Assessment of enthesopathy in conventional pelvis radiography: Another tool for spondyloarthritis diagnosis beyond sacroiliitis.

Introduction/objectives: Enthesitis is a cardinal feature of spondylarthritis (SpA), and the pelvis is a common site of enthesitis. This study aimed to establish the association between pelvic enthesis involvement on pelvic X-ray and SpA diagnosis through a radiographic enthesis index (REI) and to assess the reliability and accuracy of this REI.

Materials And Methods: The participants were SpA patients and a control group composed of patients with chronic lumbar pain without SpA.

Efficacy of EGFR Inhibitors and NSAIDs Against Basal Bladder Cancers in a Rat Model: Daily vs. Weekly Dosing, Combining EGFR Inhibitors with Naproxen, and Effects on RNA Expression.

Background: There are few effective treatments specifically aimed at basal bladder cancer.

Objective: Female F344 rats administered N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) develop large invasive bladder cancers. We determined the efficacy of daily vs weekly dosing of EGFR inhibitors, determined the efficacy of naproxen combined with an EGFR inhibitor, and performed RNA analysis of bladder tumors treated for 5 days with EGFR inhibitors or NO-naproxen to identify pharmacodynamic biomarkers.

Use of Biomarker Modulation in Normal Mammary Epithelium as a Correlate for Efficacy of Chemopreventive Agents Against Chemically Induced Cancers.

In both estrogen receptor/progesterone receptor-positive (ER/PR) human breast cancer and in ER/PR cancers in the methylnitrosourea (MNU)-induced rat model, short-term modulation of proliferation in early cancers predicts preventive/therapeutic efficacy. We determined the effects of known effective/ineffective chemopreventive agents on proliferative index (PI) in both rat mammary epithelium and small cancers. Female Sprague-Dawley rats were treated with MNU at 50 days of age.

Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers.

Daily dosing of either NSAIDs or EGFR inhibitors has been shown to prevent bladder cancer development in a N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced rat model. However, these inhibitors cause gastrointestinal ulceration and acneiform rash, respectively, limiting their continuous use in a clinical prevention setting. We studied chemopreventive efficacy of pulsatile dosing of EGFR inhibitor erlotinib (42 mg/kg BW, once/week) combined with intermittent or continuous low doses of the NSAID naproxen (30 mg/kg BW/day, 3 weeks on/off or 128 ppm daily in diet) in the OH-BBN induced rat bladder cancer model.

Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers.

Signal transducer and activator of transcription 3 (STAT3) plays a key role in the transformation of normal cells to cancerous cells. Although inhibitors of STAT3 have been shown to suppress the growth of multiple cancer types in vitro and in vivo, such agents are of particular interest for the prevention of breast cancer, which affects over 200,000 women and claims more than 40,000 lives in the United States each year. In the present study, we employed the MMTV/Neu transgenic mouse model, which develops estrogen receptor (ER)‑negative, Neu‑overexpressing tumors, and the Sprague‑Dawley (SD) rat model, which develops ER‑positive tumors upon exposure to the carcinogen 7,12‑dimethylbenz[a]anthracene (DMBA), to test the efficacy of the STAT3 inhibitor GLG‑302 in the prevention of mammary cancer.

[Corrigendum] Daily or weekly dosing with EGFR inhibitors, gefitinib and lapatinib, and AKT inhibitor MK2206 in mammary cancer models.

The AKT inhibitor employed in this article was identified as MK 2206 (8‑[4‑(1‑aminocyclobutyl) phenyl]‑9‑phenyl‑1,2,4‑ triazolo[3,4‑f][1,6]naphthyridin‑3(2H)‑one hydrochloride (1:2). However, another AKT inhibitor was actually used, which is typically identified as Akt I‑1,2 (HC,I. IPA (2‑[4‑(3‑phenylquinoxalin‑2‑yl)phenyl]propan‑2‑amine hydrochloride isopropanol (1:1:1).

Daily or weekly dosing with EGFR inhibitors, gefitinib and lapatinib, and AKt inhibitor MK2206 in mammary cancer models.

Daily vs. weekly dosing with EGFR inhibitors (gefitinib and lapatinib) and an AKT inhibitor (MK2206) were compared in two rodent breast cancer models. Female Sprague-Dawley rats were administered methylnitrosourea (MNU) at 50 days of age, and gefitinib (daily/weekly dosing at 10/70 mg/kg BW) or lapatinib (daily/weekly dosing at 75/525 mg/kg BW) were administered by gavage beginning 5 days after MNU.

α-glucosidase inhibitors isolated from L.

The aim of the study was to isolate digestive enzymes inhibitors from through a bioassay-guided fractionation approach. Repeated silica gel and sephadex LH 20 column chromatographies of bioactive fractions afforded stigmasterol, quercetin and avicularin as digestive enzymes inhibitors whose IC values as compared to acarbose (351.02 ± 1.

Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer.

Metformin is a biguanide employed in treating type II diabetes. Its potential efficacy for treating cancer has been demonstrated epidemiologically (lower cancer incidence in metformin users compared with users of sulfonylureas or insulin) and mechanistically, primarily in cell culture. Metformin decreases the levels of insulin-like growth factor 1 and secondarily inhibits the mammalian target of rapamycin pathway to exhibit anticancer effects.

5MeCDDO Blocks Metabolic Activation but not Progression of Breast, Intestine, and Tongue Cancers. Is Antioxidant Response Element a Prevention Target?

The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.

Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects.

Lack of effect of metformin on mammary carcinogenesis in nondiabetic rat and mouse models.

