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Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant with the elevated risk of multiple cancerous diseases involving breast carcinoma, but with inconclusive findings. The primary purpose of this study is to test the association of this essential variant with the risk of breast carcinoma among Egyptian females. This case–control study was conducted based on 200 participants involving 100 women diagnosed with breast carcinoma and 100 unrelated cancer-free controls from the same district. The genomic DNA for all participants was genotyped utilizing T-ARMS-PCR procedure. The frequencies of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant indicated a statistically significant with the elevated risk of breast carcinoma under various genetic models, including allelic (OR = 2.48, P-value G) variant was considered as an independent risk factor for breast carcinoma among Egyptian women.

Background: Despite significant advances in therapeutic interventions, liver cancer is the leading cause of cancer mortality in the world. Potential phytochemicals have shown to be promising agents against many life-threatening diseases because of their low toxicity and potential effectiveness. Objective: The current study aims to conduct an in vitro investigation of the anticancer activity of Apricot Extract (AE) and Amygdalin Containing Fraction (ACF), additionally studying their therapeutic effects on DMBAinduced liver carcinogenesis mice model to highlight their related biochemical and molecular mechanisms. Methods and Results: Amygdalin was isolated from the seeds of P. armeniaca L. Male mice received AE or ACF, DMBA, DMBA+AE, DMBA+ACF, and vehicles. The oxidative stress and antioxidant markers, cell proliferation by flow cytometric analysis of Proliferating Cell Nuclear Antigen (PCNA) expression, angiogenesis marker (VEGF), inflammatory marker (TNF-α), apoptotic, anti-apoptotic and autophagy genes expression (caspase-3, Bcl-2, and Beclin-1) were investigated. AE and ACF were found to stimulate the apoptotic process by up-regulating caspase-3 expression and down-regulating Bcl-2 expression. They also reduced VEGF and PCNA levels and increased the antioxidant defense system. Moreover, AE and ACF treatments also inhibited HepG2 and EAC cell proliferation and up-regulated Beclin-1 expression. Conclusion: This study provides evidence that, in DMBA-induced hepatocarcinogenesis, the key proteins involved in the proliferation, angiogenesis, autophagy, and apoptosis are feasible molecular targets for hepatotherapeutic potential using AE and ACF.

BACKGROUND: Hematuria is the most frequent presenting symptom in the vast majority of bladder cancer (BC) patients. The current recommended evaluation of hematuria includes cross sectional imaging and cystoscopy with possible high negative results, expensive costs and substantial patient burden. OBJECTIVES: To validate novel urine-based mRNA-dependant tests; Xpert test and urinary metabolomics assay (CRAT and SLC 25A20genes expression) for BC detection in patients with hematuria. METHODS: Patients presented with hematuria to our tertiary care hospital were evaluated by CT urogram and office white light cystoscopy with subsequent inpatient biopsy for positive findings. Voided precystoscopy urine samples were prospectively collected. Xpert test, assay of targeted urinary metabolomics and cytology, were performed. The tests characteristics presumably were calculated based on the ability to identify BC noninvasively. RESULTS: Between March 2018 and June 2019, 181 patients were included in the final analysis with mean (±SD) age 62 (±10) years with 168 (92.8%) males. Macroscopic hematuria was encountered in 153 (84.5%) patients with irritative bladder symptoms in 48 (26.5%) patients. BC was confirmed by cystoscopy/biopsy in 36 (19.9%) patients. The performance characteristics of Xpert alone (SN: 73%, SP: 83%, NPV: 92%, PPV: 52%) (AUC 0.84, 95% CI 0.75–0.93, p = 0.001), metabolomics assay alone (SN: 89%, SP: 93%, NPV: 97%, PPV: 78%) (AUC 0.91, 95% CI 0.85–0.98, p

Diabetic retinopathy (DR) is one of the most common diabetic complications. Genetic factors play an important role in the development and progression of DR. So, the present study aimed to investigate the association ofThis work is a case-control study in which 550 diabetic patients were enrolled. Among them, 280 diabetics with DR (120 T1DM and 160 with T2DM) and 270 diabetic patients without DR (120 T1DM and 150 with T2DM). Besides, 120 healthy subjects as a control group. Genotyping ofC allele and CC genotype ofThe present study revealed the association of

