title: Treatment of cancer cachexia in mice by combination of dsRNA-dependent             protein kinase inhibitor and medroxyprogesterone acetate.
abstract: Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone             acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare             these two drugs, alone or in combination, in cancer cachexia in mice. Forty male             BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo,             and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma             and fed for 12 days and then treated with PKRI and MPA alone or in combination             for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum             levels of nutritional markers and cytokines were measured. The tumor growth (volume             and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that             of placebo group. Wet weight of gastrocnemius muscle was significantly higher             in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing             mice had a significantly lower level of blood glucose, higher level of serum triglyceride             and lower level of serum albumin compared with healthy control (P<0.001). However,             PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose             and lower level of serum triglyceride compared with placebo group (P<0.001).             All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 and             IL-6 compared with healthy control (P<0.001). Serum level of TNF-α and IL-6             was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01).             PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may             alleviate cachexia.
authors.affiliation: Department of Gastro-intestinal Surgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chating Zhong Road, Fuzhou, Fujian 350005, PR China. chensz04871@hotmail.com
authors.forename: Si-Zeng
authors.initials: SZ
authors.lastname: Chen
authors.forename: Yong-Lian
authors.initials: YL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D047368:Tumor Burden / Q000187:drug effects; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D017258:Medroxyprogesterone Acetate; D019892:eIF-2 Kinase