty pharmaceutical company, with commercial products and a broad pipeline across numerous therapeutic classes. Revenues and growth are driven from the sales of the Company's commercial products through its Apricus Pharmaceuticals USA, Inc. and NexMed (USA), Inc. subsidiaries and through out-licensing in certain territories of its product pipeline and NexACT(R) technology. Apricus Bio's current pipeline includes Vitaros(R), approved in Canada for the treatment of erectile dysfunction, Totect(R) the only drug approved in the US for the treatment of anthracycline extravasation, as well as compounds in development from pre-clinical through pre-registration currently focused on Sexual Dysfunction, Oncology, Dermatology, Autoimmune, Pain, Anti-Infectives, Diabetes and Consumer Healthcare. The Company also expects to develop and/or acquire and then bring to market additional pharmaceutical products in areas of care that will benefit patient needs worldwide. For further information on Apricus Bio, visit and for information on its subsidiary please visit You can also receive information at and About Stellar Pharmaceuticals Inc. Stellar Pharma and its subsidiary, Tribute Pharmaceuticals, is an emerging Canadian specialty pharmaceutical company focused on the acquisition, licensing, development and management of pharmaceutical and healthcare products with its primary focus on the Canadian market. Stellar Pharma currently competes in the dermatology market in Canada with its promotion of Soriatane(R)* (acitretin). Stellar Pharma also markets Bezalip(R)* SR (bezafibrate), NeoVisc(R) (1.0% sodium hyaluronate solution) and Uracyst(R) (sodium chondroitin sulfate solution 2%) in the Canadian market place and is awaiting regulatory approval for Cambia(R)** (diclofenac potassium for oral solution) in Canada. Additionally, NeoVisc(R) and Uracyst(R) are commercially available in 58 countries and are sold globally through various international partnerships. Stellar Pharma is currently in negotiations to license both NeoVisc(R) and Uracyst(R) in the US and other international markets. For further information on Stellar Pharma, visit and for information on its subsidiary please visit Apricus Bio's Forward-Looking Statement Safe Harbor Statements under the Private Securities Litigation Reform Act, as amended: with the exception of the historical information contained in this release, the matters described herein contain forward-looking statements that involve risks and uncertainties that may individually or mutually impact the matters herein described for a variety of reasons that are outside the control of the Company, including, but not limited to, its ability to receive issued patents on its NexACT(R) technology and products, develop such patented technology into product candidates, have its Rx Division products and product candidates such as Vitaros(R) and MycoVa(TM) approved by relevant regulatory authorities and its Consumer Healthcare Division products either approved or cleared by relevant regulatory authorities or be in compliance with appropriate regulatory requirements, to successfully manufacture and commercialize such Rx Division products as Totect(R) for the treatment of anthracycline extravasation, Vitaros(R) for erectile dysfunction and MycoVa(TM) for onychomycosis in the U.S., Canada, and in other countries along with its Consumer Healthcare Division products and product candidates and to achieve its other development, commercialization and financial goals. Readers are cautioned not to place undue reliance on these forward-looking statements as actual results could differ materially from the forward-looking statements contained herein. Readers are urged to read the risk factors set forth in the Company's most recent annual report on Form 10-K, subsequent quarterly reports filed on Form 10-Q and other filings made with the SEC. Copies of these reports are available from the SEC's website or without charge from the Company. Stellar Pharmaceuticals' Forward Looking Statement This press release contains certain forward-looking statements about Stellar Pharma as defined in the Private Securities Litigation Reform Act of 1995, which statements can be identified by the use of forward-looking terminology, such as "may", "will", "expect", "intend", "anticipate", "estimate", "predict", "plan" or "continue" or the negative thereof or other variations thereon or comparable terminology referring to future events or results. Forward-looking statements, by their nature, are subject to risks and uncertainties, Stellar Pharma's actual results could differ materially from those anticipated in these forward-looking statements as a result of numerous factors, including general economic conditions, the ability of Stellar Pharma to successfully integrate operations, and the timing of expenditures and expansion opportunities, any of which could cause actual results to vary materially from current results or anticipated future results. See Stellar Pharma's reports filed with the Canadian Securities Regulatory Authorities and the U.S. Securities and Exchange Commission from time to time for cautionary statements identifying important factors with respect to such forward-looking statements, including certain risks and uncertainties, that could cause actual results to differ materially from results referred to in forward-looking statements. Stellar Pharma assumes no obligation to update the information contained in this press release to update forward-looking statements to reflect changed assumptions, the occurrence of anticipated events or changes in future operating results, financial condition or business over time. *Soriatane and Bezalip are registered trademarks and under license from Actavis Group PTC ehf **Cambia is a registered trademark and under license from Nautilus Neurosciences, Inc. Contact: Apricus Biosciences, Inc.Edward Cox, V.P.Corporate Development & Investor Relations, Apricus Bio, Inc.(858) 848-4249ecox@apricusbio.comApricus Bio Investor RelationsPaula SchwartzRx Communications Group, LLC(917) 322-2216pschwartz@rxir.comStellar Pharmaceuticals Inc.Attention: Scott LangilleCFO(519) 434-1540scott.langille@stellarpharma.comAttention: Arnold TenneyChairman705-445-9505