Hepatocellular carcinoma (HCC) is a lethal disease, and in HCC advanced stages, there is limited therapeutic efficacy. HCC results in a complication of fibrosis or cirrhosis. In this study, the protective effect of curcumin and selenium versus hepatocellular carcinoma caused by CCl4 in experimental animals was investigated. In all, 70 mice were divided into seven groups to study the effect of curcumin and selenium on CCl4 -induced hepatocellular carcinoma. After treatment time, different animal groups were sacrificed, serum and liver samples were collected and processed for assay of biochemical and molecular parameters. Our results showed that CCl4 administration induced various alterations such as significant elevation in the serum levels of ALT, AST, and hepatic contents of malondialdehyde (MDA), and depletion in the levels of antioxidant parameters. CCl4 induced apoptosis in the hepatic cells indicated by an increased level of p53, CD4, CD8, Bax, and Annexin V/PI in addition to significant decrease in the level of Bcl-2. Administration of curcumin and selenium restored this abnormal variation in these biochemical parameters to normal values. Our study addressed that curcumin or selenium may be helpful in the protection against liver damage induced by CCl4 . The hepatoprotective impact of curcumin or selenium might be mediated primarily by its potent antioxidant activity. PRACTICAL APPLICATIONS: Hepatocellular carcinoma (HCC) ranked third common cause of death, primary liver cancer. Exposure to CCl4 was found to induce significant hepatotoxicity, characterized by fibrosis, bile duct proliferation, cirrhosis, and reduced hepatic function The work was prepared to investigate the protecting capacity of curcumin, selenium alone, and in combination against HCC induced by CCl4 in the experimental animal model. This study proved the protective effect of curcumin and selenium, alone and in combination with each other, where curcumin showed multiple pharmacological activities, including anti-inflammation and antioxidant, and have an essential role in inhibiting the progression of HCC.

Background: Adiponectin gene polymorphisms have recently been reported to be associated with obesity. In Egypt, obesity has expanded especially with the changing nourishment propensities and the inexorably inactive ways of life, with almost 70 percent of the Egyptian populations being obese. Aim: To assess the relationship of the adiponectin gene (ADIPOQ) polymorphism in patients with Obesity in Egyptians. Subjects and methods: This study included 100 patients with obesity and 97 random controls. Results: Adiponectin rs1501299 polymorphism showed significant difference cases with different obesity grades where the T/T genotype was relatively higher in higher classes of obesity (Class II and III; (66.7% and 55.6% respectively, p = 000), which determines the susceptibility to obesity. Conclusion: Adiponectin rs1501299 polymorphism might be a candidate gene, which determines the susceptibility to obesity. Larger studies are necessary to confirm these findings in various populations.

Objective to assess expression of p27 and survivin in chronic gastritis with/without H. pylori ± intestinal metaplasia (IM) and in intestinal-type gastric cancer (IGC). Materials and methods Immunohistochemical staining for p27 and survivin on paraffin-embedded sections of 20 chronic gastritis, 20 H. pylori gastritis, 15 H. pylori gastritis with IM, 50 IGC, and 10 controls. Positivity (number of positive cases) and expression (mean percentage of positive gastric cells) for both proteins were evaluated. Results P27 positivity and expression decreased from control to chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM. In IGC, p27 positivity and expression were lower than controls and chronic gastritis but higher than H. pylori gastritis ±IM. High grade and advanced stage IGCs have insignificantly lower p27 positivity and expression than low grade and early stage IGCs. By contrast, survivin positivity and expression increased from chronic gastritis to H. pylori gastritis to H. pylori gastritis with IM to IGCs. High grade and advanced stage IGCs have significantly higher survivin positivity and expression than low grade and early stage IGCs. Males have higher positivity and expression for p27 and survivin than females. Conclusion Inverse relation between p27 and survivin in H. pylori gastritis, H. pylori gastritis with IM and IGCs lesions, suggesting that both proteins could be used as potential prognostic and/or diagnostic biomarkers in H. pylori and IM associated- gastritis as well as in IGC.

BACKGROUND: Worldwide gastric cancer (GC) ranks sixth in incidence and second in mortality among all malignancies. CDX2 has an essential role in the development and maintenance of intestinal differentiation in the gut and ectopic sites such as intestinal metaplasia (IM) of the stomach. SOX2 contributes to the cell lineages normally found in the stomach, suggesting contribution in gastric differentiation. AIM: The aim of the study was to assess the expression of CDX2 and SOX2 in chronic gastritis (CG) lesions associated with Helicobacter pylori, IM, or dysplasia as well as in intestinal-type GC. METHODS: Immunohistochemical staining for CDX2 and SOX2 were applied on archival paraffin blocks from 80 CG cases, 40 intestinal-type GC cases, and 10 controls. CG cases were either of non-specific inflammation or associated with H. pylori infection. GC cases were of intestinal-type only, excluding any other type of GC. Control cases were of minimal gastritis, negative for H. pylori, IM, and dysplasia. RESULTS: CDX2 expression was correlated with CG associated with H. pylori, IM, and dysplasia as well as with more differentiated and less invasive pattern of intestinal-type GC, while SOX2 expression was correlated with CG negative for H. pylori and IM as well as with less differentiated and more invasive intestinal-type GC. CONCLUSION: Both CDX2 and SOX2 could predict the behavior of CG disease over time and plan the suitable line of treatment and both proteins could be potential targets for novel therapeutic interventions.

