Targeting AMPK, mTOR and ß-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and ß-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients. MATERIALS AND METHODS: HepG2 cells were exposed to increasing concentrations of metformin, aspirin and combined treatment, and an MTT assay was performed to determine half maximal inhibitory concentration (IC50). Caspase-3 activity, cell cycle analysis, and protein expression of AMPK, phosphorylated AMPK (pAMPK) and mTOR proteins were assessed. Furthermore, the expression and localization of ß-catenin protein was assessed by immunocytochemistry, and protein expression of pAMPK, mTOR and ß-catenin was assessed in Egyptian HCC and cirrhotic tissue specimens. RESULTS: Metformin/aspirin combined treatment had a synergistic effect on cell cycle arrest at the G2/M phase and apoptosis induction in a caspase-dependent manner via downregulation of pAMPK and mTOR protein expression. Additionally, metformin/aspirin combined treatment enhanced cell-cell membrane localization of ß-catenin expression in HepG2 cells, which might inhibit the metastatic potential of HepG2 cells. In Egyptian HCC specimens, pAMPK, mTOR and ß-catenin proteins showed a significant increased expression compared with cirrhotic controls. CONCLUSIONS: Targeting AMPK, mTOR and ß-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients.

Expression of mesothelioma-related markers in meningiomas: an immunohistochemical study.

BACKGROUND: Meningiomas are common intracranial tumors. Recently, histogenetic and phenotypic similarities between meningiomas and mesotheliomas have been proposed. We were interested in whether these similarities are reflected on the immunohistochemical level, which would add new potentially diagnostic markers for meningiomas. METHODS: The expression of mesothelioma-related markers (D2-40, Calretinin, Keratin 5/6, WT1, and Methotheioma-Ab1) was investigated in 87 cases of meningiomas and compared to EMA expression. RESULTS: 73.6% of meningioma cases were grade I, 20.7% were grade II, and 5.7% were grade III. 83.9% of meningioma cases were classical and 16.1% had special nonmeningothelial features. D2-40 was expressed in 37.9% of cases and was significantly restricted to classical meningiomas. Calretinin and WT1 were negative while Keratin 5/6 and Mesothelioma-Ab1 were weakly expressed in classical variants (5.7% and 3.4%, resp.). EMA was consistently expressed in all cases. Its expression was significantly higher than that of mesothelioma-related markers; this held true also when D2-40 expression was considered separately. CONCLUSIONS: Mesothelioma-related markers are not extensively expressed in meningiomas, a finding that argues against their proposed histogenetic and phenotypic similarities. Compared to EMA, the significantly lower expression of mesothelioma-related markers and their restricted expression to classical meningioma variants hamper their potential future use as diagnostic markers for meningioma.

Pathological, immunohistochemical and microbiologicalal analysis of lacrimal sac biopsies in patients with chronic dacrocystitis.

AIM: To analyze cases of obstruction of the nasolacrimal duct which creates a fertile environment for secondary bacterial infection and can result in dacryocystitis, which is a constant threat to cornea and orbital soft tissue and a potential source of endophthalmitis following intraocular surgery. The majority of obstructions of the lacrimal excretory outflow system are acquired ones occurring in adulthood and involving the distal parts of the system. Acquired obstruction may be primary/idiopathic or secondary to a wide variety of infectious, inflammatory, traumatic, mechanical, toxic or neoplastic causes mimicking idiopathic inflammation. These cases are treated by dacryocystorhinostomy (DCR). METHODS: The present study was conducted to determine the histopathologic, immunohistochemical and current microbiologic characteristics of lacrimal sac specimens in patients undergoing external dacryocystorhinostomy. RESULTS: Non-specific lacrimal sac pathology was present in all 33 cases and 81.8% of the cases showed moderate chronic inflammation with a chronic inflammatory score (CIS) ranging between 4 and 6, whereas 12.12% showed severe inflammatory changes with a CIS of 7. Mild degree of inflammation was seen in 6.06% with a CIS of 3. The total prevalence of gram-positive, gram-negative, and culture-negative samples were 59.4%, 37.5%, and 3% respectively. CONCLUSION: Non-specific chronic inflammation with fibrosis is indeed the most commonly reported histopathological finding in lacrimal sac wall biopsy specimens.