Naproxen and omeprazole combination effective in preventing bladder cancer

The anti-inflammatory class of drugs NSAIDs have shown great promise in preventing cancers including colon, esophagus and skin. However, they can increase the risks of heart attacks, ulcers and rare but potentially life-threatening bleeds.

A new study suggests there may be ways to reduce these dangerous side effects. Collaborators from the University of Michigan, the National Cancer Institute and the University of Alabama looked at naproxen, which is known to have a lower cardiovascular risk than other NSAIDs. Naproxen, like most NSAIDs and aspirin, does increase the risk for gastric ulcers or bleeding. Here, the researchers used the proton pump inhibitor omeprazole, a commonly used acid inhibitor, in combination with naproxen and tested its effects on cancer prevention in a rat model of bladder cancer.

They found that naproxen reduced the incidence of bladder cancer by 75 percent in rats. Omeprazole by itself did not affect the development of cancer but it also did not interfere with the effect of naproxen at preventing tumors. The rats who received naproxen alone or naproxen with omeprazole developed cancer at similarly low rates, while all rats receiving omeprazole alone or no treatment developed bladder cancer.

Clinical data in humans has previously shown combining omeprazole plus naproxen reduced gastric toxicity roughly 70 percent.

The authors also found that intermittent dosing with naproxen (three weeks on the drugs, followed by three weeks off) was highly effective and likely to reduce gastric toxicity. However, it does not have the clear clinical data supporting reduced gastric toxicity associated with naproxen and omeprazole.

"Our study shows that naproxen works just as well with a proton pump inhibitor as without. This provides proof of principle that this could be a valuable cancer prevention strategy and one hopes it can advance quickly to a clinical trial for those at high risk of colon, esophageal, squamous cell skin cancer or potentially other cancers," says lead study author Ronald A. Lubet, Ph.D., a scientist with the Chemopreventive Agent Development Research Group at the National Cancer Institute.

Naproxen and omeprazole combination effective in preventing bladder cancer

New drug shows promise in driving insulin-producing beta cells to multiply

In a screen of more than 100,000 potential drugs, only one, harmine, drove human insulin-producing beta cells to multiply, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai, funded by JDRF and the National Institutes of Health, and published online today in Nature Medicine.

Diabetes results from too few insulin-producing "beta cells" in the pancreas secreting too little insulin, the hormone required to keep blood sugar levels in the normal range. The disease affects 380 million people worldwide, and leads to major medical complications: heart attack, stroke, kidney failure, blindness and limb amputation.

The Mount Sinai study found that harmine drove the sustained division and multiplication of adult human beta cells in culture, a feat that had eluded the field for years. In addition, harmine treatment tripled the number of beta cells and led to better control of blood sugar in three groups of mice engineered to mimic human diabetes.

"Our results provide a large body of evidence demonstrating that the harmine drug class can make human beta cells proliferate at levels that may be relevant for diabetes treatment," said senior study author Andrew Stewart, MD, Director of the Diabetes, Obesity and Metabolism Institute at the Icahn School of Medicine. "While we still have a lot of work to do in improving the specificity and potency of the harmine and related compounds, we believe these results represent a key step toward more effective future treatment of diabetes."

Loss of insulin-producing beta cells has long been recognized as a cause of Type 1 diabetes, in which the immune system mistakenly attacks and destroys beta cells. In recent years, researchers have concluded that a deficiency of functioning beta cells also contributes importantly to Type 2 diabetes. Thus, developing drugs that can increase the numbers of healthy beta cells is a major priority in diabetes research.

Ref : http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3820.html

New drug shows promise in driving insulin-producing beta cells to multiply

New injectable polymer could strengthen blood clots

In the initial study with rats, 100 per cent of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. Only 20 per cent of rats treated with a natural protein that helps blood clot survived.

“Most of the patients who die from bleeding die quickly,” said co-author Dr. Nathan White, an assistant professor of emergency medicine who teamed with UW bioengineers and chemical engineers to develop the macromolecule. “This is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”

According to a statement, the UW team was inspired by factor XIII, a natural protein found in the body that helps strengthen blood clots.

Normally after an injury, platelets in the blood begin to congregate at the wound and form an initial barrier. Then a network of specialised fibres called fibrin start weaving themselves throughout the clot to reinforce it.

New injectable polymer could strengthen blood clots

New cancer drug enters phase I clinical trials in humans

"Even though they have elevated levels of procaspase-3, cancer cells never turn the enzyme on. So they keep growing and become tumors," he said. "PAC-1 restores the activity of procaspase-3 and, because the enzyme is elevated in cancer cells, it targets cancer cells over non-cancerous cells."  