Background Hepatocellular carcinoma (HCC) is the second most common cancer-related death in the world. No effective curative option exists for the treatment of HCC. The available drugs exhibit severe toxic effects and low therapeutic index. Aim This work aimed to examine different monocationic arylthiophene derivatives for possible use as chemotherapeutic agents against HCC. Methods The IC50 values for the compounds were determined. The mechanism of cytotoxicity was further investigated using different methods. Results Compound 2j proved to retain the highest cytotoxicity in comparison to as a positive control. The selectivity index of compound 2j revealed the safety to normal cells. Moreover, compound 2j was able to inhibit HepG2 cells´ migration and division. The anticancer effect of compound 2j was found to be partially via cell cycle arrest, activation of the tumour suppressor p53 protein, and induction of apoptosis via both intrinsic and extrinsic pathways. Compound 2j has a potential sensitization activity and significantly reduced the IC50 values for the anticancer drugs doxorubicin, cisplatin, and taxol. Conclusion The tested arylthiophenes showed a potent cytotoxicity against HepG2 cells and were safe to normal cells. The most active compound 2j was found to be able to inhibit cell division and migration and also to induce apoptosis. Compound 2j also proved to have a sensitization effect on standard anticancer drugs.

Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.

Background Colorectal cancer (CRC) is the fourth most common cancer worldwide. Both HER2 and SKP2 have a carcinogenic role in CRC making them attractive targets for tailored treatment. This work aims to correlate HER2 and SKP2 protein expression as well as HER2 gene amplification with clinicopathological parameters aiming at identifying potential candidates for targeted therapy. Methods This Study was conducted on 127 paraffin-embedded tissue samples of different colorectal lesions [controls, chronic colitis, ulcerative colitis (UC), hyperplastic polyps (HPs), adenomas and CRCs] to investigate HER2 and SKP2 expression by immunohistochemistry (IHC), Selected CRC cases [equivocal (2+) and positive (3+) by IHC] were further evaluated by ISH (CISH and SISH ) to assess HER2 gene amplification. Results Chronic colitis, UC, HPs and adenomas were HER2-negative. HER2 positivity (scores 2+ and 3+) was found only in15% of CRCs. Both SISH and CISH showed the same results with high concordance as 66.7% of equivocal and 100% of positive cases showed amplification of HER2 gene. SKP2 positivity was detected in 26.7% and 45% of adenomas and CRCs respectively, while other studied groups were negative. A significant correlation was noted between HER2 and SKP2 expression. Conclusion A small percent of CRCs exhibited HER2 gene amplification, which would be potential candidates for anti HER2 therapy whereas IHC could be a primary screening test for patient selection. A potential carcinogenic role of SKP2 was suggested by the findings that SKP2 expression was undetectable in normal colonic mucosa but significantly increases from adenoma to carcinoma, hoping adenoma patients to get benefit from targeted therapy. .

AIMS: Diabetes mellitus and diabetic retinopathy (DR) are major public health concerns globally. Oxidative stress plays a central role in the pathogenesis of diabetes and DR. The aim of this study was to investigate the association of malondialdehyde, uric acid and bilirubin with diabetes and diabetic retinopathy development. METHODS: This study was conducted on 110 diabetics (with and without retinopathy). Beside 40 healthy individuals as a control group. The level of three markers (malondialdehyde, uric acid and bilirubin) was estimated in the studied groups. Receiver operating characteristic analysis and a logistic regression model was performed. RESULTS: The present study revealed significantly higher uric acid and malondialdehyde levels, while bilirubin showed significantly lower levels in diabetics compared to control and similarly in diabetic retinopathy compared to those without DR. Furthermore, combination of the three markers increased the accuracy and effect size for differentiation between diabetes with and without DR. In addition, higher levels of uric acid and malondialdehyde were associated with risk of diabetes and DR development. CONCLUSION: This study concluded that higher levels of uric acid and malondialdehyde were associated with increase in the risk of diabetes and DR development, while bilirubin wasn’t associated with decreasing the risk of diabetes or DR. However, the combination of malondialdehyde, uric acid and bilirubin may be a valuable addition to the current options for the prognosis of DR. In addition, malondialdehyde may be independent predictor of diabetes and DR as well as uric acid may be used as independent biomarker to predict the risk of DR.

