BackgroundObesity is part of the established risk factors for breast cancer (BC) in postmenopausal females. Circulating leptin increases in parallel with the increase of body weight and fat reservoir.MethodsThis research investigated the link between leptin phenotype and the clinicopathological factors in BC. A large set of breast cancer cases (449), and 27 non-cancerous tissue samples of breast were employed for leptin expression recognition using immunohistochemistry staining.ResultsCytoplasmic immunohistochemical staining of leptin was recognized in 376 (83.7%) and 25 (92.6%) of BC and control cases respectively. Leptin immunostaining were significantly associated with age, histotypes, grade, stage, lymph node involvement, tumor recurrence, hormone receptor phenotypes, ER and HER2 expressions, and p-values were (P = 0.0233), (P = 0.0001), (P = 0.050), (P = 0.0291), (P = 0.0300), (P = 0.0023), (P = 0.0021), (P = 0.0279) respectively. Reasonable proportion of cases with low staining score was more prevalent in all subgroups of clinicopathological parameters except ER- PR+ HER2- hormone receptor phenotype and mucinous carcinoma which showed high level of leptin immunoreactivity. Tumor recurrence is less prevailing in high score leptin immunostaining cases. Furthermore, Log Rank (Mantel-Cox) test findings revealed considerably different survival distributions were observed for the different categories of leptin immunostaining scores (P = 0.032). Negative leptin immunostaining is related to poor survival.ConclusionsOur preliminary findings support leptin clinical value in confirming BC diagnosis as well as prognosis. These results suggest that leptin molecule is an important biomarker that could identify type, grade, stage, lymph node involvement, relapse and prognosis in breast cancer.

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IntroductionA controversy regarding the association of Epstein-Barr virus (EBV) with breast carcinomas has recently been reported in the literature. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and breast carcinomas in Jordanian females.Material and methodsExtraction of DNA from the archive samples of breast carcinoma cases embedded in paraffin wax was performed and the extracted DNA was subjected to polymerase chain reaction amplification to detect the EBV genome using four sets of primers for EBER 2, BNLF-1, EBNA 2, and Gp220. Immunohistochemistry study was performed on sections of 4 µm which were cut from paraffin blocks of tumor and control groups. Monoclonal antibody against EBNA-1 was applied to all slides to identify the EBV-infected tumor cells. Detection was performed using the Dako envision dual link system.ResultsDNA was successfully extracted from 92 paraffin embedded samples of breast carcinoma patients, and from 49 normal samples. The extracted DNA was confirmed by using glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) primers. Twenty-four out of 92 breast carcinoma specimens was found to be infected with EBV as compared to 3 out of 49 control group specimens, which represented a statistically significant difference (p-value using χ2 = 0.008). Immunohistochemically, 24 (26%) of the 92 studied samples were found to be positive, showing EBNA-1 granular nuclear staining in tumor epithelial cells.ConclusionsThese findings suggest an association between EBV infection and breast carcinoma development.

Leptin phenotype has been suggested to be a possible biomarker for the diagnosis and prognosis of different neoplasms. Nonetheless, there are conflicts among the outcomes found in several tumors, and little is proven concerning the correlation between the phenotype of leptin and its clinical significance in colorectal carcinomas. This study will describe the phenotype of leptin in colorectal adenocarcinomas, and investigate its correlation with clinicopathological factors.Two hundred and twenty eight tissue samples include 155 colorectal carcinomas, 40 adenomas, and 33 noncancerous cases were utilized in constructing tissue microarrays which have been used in the revealing of leptin expression using leptin monoclonal antibody and immunohistochemistry staining protocol.Immunoexpression of leptin was recognized in 145 (93.5%) of colorectal tumors and 56 (76.7%) cases of control group. Histotype was considerably associated with leptin phenotype (P = .000), there is up regulation in leptin expression in colorectal carcinoma cases. Significantly higher proportion of negative leptin immunostaining cases were observed in tumors which have size more than 5 cm (P = .045). Whereas, significant different survival patterns were observed in positive cases regarding tumor size, lymphovascular invasion, distant metastasis, local recurrence and relapse of disease (P-values .046, .011, .000, .013, and .001, respectively). On the other hand, positive leptin staining colorectal tumors with size <5 cm, and with no distant metastases, local recurrence, or disease relapse had significantly better survival estimates. However, leptin immunostaining did not show noteworthy associations with age, gender, differentiation, tumor location, stage, margins involvement, lymphovascular invasion, and lymph node metastasis.The current study shows up regulation in leptin expression in colorectal adenocarcinoma compared with noncancerous control cases. Thus, immunohistochemical staining of leptin in colorectal cancer could be a helpful tool in the prediction of prognosis and survival pattern of colorectal cancer with certain clinicopathological factors (tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease).

Impact statementRoflumilast, a selective phosphodiesterase-4 inhibitor, was approved for the treatment of chronic obstructive pulmonary disease (COPD). This study showed that co-inhalation of roflumilast and fluticasone significantly decreased airway hyperresponsiveness in ovalumin-asthmatic mice. Also, it more significantly improved inflammation and histopathological changes than co-inhalation of formoterol and fluticasone. The current results showed that inhaled roflumilast reduced counts of eosinophils, neutrophils, and macrophages in bronchoalveolar lavage fluid. Consequently, inhaled roflumilast might be of potential off-label benefit in treatment of eosinophilic and neutrophilic asthma and asthma-COPD overlap syndrome (ACOS). These results could also support other experimental and clinical studies addressing the same issue. AbstractRoflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n ¼ 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (mg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast þ fluticasone (500 þ 1000), and formoterol þ fluticasone (50 þ 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-a, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-a, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast þ fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast þ fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast þ fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol þ f...