Bovine lactalbumin complex with lipid(NatImmune A/S)

To document the efficacy and tolerability of 14‐day bismuth–lansoprazole–amoxicillin–clarithromycin (BLAC) regimen for Helicobacter pylori (H. pylori) eradication as a first‐line therapy.

Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and H. pylori infection was diagnosed through histologic examination of antral and body biopsy samples. Primary end point of this study was to evaluate the eradication rate of 14‐day BLAC regimen therapies. H. pylori eradication was assessed using the 13C urea breath test performed 6 weeks after the completion of treatment. All patients were asked to fill in a validated questionnaire to report therapy‐related side effects. Each symptom was graded from absent or present.

Ninety‐seven (21 men and 76 women) were enrolled. All the patients completed the study. The H. pylori eradication rate was 90.7% (88 of 97 patients). Side effects were observed in reasonable percentages, and none of the patients left the study because of drug side effect.

Bismuth–lansoprazole–amoxicillin–clarithromycin regimen as a 2‐week course achieved an acceptable eradication rate with relatively mild side effects.

Novel intravesical therapies are needed for superficial bladder cancer that reduce the risk of infection associated with B acillus C almette– G uérin ( BCG ) and further destabilization of the urothelium associated with cytotoxic chemotherapy. Experimental therapies to date have included photodynamic therapy, oncolytic viruses, gene therapy (antisense oligonucleotides and silencing RNA ), cytokine therapy, death receptor agonists (tumour‐necrosis‐factor‐related apoptosis‐inducing ligand and anti‐ DR 5 monoclonal antibody), naturally occurring substances (curcumin and deguelin) and human α‐lactalbumin made lethal to tumour cells ( HAMLET ). HAMLET , a natural occurring product in milk, induces apoptosis in urothelial cancer cells but has limitations in clinical application because of its human source. A previous study in patients with bladder cancer has demonstrated that intravesical HAMLET (daily for 5 days before tumour resection) caused selective apoptotic tumour cell death. BAMLET , the bovine equivalent of HAMLET , is a complex of bovine α‐lactalbumin and oleic acid ( bLAC ) that has been shown in vitro to accumulate in the endolysosomal compartment of tumour cells and induce leakage of lysosomal cathepsins into the cytosol followed by activation of the pro‐apoptotic protein Bax. This is the first in vivo study to show that BAMLET ( bLAC ) induces apoptosis in urothelial cancer cells and controls the growth of high risk urothelial cancer in a syngeneic rat orthotopic model. This same bladder cancer model system has been used to test other novel therapies, including BCG , and therefore provides a relative comparison of its effectiveness with other intravesical therapies.

To investigate the efficacy of a complex of bovine α‐lactalbumin and oleic acid ( bLAC ) to kill urothelial cancer cells in vitro and inhibit tumour growth and progression in a high risk bladder tumour model.

The cytotoxicity of bLAC to a large panel of urothelial cell cancer ( UCC ) cells was tested by the MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2 H ‐tetrazolium bromide) assay, using bLA , the folded α‐lactalbumin without oleic acid, as a control. The mechanism of bLAC ‐inducing cell death was evaluated by annexin V staining, TUNEL (terminal deoxynucleotidyl transferase mediated nick end labelling) assay and sub‐ G1DNA analysis. The selective bLAC cytotoxicity was examined using multicellular spheroids consisting of UCC and non‐transformed fibroblasts. Rats bearing orthotopic tumour received intravesical instillations (twice weekly, for 3 weeks) of bLAC , bLA , BCG or saline, starting 6 days after UCC ( AY ‐27) cell inoculation. Animals were monitored for survival, toxicity and tumour growth control.

A dose‐dependent bLAC ‐inducing apoptotic‐like cell death was shown in UCC cells tested, including cells refractory to classic apoptosis‐inducing agents, whereas b LA showed little cytotoxicity. bLAC selectively destroyed cancer cells in spheroids. Intravesical bLAC therapy demonstrated marked reduction in tumour growth/progression and significantly prolonged animal survival vs saline instillations ( P = 0.004, log‐rank test) and showed comparable efficacy with BCG (standard) therapy.

The findings identify bLAC as a new candidate for UCC therapy and suggests that topical administration of bLAC alone or with BCG to prevent progression of bladder cancer warrants further exploration.