BACKGROUND Polymorphisms of certain genes may have an effect on either persistence of infection or spontaneous clearance of hepatitis C virus (HCV). We hypothesized that one or more variants of chemokines (CCL2 and CCL5) and chemokine receptors (CC chemokine receptor type 2 [CCR2]) genes are associated with the susceptibility to HCV infection. METHODS We recruited 1460 patients with chronic HCV (CHC), 108 subjects with spontaneous virus clearance (SVC) and 1446 individuals as a healthy control group. All were genotyped for single nucleotide polymorphisms: rs13900 C/T of CCL2, rs3817655 T/A of CCL5 and rs743660 G/A and rs1799864 G/A of CCR2 using allelic discrimination real-time PCR technique. RESULTS The carriage of the A allele of CCR2 rs743660 was significantly higher in CHC compared to SVC (odds ratio [OR] 4.03) and to controls (1.42) and in controls compared to SVC (2.85) (all P

Background: In some genes, Polymorphisms may have an influence on the persistence of HCV infection, HCV replication, or spontaneous clearance of the virus. This study was carried out to investigate the association of chemokines CCL2 gene polymorphism with the susceptibility to HCV infection with high-resolution techniques in Egyptian families. Methods: A total of 75 Egyptian families with a total of 291 subjects in this study were recruited from different Egyptian populations from Dakahlia governorate and were classified into 2 groups: 146 infected persons with chronic hepatitis C (CHC), 145 subjects as a healthy control group. All subjects were genotyped for rs13900 C/T SNP of CCL2 gene using allelic discrimination real time PCR (RT-PCR) technique. Results: The allele carriage of at least one copy of C allele of CCL2 rs13900 C/T polymorphism was significantly lower in the positive group when compared to that of negative group (OR = 0.4169, 95% CI 0.1830 to 0.9496, p 0.0372) indicating that The C allele of rs13900 C/T polymorphism is protective allele against development of chronic HCV while the allele carriage of homozygotes TT of CCL2 rs13900 C/T polymorphism was significantly higher in the positive group when compared to that of negative group (OR = 2.3986, 95% CI 1.0530 to 5.4635, p 0.0372) indicating that The C allele of rs13900 C/T polymorphism is protective allele against development of chronic HCV. Conclusions: HCV infection is associated with rs13900 C/T SNP of CCL2 gene in the Egyptian families.

Two series of fused tricyclic sultams (carboxylates, 3a, b and 5a, f, g and anilides 5b-e) were synthesized from saccharin and their chemical structures were confirmed by spectroscopic tools. Then, their antibacterial activities and MIC were evaluated against two strains of gram positive and gram-negative bacteria. The MIC values of the tested compounds are in the of range 8–33 μg/ml. In addition, their DNA cleavage ability, binding affinity and their anticancer activities against hepatic cancer cell were tested. And their antioxidant activities were also measured. Four carboxylate derivatives ( 3a, 5a, 5f and 5g) and one anilide ( 5d ) of the tested compounds proved to be the highest activity all over the study.

Eleven compounds of substituted 4-(5-arylthiophen-2-yl)benzamidines 4a-k were synthesized from their corresponding mononitriles via treatment with lithium trimethylsilylamide and subsequent de-protection with ethanol/hydrogen chloride. In vitro antiproliferative activities of the new monocationic arylthiophenes were evaluated against 60 human cell lines at NCI, USA. This class of compounds displayed promising submicromolar antiproliferative activities with the most potent compound being 4i (GI50 and TGI of 0.20 and 0.37 μM, respectively). On the other hand, most of the tested compounds exhibited LC50 at concentrations much higher than those they had GI50 at; ∼10× (for 4b) up to 228× (for 4e) which indicates lower lethality and efficient growth inhibition. Cancer cell lines, HCC-2998 colon, SNB-75 CNS, MDA-MB-435 melanoma, and MCF-7 breast cancer were the most responsive, with GI50s of 0.156, 0.165, 0.163, and 0.168 μM, respectively. The p-chlorophenyl derivatives 4e and 4i discerned themselves with GI50 values at 0.36 and 0.20 μM, respectively, and LC50 values at ∼83 and 36 μM, respectively, but safe to RBCs at 1000 μM. The cytotoxic activity data of these compounds in two normal cell lines; WI38 and WISH proved that they are very safe on normal cells. The plausible mechanism of action of the tested monocations was examined by evaluating their antioxidant power, nuclease-like DNA degradation aptitude and tyrosine kinase (TK) inhibition activities. The tested monocations showed potent activity in all assays. Compounds 4e and 4i caused 88 and 98%, respectively, inhibition in TK activity at 1 μM and the IC50 for 4i was 13 nM. The tested monocations have selective anticancer activity without insulting normal cells most probably due to inhibition of the key enzyme TK at nanomolar concentrations.