A new drug that prompts cancer cells to self-destruct while sparing healthy cells is now entering phase I clinical trials in humans. The drug, called PAC-1, first showed promise in the treatment of pet dogs with spontaneously occurring cancers, and is still in clinical trials in dogs with osteosarcoma.

The compound was discovered and is being developed based on the hypothesis that most cancers have elevated levels of an enzyme called procaspase-3," said University of Illinois chemistry professor Paul Hergenrother, who discovered the anti-cancer effects of PAC-1 more than a decade ago. "Procaspase-3 is an enzyme that, when turned on, kills cells."

Cancer cells, however, override this normal cell-recycling pathway, he said.

Early tests of the drug's effectiveness came when Hergenrother collaborated with U. of I. veterinary clinical sciences professor Timothy Fan, who tested PAC-1 in his canine cancer patients. These clinical trials helped the researchers find the best way to deliver the drug - it is now in pill form for both human and canine patients - and led to new insights into the drug's activity and potential, Fan said.

New cancer drug enters phase I clinical trials in humans

EMA extends approval of Vectibix plus FOLFIRI as first-line treatment for wild-type RAS mCRC

Amgen (NASDAQ: AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the marketing authorization for Vectibix® (panitumumab) to include combination with FOLFIRI- FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs:

• FOL – folinic acid (leucovorin), a vitamin B derivative used as a "rescue" drug for high doses of the drug methotrexate, but increases the cytotoxicity of 5-fluorouracil;
• F – fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops synthesis; and
• IRI – irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.

 (an irinotecan-based chemotherapy) as first-line treatment in adult patients with wild-type RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have wild-type RAS tumors.

"Adding Vectibix to chemotherapy as first-line treatment in patients with wild-type RASmetastatic colorectal cancer has been shown to result in better responses than chemotherapy alone," said Elliott M. Levy, M.D., senior vice president of Global Development at Amgen. "The CHMP recommendation is an important step toward increasing the treatment options for patients with this aggressive disease and helping improve outcomes in the European Union."

EMA extends approval of Vectibix plus FOLFIRI as first-line treatment for wild-type RAS mCRC

EMA's CHMP backs JINARC (tolvaptan) for autosomal dominant polycystic kidney disease

Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolsama & Tolvat and by Lupin under the brand name Resodim.

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Otsuka Pharmaceutical Co., Ltd. announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended JINARC® (tolvaptan) for approval. This treatment has been recommended to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease.

Tolvaptan was developed over a period of 26 years through the persevering efforts of researchers in Otsuka’s Japanese pharmaceutical research centre. Upon discovering a cell signaling pathway that causes renal cysts to proliferate and enlarge, Otsuka launched an effort in 2004 to develop a drug for the disease in conjunction with the world’s leading ADPKD medical specialists.

EMA's CHMP backs JINARC (tolvaptan) for autosomal dominant polycystic kidney disease

Study shows efficacy of YONDELIS (trabectedin) in patients with soft-tissue sarcoma

In continuation of my update on trabectedin

PharmaMar announced that the European Journal of Cancer published online data from a large retrospective study with soft-tissue sarcoma (STS) patients carried out at 25 French centers confirming that in routine practice YONDELIS® (trabectedin) shows comparable or better clinical outcomes than those observed in clinical trials . The results add to previous evidence from other studies with trabectedin , including the compassionate expanded access program of 1895 patients with incurable disease , demonstrating that response and disease control rates are higher than expected. The authors describe that long-term treatment of multiple types of STS patients without progressive disease delayed progression and improved survival compared to those who stopped it after six cycles, as recently suggested in the T-DIS studyiii. In this routine real-life scenario, the median progression-free survival (PFS) and overall survival (OS) were 4.4 and 12.2 months, respectively after a median follow-up of 22 month. Of the 304 patients who achieved non-progressive disease after six cycles, 227 continued receiving trabectedin and obtained significant superior PFS (11.7 versus 7.6 months) and OS (24.9 versus 16.9 months) than those who did not. The recent study reinforces an approach of early administration of YONDELIS® (trabectedin) to optimize its efficacy as second-line treatment in patients that will probably benefit from this drug. Despite the limitations of the study, the investigators emphasize that this clinical strategy may achieve longer disease control without compromising the safety profile of the treatment, given that a third of the patients received more 6 or more cycles of the drug and were able to tolerate longer treatments.

