Amira Kamal El-Hawary

First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection.

Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.

Molecular subtypes of breast carcinoma in Egyptian women: clinicopathological features.

Breast carcinoma may be classified into distinct molecular subtypes based on immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors. The aim of the study was to identify the clinicopathological features of the molecular subtypes of breast carcinoma in our locality. A total of 274 surgically resected breast carcinomas were selected from the files of the Dr. KRZ referral pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura University. Molecular subtypes were classified into luminal A, luminal B, Her-2/neu-expressing and triple-negative. Clinicopathological and histological features of molecular subtypes were analyzed. Luminal A subtype was the most prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2-expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest histological type was infiltrating duct carcinoma (83.2%), followed by infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal A subtype was significantly correlated to low tumor grade, lower number of positive lymph nodes metastasis, absence of both necrosis and syncytial growth pattern. We concluded that the commonest molecular subtype of invasive breast carcinoma among Egyptian women is luminal subtype A, which displayed favorable features. Triple-negative subtype and medullary carcinomas are present in a ratio higher than in western countries.

An inexpensive method of small paraffin tissue microarrays using mechanical pencil tips

BackgroundTissue microarray technology has provided a high throughput means of evaluating potential biomarkers in archival pathological specimens. This study was carried out in order to produce tissue microarray blocks using mechanical pencil tips without high cost.MethodConventional mechanical pencil tips (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax cylinders from the recipient block, creating from 36 to 72 holes. Three cores of tumor areas were punched out manually by using the mechanical pencil tips from donor paraffin embedded tissue blocks and transferred to the holes of the paraffin tissue microarrays.ResultsThis technique was easy and caused little damage to the donor blocks. We successfully performed H&E slides and immunodetection without substantial tissue cylinder loss.ConclusionOur mechanical pencil tip technique is the most inexpensive easy technique among the literature. It also takes a reasonable amount of time and reduces antibody consumption during immunohistochemistry

Clinical relevance of serum vascular endothelial growth factor and Interleukin-6 in patients with colorectal cancer

Background/Aim: Some biological factors play a role in stimulation of malignant growth, metastasis and angiogenesis; however, their clinical relevance has not yet been well established for most of them. This work was aimed at studying the clinical relevance of serum vascular endothelial growth factor (VEGF) and interleukin -6 (IL-6), in patients with colorectal cancer (CRC). Materials and Methods: Preoperative serum levels of VEGF and IL-6 were measured by enzyme -linked immuno -assay in 35 CRC patients and in 30 healthy controls. Results: CRC patients with or without metastasis had significantly higher VEGF and IL-6 levels than healthy controls (all P < 0.001). Patients with advanced clinical stage had significantly higher levels of VEGF and IL-6 than those with early clinical stage (all P < 0.001). Also, patients with metastatic disease had significantly higher VEGF and IL-6 levels than those with localized disease (all P < 0.001). The diagnostic accuracy for invasiveness was 83% for VEGF (cut off value = 240 pg/ml) and 66% for IL-6 (cut off value = 6.7 pg/ml), with sensitivity 79% and 74% and specificity 68% and 59%, respectively. Conclusion: In CRC patients, preoperative measurement of serum VEGF and Il-6 may prove useful non-invasive diagnostic indicators associated with advanced clinical stage and tumor metastasis that warrants further investigations.

Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas☆

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.

Right hepatectomy for combined primary neuroendocrine and hepatocellular carcinoma. A case report

INTRODUCTION Cases of primary neuroendocrine tumors in the liver combined with hepatocellular carcinoma are scarce. Such cases could present either as combined-type tumor or collision type. PRESENTATION OF CASE A 51-year-old man presented with a mass in the right hemiliver. Serum level of alpha-fetoprotein was slightly elevated (2.3 ng/ml), with normal CA19-9 and CA125. The patient underwent right hepatectomy. The resected specimen showed a well-defined and heterogeneous gray-white to brown friable tumor, 20 cm in diameter. Microscopically, the tumor consisted predominantly of monotonous small- to medium-sized neoplastic cells arranged in trabeculea separated by sinusoidal spaces. Immunohistochemically, the tumor cells were strongly positive for synaptophysin and focally positive for chromogranin-A. Interestingly, the tumor cells showed patchy positive coarse granular staining of HerPar-1 involving about 1% of the tumor cells. Glypican-3 staining was negative. These immunohistochemical findings supported the diagnosis of combined high grade neuroendocrine carcinoma and hepatocellular carcinoma. DISCUSSION Cases of primary neuroendocrine tumors in the liver combined 82 with hepatocellular carcinoma are scarce. The uniqueness of this case lies in the fact that the neuroendocrine carcinoma component comprised more than 99% of the tumor area, and the minor hepatocellular carcinoma component was detected only by the immunohistochemical staining for HepPar-1. CONCLUSION To the best of our knowledge, this is the first case of combined neuroendocrine carcinoma and hepatocellular carcinoma in Egypt.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity.

Diagnostic role of glypican 3 and CD34 for differentiating hepatocellular carcinoma from nonmalignant hepatocellular lesions

Well-differentiated hepatocellular carcinoma (HCC) may be difficult to distinguish from a benign lesion. Glypican 3 (GPC-3) is an oncofetal protein, which has been demonstrated to be up-regulated in HCC. The aim of this study is to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the distinction between HCC and benign hepatic mimickers. This study was performed on 100 cases of formalin-fixed, paraffin-embedded cases of hepatic focal lesions obtained from the files of pathology laboratory of our university from 2009 to 2012. The following groups were studied: group A (n = 60) (hepatocellular malignant lesions) and group B (n = 40) (Hepatocellular nonmalignant lesions). All cases were stained with GPC-3 and CD34. Sensitivity, specificity, and positive and negative predictive values were calculated for both antibodies. Glypican 3 and complete CD34 staining pattern expression in group A was significantly higher than in group B. The results of costaining showed that, in HCCs, almost all the GPC-3-positive cases had a complete CD34 staining pattern, whereas in the 40 hepatocellular nonmalignant lesions, none stained up with the 2 markers. Therefore, although the sensitivity declined (82%), the specificity and positive predictive value (PPV) of costaining reached 100% and were greater than that observed for single staining with GPC-3 (specificity, 92.5%; PPV, 94.3%) or CD34 (specificity, 97.5%; PPV, 98.3%). Our data demonstrate that GPC-3 and CD34 costaining has better diagnostic value for differentiating HCC from nonmalignant hepatocellular lesions than does single staining.

Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.