Older adults are mostly affected by chronic lymphocytic leukemia (CLL). The present study aimed to evaluate oxidative stress in CLL and to assess its impact on IL-9, Th9 cells levels and prognosis of cases. Seventy Egyptian CLL patients and 15 healthy controls were included. Th9 cell and immunophenotyping of abnormal B cells were assessed by flow cytometry, IL-9 level using ELISA, IL-9 mRNA by qRT-PCR, cytogenetics using FISH, and oxidative stress parameters were determined spectrophotometrically and with native gel electrophoresis. Oxidative stress was elevated in CLL that correlated with abnormal immunophenotyping, cytogenetic changes, bad prognosis, Th9 cells, and overexpression of IL-9. Levels of IL-9 and Th9 cells were strongly correlated with oxidative stress and bad prognostic markers in CLL, indicating that these cells may contribute to CLL by novel mechanisms that could include oxidant injury.

Background: Liver cancer is a life threating disease as it is the fifth most common cancer and the third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment. Methods: This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 μM of each compound, cell viability was determined. Results: The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-β-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 μM, respectively. Both the compounds showed higher selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA which might be attributed to its higher activity and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation. Conclusion: This work highlights the cytotoxicity of glycyrrhizin and its derivatives for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18β-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer.

Introduction DR is the most severe and sight-threatening diabetic microvascular complication. DR is the main cause of blindness worldwide. Genetic factors play an important role in the development of DR. Therefore, the present study aimed to investigate the association of aldose reductase (AR) C106T (rs759853) gene polymorphism with the risk of DR in type 2 DM (T2DM) in the Egyptian population. Methods This study was performed on 280 subjects, including 120 T2DM without DR and 160 T2DM with DR patients. DNA was extracted from the whole blood and the genotyping of the rs759853 was determined, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Genotype frequencies of the rs759853 polymorphism were consistent with Hardy–Weinberg equilibrium (HWE). Genotype frequencies were 55.0%, 37.5% and 7.5% for CC, CT and TT; respectively in T2DM with DR group. While the frequencies in T2DM without DR 46.7%, 40% and 13.3% for CC, CT and TT; respectively. Multiplicative, dominant and recessive models showed no significant associations between C106T (rs759853) studied SNPs and development of DR within T2DM. There were no significant differences in creatinine, FBG and HbA1c concentrations between genotypes of AR in T2DM groups (with and without DR) (P > 0.05 for each). In T2DM without DR, there were significant different between level of total cholesterol and AR genotype. Logistic analysis confirmed that HbA1c and duration of diabetes were associated with the risk of DR, while AR (rs759853) had no significant role in development of DR. Conclusion The present study investigated the association of HbA1c and duration of diabetes with development of DR, while excluded the role of C106T rs759853 polymorphism in conferring risk of DR. Furthermore, this polymorphism was not independent genetic risk factors for DR in Egyptian population. However, other SNPs within this gene might influence the risk of DR. So future genotyping of other functional variants within this gene are necessary to unravel the role of aldose reductase in DR.

Small heterocyclic compounds containing nitrogen and sulfur atoms, such as thiazole derivatives, represent a significant class of organic azoles that exhibit promising bioactivities and have a great potential in medicinal and agricultural fields. A convenient and high-yielding synthetic approach for a range of organic molecules is presented. The nuclease-like activities of compounds were studied with the aid of E. coli AB1157 DNA and agarose gel electrophoresis. The antioxidant evaluation of the compounds was carried out with different antioxidant techniques, such as ABTS and NO scavenging efficiency. The antibacterial behavior was evaluated against various bacterial strains, both Gram-positive and -negative, and the minimum inhibitory concentration (MIC) values of these compounds were determined. The antiproliferative activities and IC50 values of the synthesized organic molecules compounds against HEPG-2, MCF-7, and HCT-116 cell lines were evaluated.