Study shows efficacy of YONDELIS (trabectedin) in patients with soft-tissue sarcoma

Bionomics to present data from DisrupTOR-1 trial at ASCO Genitourinary Cancers Symposium

Bionomics Limited (ASX:BNO, ADR:BMICY) is to present important additional data from the DisrupTOR-1 trial of BNC105 in patients with metastatic renal cancer at the ASCO Genitourinary Cancers Symposium in Orlando, Florida. The data will be presented by Dr. Sumanta Pal of the City of Hope Comprehensive Cancer Center in California in his poster presentation.

The new data identifies Ferritin and IL-8 as two baseline biomarkers that correlate with an improved progression free survival (PFS) in patients. Elevated baseline Ferritin and lower baseline IL-8 were associated with improved PFS (P=0.0291 and P=0.0149, respectively). Eighty nine percent of patients expressing elevated plasma levels of Ferritin and lower plasma levels of IL8 at baseline were disease progression free (PFS) at 6 months.

"The DisrupTOR-1 trial offered a unique opportunity to assess biomarkers related to the activity of BNC105. Interestingly our findings suggest that baseline levels of Ferritin and IL-8 may predict an excellent clinical outcome with the combination of Afinitor with BNC105. Plans are underway already to validate this finding in a biomarker-driven trial," said Dr. Pal, Co-Director of the Kidney Cancer Program at the Department of Medical Oncology & Experimental Therapeutics of the City of Hope Comprehensive Cancer Center.

"This is a compelling improvement compared to the 34% PFS observed at six months in the unselected population," said Dr. Deborah Rathjen, Bionomics' CEO and Managing Director.

"These results indicate that moving forward, biomarker-based patient selection has the potential to provide guidance and optimise clinical outcomes in the treatment of renal cancer, presenting a range of new possibilities for BNC105. We will continue to explore further data and the options for the advancement of the compound.

"Bionomics to present data from DisrupTOR-1 trial at ASCO Genitourinary Cancers Symposium

Sorafenib, sunitinib provide no benefit to patients with locally advanced kidney cancer

Findings from a federally funded study suggest that patients with locally advanced kidney cancer should not be treated with either adjuvant (post-surgery) sorafenib or sunitinib. The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery (5.6 years) and those treated with placebo (5.7 years). The study will be presented at the upcoming 2015 Genitourinary Cancers Symposium in Orlando.

"These drugs didn't reduce disease recurrence, but on average they did not appear to worsen patient outcomes either," said lead study author Naomi B. Haas, MD, an Associate Professor of Medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, Pa. "We are still analyzing the various groups of patients enrolled on this trial, and we hope that analysis of patient specimens collected on this study may provide clues into subsets of patients who might still benefit from these therapies."

Sorafenib, sunitinib provide no benefit to patients with locally advanced kidney cancer

Treatment reduces risk of recurrence of C. difficile infection

In continuation of my update on metronidazole  &  vancomycin

Among patients with Clostridium difficile infection (CDI) who recovered following standard treatment with the antibiotics metronidazole or vancomycin, oral administration of spores of a strain of C difficilethat does not produce toxins colonized the gastrointestinal tract and significantly reduced CDI recurrence, according to a study in the May 5 issue of JAMA.

C difficile is the cause of one of the most common and deadly health care-associated infections, linked to 29,000 U.S. deaths each year. Rates of CDI remain at unprecedented high levels in U.S. hospitals. Clinical infection also has a recurrence rate of 25 percent to 30 percent among affected patients. Not all strains of C difficile produce toxins. Nontoxigenic C difficile strains that lack the genes for toxin production are also found in the hospital environment and can colonize hospitalized patients, although patients are usually asymptomatic. Gastrointestinal colonization by these nontoxigenic C difficilestrains (in both humans and hamsters) has shown promising results as a potential way to prevent CDI, according to background information in the article.

Dale N. Gerding, M.D., of the Edward Hines Jr. VA Hospital, Hines, Il., and Loyola University Chicago, Maywood, Il., and colleagues randomly assigned 173 adult patients who were diagnosed as having CDI (first episode or first recurrence) to receive 1 of 4 treatments: oral liquid formulation of nontoxigenic C difficile strain M3 (VP20621; NTCD-M3), 104 spores/d for 7 days (n = 43), 107 spores/d for 7 days (n = 44), 107 spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). Prior to enrollment, these patients had all successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe.

Treatment reduces risk of recurrence of C. difficile infection