montelukast and Colonic-Neoplasms

Rapid desensitization is a process in which drug-allergic patients receive their target dose in incremental steps, resulting in a state of temporary tolerization. In this manner, first-line therapy can be delivered safely, even in patients who present with severe hypersensitivity reactions (HSRs) to the given agent. A small subset of patients has persistent HSRs during rapid desensitization that can be refractory to antihistamines and corticosteroids.. To increase the safety and tolerability of rapid desensitization by prostaglandin and leukotriene blockade in patients with refractory mast cell mediator-related symptoms.. Fourteen adult patients developed HSRs to platinum chemotherapy that persisted during rapid desensitization. All patients had cutaneous symptoms (flushing, pruritus, or urticaria), many with associated systemic reactions. These patients were then pretreated with acetylsalicylic acid, 325 mg orally, and montelukast, 10 mg orally, 2 days before and on the day of desensitization. Response to subsequent desensitizations was assessed by medical record review and was compared with a group of matched historic control patients who received methylprednisolone for HSRs during desensitization.. Seventy-eight desensitizations in 14 patients were performed. Using acetylsalicylic acid and montelukast, 86% of patients (12/14) experienced substantial improvement in symptoms (grade 0.5 vs grade 2.14, P < .0001). Reduction in symptoms during desensitization was also significantly greater than that experienced by historic control patients who received methylprednisolone pretreatment (grade 0.5 vs grade 1.75, P = .0008). All patients received their target dose of chemotherapy, and there were no severe systemic HSRs.. Pretreatment with acetylsalicylic acid and montelukast lessens the severity of HSRs during rapid desensitization.

Topics: Acetates; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Aspirin; Colonic Neoplasms; Cyclopropanes; Desensitization, Immunologic; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Inflammation Mediators; Mast Cells; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Quinolines; Reference Standards; Sulfides

Inflammation is implicated in the etiology of sporadic colon cancer (CC), which is one of the leading causes of cancer-related deaths worldwide. Here, we report that inhibition of the inflammatory receptor CysLT

Topics: Acetates; Animals; Cell Line, Tumor; Colonic Neoplasms; Cyclopropanes; Female; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Leukotriene Antagonists; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Quinolines; Receptors, Leukotriene; Sulfides; Tumor Burden; Xenograft Model Antitumor Assays

We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlu kast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.

Topics: Acetates; Animals; Capillary Permeability; Carcinoma, Lewis Lung; Cell Line, Tumor; Chromones; Colonic Neoplasms; Cyclopropanes; Female; Leukotriene Antagonists; Male; Mice; Neoplasm Metastasis; Neoplastic Cells, Circulating; Quinolines; Rats; Rats, Inbred F344; Sulfides