Objective: The aim of this study was to estimate some tumor markers such as caspase-3, caspase-8 and annexin-v levels in blood and tissue of patients with breast cancer and establishing the relation between these apoptotic markers level and response to chemotherapy. Materials and Methods: A number of 150 females were divided into four groups, malignant neoplasm of breast cancer included 50 females, that were diagnosed into stage I, II, III, and IV and included inflammatory breast carcinoma, infiltrating ductal carcinoma, infiltrating lobular carcinoma, ductal carcinoma in situ and lobular carcinoma in situ, control group included 50 females with normal breast, benign neoplasm of breast cancer included 25 cases that contained a heterogeneous group of lesions including developmental abnormalities, epithelial and stromal proliferations and neoplasms and follow up group (after chemotherapy) include 25 cases that her surgery was done and taken chemotherapy. Flow cytometry was used to analyze cell cycle, caspase-3, caspase-8 and annexin-v among the study groups. Results: The results showed that caspase 3 and caspases-8 expressions were significantly decreased in malignant group compared with the control group (P = 0.0028 and P =0.008), respectively; caspase 3 and caspase-8 levels decreased significantly in malignant group compared with the follow up group (P =0.001and P =0.0105), respectively; caspase 3 and caspases-8 levels were decreased in benign group compared with the control group (P = 0.041and P =0.512). Annexin-v was highly expressed in both tissues and blood of malignant groups in viable stage than benign compared with the normal groups (P = 0.01 and P = 0.006) respectively. Annexin-v level was highly expressed in both tissues and blood of malignant groups in necrotic stage compared with the control and follow up groups (P = 0.0001 and P = 0.01). But in early and late apoptotic phase follow up group annexin-v level was significantly increased more than the malignant group with (P=0.0001 and P=0.0026) respectively. Sub G1 apoptosis level in malignant and benign group significantly decreased compared with the follow up group (P = 0.0001 and P = 0.003) respectively. Our data showed that S phase level was significantly increased among malignant group compared with the control and follow up groups (P = 0.0001), also S phase level was increased significantly among benign group more than the control and follow up groups (P= 0.9 and P=0.003) respectively; and S phase was significantly decreased in benign group compared with the malignant blood and tissue groups (P = 0.03 and P=0.05) respectively. Conclusion: Annexin-v, caspase-3 and caspase-8 level in blood and tissue may serve as markers for the diagnosis of breast cancer and the response to chemotherapy. Also, S phase of cell cycle is one of the significant factors in the development of breast cancer.

Tenoxicam and lornoxicam are nonsteroidal anti-inflammatory drugs, were subjected to photoirradiation at 254 nm led to the photodegradation of the pharmaceutical agents. Both, the isolated photodegradation products and the pharmaceutical agents were examined toward DNA binding and degradation. The photodegradation products degrade calf thymus in concentration dependent manner.

The proteins of SMC family are characterized by having Walker A and B sites. The Escherichia coli RecN protein is a prokaryotic member of SMC family that involved in the induced excision of Tn10 and the repair of the DNA double strand breaks. In this work, the Walker A nucleotide binding site of the E. coli RecN protein was mutated by changing the highly conserved lysine residue 35 to the aspartic acid (D), designated as recNK35D. Reverse genetics was utilized to delete the entire recN gene (ΔrecN108) or introduce the recNK35D gene into the E. coli chromosomal DNA. The recNK35D cells showed decrease in the frequency of excision of Tn10 from gal76::Tn10 after treatment with mitomycin C compared to recN+ cells. The ΔrecN108 cells showed an un-induced increase in the frequency of Tn10 excision from gal76::Tn10 in rec+ background while, recBC sbcBC ΔrecN108 cells are completely deficient in Tn10 excision. The recombination proficiency is reduced in cells carrying recBC sbcBC cells in addition recNK35D mutation. We observed that the Walker A nucleotide binding site is important for the RecN protein. Strains that deleted recN gene are recombination deficient and more sensitive to mitomycin C than strains carrying recNK35D.

Chitosan nanocapsules containing naproxen as an active ingredient were synthesized by ionic gelation method in presence of polyanion tripolyphosphate as a crosslinker. The morphology and diameter of the prepared chitosan nanoparticles was characterized using scanning electron microscopy and transition electron microscopy. Different factors affecting on the size diameter of chitosan nanoparticles such as stirring time and temperature, pH values as well as chitosan concentration were studied. Different factors affecting on the immobilization of naproxen into chitosan nanoparticles such as time, temperature and pH values were optimized. Synthesized naproxen/chitosan nanocapsules were assessed against both Gram positive bacterial strain such as Bacillus subtilis and Staphylococcus aureus and Gram negative bacterial strain such as Pseudomonas aeruginosa and Escherichia coli. Also, the antifungal activity of the naproxen/chitosan nanocapsules against Saccharomyces cerevisiae was demonstrated. Super oxide dismutase like activity of naproxen/chitosan nanocapsules will be determined.