Epidemiologic studies have shown that diabetics receiving the biguanide metformin, as compared with sulfonylureas or insulin, have a lower incidence of breast cancer. Metformin increases levels of activated AMPK (AMP-activated protein kinase) and decreases circulating IGF-1; encouraging its potential use in both cancer prevention and therapeutic settings. In anticipation of clinical trials in nondiabetic women, the efficacy of metformin in nondiabetic rat and mouse mammary cancer models was evaluated.

Osteopontin facilitates ultraviolet B-induced squamous cell carcinoma development.

Background: Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis.

Objective: To determine whether OPN facilitates the development of cSCC and its function.

Methods: cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks.

Effect of intermittent dosing regimens of erlotinib on methylnitrosourea-induced mammary carcinogenesis.

EGF receptor (EGFR) inhibitors are used in the therapy of lung and pancreatic cancers and effectively prevent cancers in multiple animal models. Although daily dosing with erlotinib is effective, weekly dosing may reduce toxicity and have advantages, particularly for prevention. We tested alternative dosing regimens for preventive/therapeutic efficacy in a rat mammary cancer model.

Chemopreventive efficacy of Targretin in rodent models of urinary bladder, colon/intestine, head and neck and mammary cancers.

The chemopreventive efficacy of Targretin was evaluated in various rodent cancer models. In the rat model of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced urinary bladder cancer, it was found that Targretin administered in the diet (beginning one week after the last OH-BBN treatment) for 5.5 months increased the number and size of urinary bladder cancers.

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: is DIM a substitute for I3C?

The abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis.

Efficacy of the EGFr inhibitor Iressa on development of chemically-induced urinary bladder cancers: dose dependency and modulation of biomarkers.

The effects of the EGFr inhibitor Iressa on development of urinary bladder cancers induced by hydroxybutyl(butyl)nitrosamine (OH-BBN) in rats were examined. Iressa treatment (4.5 or 1.

Screening agents for preventive efficacy in a bladder cancer model: study design, end points, and gefitinib and naproxen efficacy.

Purpose: We optimized agent testing in an in vivo bladder cancer model and determined the most sensitive, relevant protocol to test efficacy in clinical prevention trials.

Materials And Methods: Female Fischer-344 rats (Harlan) were treated with the bladder carcinogen OH-BBN (TCI America, Portland, Oregon) for 8 weeks. Rats were treated with naproxen (400 mg/kg diet), aspirin (Sigma(R)) (300 or 3,000 mg/kg diet), Iressa(R) (10 mg/kg gefitinib body weight daily) or resveratrol (1,000 mg/kg diet) using 1 of 3 protocols, including treatment beginning 1) 1 week after OH-BBN and continuing for 7 months, 2) 3 months after OH-BBN after microscopic lesions already existed and continuing for 3 months, and 3) 1 week after OH-BBN and continuing for 4 months.

Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line.

Osteopontin (OPN) is a secreted glycoprotein implicated to function in cancer development and metastasis. Although elevated expression of OPN are observed in cancer cells of various types, in some cases, only the cells in the stromal region surrounding the tumor express OPN, suggesting distinct functional roles for this protein derived from host cells and from cancer cells. To provide a model for addressing the functions and mechanisms of host-derived OPN in cancer progression and metastasis, a cutaneous squamous cell carcinoma cell line (ONSC) that lacks the OPN gene, Spp1, was established.

Chemopreventive efficacy of naproxen and nitric oxide-naproxen in rodent models of colon, urinary bladder, and mammary cancers.

Nonsteroidal anti-inflammatory drugs (NSAID) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically, and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal ulceration and may increase cardiovascular events. Naproxen seems to cause the lowest cardiovascular events of the common NSAIDs other than aspirin.

Mycoplasma pulmonis and lymphoma in bioassays in rats.

Lymphomas were reported to be induced in rats in bioassays of aspartame, methyl-tertiary-butyl ether (MTBE), and other chemicals conducted by a nonprofit cancer research organization. European regulatory authorities concluded that lymphomas in the aspartame study were caused by Mycoplasma pulmonis and suggested that this also was the case for the MTBE bioassay. To assess the role of M.

Lack of efficacy of the statins atorvastatin and lovastatin in rodent mammary carcinogenesis.

The statins are highly effective in lowering cholesterol by inhibiting 3-hydroxy-3-methylglutaryl CoA reductase. Recently, there has been conflicting epidemiologic data indicating that statins decrease the incidence of certain types of cancer, including breast cancer. Atorvastatin and lovastatin, statins with different lipophicilities, were administered in diet either as single agents or in combination with suboptimal doses of tamoxifen or the retinoid X receptor agonist bexarotene were evaluated for prevention of estrogen receptor-positive mammary cancers induced in the rat with methylnitrosourea.

Rosiglitazone, a PPAR gamma agonist: potent promoter of hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers.

In an initial study to determine if rosiglitazone had chemopreventive activity, Fischer-344 female rats were administered twice weekly doses of hydroxybutyl(butyl)nitrosamine (OH-BBN), a urinary bladder specific carcinogen, for 8 weeks. Two weeks following the last dose of OH-BBN, rats were administered rosiglitazone (50 mg/kg BW) daily by gavage for the remainder of the study (7 months). Only 57% of OH-BBN-treated animals developed palpable urinary bladder cancers during the course of the study, while all of the OH-BBN plus rosiglitazone treated rats developed large cancers (p < 0.

Effect of cranberry juice concentrate on chemically-induced urinary bladder cancers.

The chemopreventive efficacy of cranberry juice concentrate in an experimental model of urinary bladder cancer was evaluated using female Fischer-344 rats. The animals received N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) for a period of eight weeks. Cranberry juice concentrate was administered at doses of 1.