Background: Breast cancer remains the most potent threat to women’s life worldwide. So far, no ideal drug for treatment of breast cancer, all available drugs exhibit severe side effects, poor therapeutic index, and high cost. Objective: Therefore, this study aimed to investigate the potential use of the natural pentacyclic triterpenoids such as Boswellic, Betulinic (BA), Urosolic, Oleanolic acids, Glycyrrhizin and their derivatives for treatment of breast cancer. Materials and methods: The cell viability was firstly determined after treatment with 50 µM of each compound. The effect of the treatment on cell cycle, apoptosis, cell migration and colony formation was evaluated. The ability of the new glycyrrhizin derivative to activate p53 was investigated by flow cytometry. Results: The cytotoxicity assay revealed that glycyrrhizin derivative AM-GA (3-acetyl-18β-glycyrrhetinic-30-methyl ester) and BA were the most cytotoxic against breast cancer cell line MCF-7 with IC50 values 4.5±0.1 and 4±0.1 µM, respectively. Both AM-GA and BA were selective towards breast cancer cells rather than the normal lung fibroblast cell line WI-38. Both AM-GA and BA were able to inhibit the cancer cell migration in the wound healing assay and inhibited colony formation. Studying the mechanism of action revealed that AM-GA inhibited the growth of the breast cancer cells via cell cycle arrest at sub-G1 phase, induction of apoptosis and activation of the tumor suppressor protein p53. Conclusion: This work highlights the unique role of AM-GA against breast cancer via different mechanisms and will be the gate for new potent analogues and fights different cancer types.

A series of bichalcophene monoamidines 4a–f were synthesized from the corresponding mononitriles 3a–f via a direct reaction with LiN(TMS)2 followed by deprotection with ethanolic HCl (gas). Bichalcophene mononitriles 3a–f were synthesized via palladium-catalyzed coupling reactions. Thus, a Stille coupling reaction was performed to prepare 6-[5-(thiophen-2-yl)furan-2-yl]nicotinonitrile (3e), when 6-(5-bromofuran-2-yl)nicotinonitrile was allowed to react with 2-n-tributyltin thiophene. The tested bichalcophenes showed a wide range of DNA and protein degradation effect as judged from agarose gel and SDS-PAGE, respectively. Bichalcophenes 3a–f and 4a–f have broad-spectrum antibacterial efficacy being highly active against both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, and Escherichia coli) bacterial strains. The antifungal activity of these bichalcophene series against Saccharomyces cerevisiae was demonstrated. The MIC of bichalcophenes 3a–f and 4a–f against various microorganisms was also determined. The tested bichalcophenes mimic SOD like activity and inhibited the superoxide radical generation.

INTRODUCTION α-Smooth muscle actin (α-SMA)-positive hepatic stellate cells (HSCs) are pericytes responsible for fibrosis in chronic liver injury. The glial fibrillary acidic protein (GFAP), commonly expressed by astrocytes in the central nervous system, is expressed in vivo in the liver in a subpopulation of quiescent stellate cells. The reports concerning GFAP expression in human liver are still conflicting. The aim of the study is investigation the utility of GFAP compared to α-SMA as an indicator of early activated HSCs, in predicting fibrosis in chronic hepatitis C (CHC) patients. MATERIAL AND METHODS With immunohistochemistry and a semi-quantitative scoring system, the expressions of α-SMA and GFAP on HSCs in liver biopsies from patients with pure CHC (n = 34), hepatitis C virus-induced cirrhosis (n = 24), mixed CHC/schistosomiasis (n = 11) and normal controls (n = 10) were analysed. RESULTS The immunoreactivity of α-SMA and GFAP in perisinusoidal, periportal and pericentral areas was assessed. α-Smooth muscle actin and GFAP-positive HSCs were significantly increased in all diseased groups compared with normal controls. In pure CHC with or without cirrhosis, perisinusoidal α-SMA-positive HSCs were predominant in relation to GFAP-positive cells. On the other hand, GFAP-positive cells were predominant in the group of schistosomiasis as compared with the other diseased groups. It was noticed that expression of GFAP on perisinusoidal HSCs in CHC patients sequentially decreased with the progression of fibrosis. CONCLUSIONS Glial fibrillary acidic protein could represent a more useful marker than α-SMA of early activation of HSCs in CHC patients and seems to be an early indicator of hepatic fibrogenesis.

An expedient synthesis of novel triazoles, tetrazine and thiadiazoles, using conveniently accessible and commercially available starting materials has been achieved. The synthesized compounds were characterized by spectroscopic and elemental analyses, and screened for their antibacterial activities against four different strains, namely E. coli, P. aeruginosa, S. aureus and B. megaterium. In particular, the compounds 5, 24 and 26h exhibited excellent antibacterial activities compared to the reference antibiotic. To get further insight about their behavior, these compounds were tested for their antioxidant activities via SOD-like activity, DPPH free radical scavenging activity, ABST and NO, which showed promising results. Furthermore, these compounds effectively promoted the cleavage of genomic DNA as well, in the absence of any external additives.

Mohamed A Ismail,1,2 Reem K Arafa,3 Magdy M Youssef,1,2 Wael M El-Sayed1,4 1Departments of Chemistry and Biological Sciences, College of Science, King Faisal University, Hofuf, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia, Cairo, Egypt Abstract: A series of 15 monocationic bithiophenes and isosteres were prepared and subjected to in vitro antiproliferative screening using the full National Cancer Institute (NCI)-60 cell line panel, representing nine types of cancer. Among the nine types of cancer involved in a five-dose screen, non-small cell lung and breast cancer cell lines were the most responsive to the antiproliferative effect of the tested compounds, especially cell lines A549/ATCC, NCI-H322M, and NCI-H460, whereas compounds 1a, 1c, 1d, and 7 exhibited potent activity, with GI50 values (drug concentration that causes 50% inhibition of cell growth) from less than 10 nM to 102 nM. In addition, compounds 1c and 1d gave GI50 values of 73 nM and 79 nM, respectively, against the MDA-MB-468 breast cancer cell line. Structure–activity relationship findings indicated that the mononitriles were far less active than their corresponding monoamidines and, within the amidines series, the bioisosteric replacement of a thiophene ring by a furan led to a reduction in antiproliferative activity. Also, molecular manipulations, involving substitution on the phenyl ring, or its replacement by a pyridyl, or alteration of the position of the amidine group, led to significant alteration in antiproliferative activity. On the other hand, DNA studies demonstrated that these monoamidine bichalcophenes have promising ability to cleave the genomic DNA. These monoamidines show a wide range of DNA affinities, as judged from their DNA cleavage effect, which are remarkably sensitive to all kinds of structural modifications. Finally, the novel bichalcophenes were tested for their antioxidant property by the ABTS (2,2'-azino- bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt) assay, as well as lipid and nitric oxide scavenging techniques, and were found to exhibit good-to-potent antioxidant abilities. Keywords: bithiophenes, anticancer, DNA cleavage, antioxidant, Suzuki coupling, Stille coupling

Magdy M Youssef,1,2 Reem K Arafa,3,4 Mohamed A Ismail1,21Department of Chemistry, College of Science, King Faisal University, Hofuf, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 4Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo, EgyptAbstract: This research work deals with the design and synthesis of a series of substituted phenylfuranylnicotinamidines 4a–i. Facile preparation of the target compounds was achieved by Suzuki coupling-based synthesis of the nitrile precursors 3a–i, followed by their conversion to the corresponding nicotinamidines 4a–i utilizing LiN(TMS)2. The antimicrobial activities of the newly synthesized nicotinamidine derivatives were evaluated against the Gram-negative bacterial strains Escherichia coli and Pseudomonas aeruginosa as well as the Gram-positive bacterial strains Staphylococcus aureus and Bacillus megaterium. The minimum inhibitory concentration values of nicotinamidines against all tested microorganisms were in the range of 10–20 µM. In specific, compounds 4a and 4b showed excellent minimum inhibitory concentration values of 10 µM against Staphylococcus aureus bacterial strain and were similar to ampicillin as an antibacterial reference. On the other hand, selected nicotinamidine derivatives were biologically screened for their cytotoxic activities against a panel of 60 cell lines representing nine types of human cancer at a single high dose at National Cancer Institute, Bethesda, MD, USA. Nicotinamidines showing promising activities were further assessed in a five-dose screening assay to determine their compound concentration causing 50% growth inhibition of tested cell (GI50), compound concentration causing 100% growth inhibition of tested cell (TGI), and compound concentration causing 50% lethality of tested cell (LC50) values. Structure-activity relationship studies demonstrated that the activity of members of this series can be modulated from cytostatic to cytotoxic based on the substitution pattern/nature on the terminal phenyl ring. The most active compound was found to be 4e displaying a submicromolar GI50 value of 0.83 µM, with TGI and LC50 values of 2.51 and 100 µM, respectively. Finally, the possible underlying mechanism of action of this series of compounds was investigated by determining their nuclease-like DNA degradation ability in addition to their antioxidant power and all monocations proved to be effective in all assays.Keywords: substituted phenylfuranylnicotinamidines, Suzuki coupling, antiproliferative, antibacterial, antioxidant