Hebat Allah A Amin | Helwan University (original) (raw)

Papers by Hebat Allah A Amin

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence... more Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/β-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/β-catenin signaling proteins and microRNAs expression in HCC patients. Patients and methods: Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a- miR-106b- miR-99a- miR-148a- miR-125b- miR-30e- miR-183- miR-155- miR-199a- miR-199a3p- miR-24- miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/β-catenin pathway (β-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed. Results: Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p<0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/β-catenin pathway including β-catenin, APC and c-myc (p<0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection. Conclusion: Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/β-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.

Stem cell therapy represents a promising therapeutic avenue for cardiac disorders, including hea... more Stem cell therapy represents a promising therapeutic avenue for cardiac disorders, including heart failure.
Although stem cell transplantation showed encouraging preliminary results, the outcomes of clinical studies are
still unsatisfactory. This study aimed to compare the outcomes of two therapeutic approaches, in vivo co-delivery
of sodium hydrogen sulfide (NaHS) concomitant with bone marrow-derived mesenchymal stem cell (BMSC)
transplantation and in vitro preconditioning of BMSCs with NaHS, both of which are intended to promote the
success of stem cell therapy in rats with isoprenaline-induced heart failure. Heart failure developed 4 weeks after
the subcutaneous injection of isoprenaline (170 mg/kg) for 4 consecutive days. The in vivo approach involved the
co-delivery of intraperitoneally administered NaHS concomitant with BMSC transplantation for a period of 14
days. The in vitro approach involved preconditioning BMSCs with NaHS for 30 min before transplantation.
Compared to treatment with BMSCs alone, in vitro preconditioning of BMSCs with NaHS improved left ven-
tricular function as measured by echocardiography and electrocardiography and enhanced stem cell homing,
proliferation and differentiation as manifested by higher cardiac expression of GATA-4 and myocyte enhancer
factor 2. Moreover, the measurement of cardiac transforming growth factor beta 1 levels and histopathological
investigation revealed mitigated fibrosis and myocardial injury scores. Compared with BMSC therapy alone, the
in vivo approach enhanced stem cell homing and differentiation, alleviated fibrosis and augmented vascular
endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expression. In conclusion, NaHS
can potentiate the efficiency of BMSC therapy for heart failure by in vitro preconditioning or in vivo co-delivery.
The in vitro approach is superior with regard to improving cardiac function in addition to enhancing stem cell
proliferation, while the in vivo approach is superior with regard to increasing cardiac VEGF and eNOS expression.

Androgen receptor expression in hormone-negative breast cancers and its prognostic significance, 2018

Background/aim Breast carcinoma is a common, yet heterogeneous aggressive disease affecting relat... more Background/aim
Breast carcinoma is a common, yet heterogeneous aggressive disease affecting
relatively young patients. The androgen receptor (AR) is expressed in majority of
breast cancers and across the main breast cancer subtypes. The aim of this study
was to evaluate AR expression in hormone-negative breast cancer subtypes.
Materials and methods
Sixty cases of breast cancer were involved in this study; the samples were received in
the Department of Pathology of Kasr El-Aini Hospital, Cairo University, Egypt. The
expression of AR and human epidermal growth factor receptor-2 receptors were
studied by immunohistochemistry in 60 formalin-fixed paraffin-embedded selected
hormone-negative breast cancer surgical specimens. The immunohistochemistry
expression of the marker was correlated with the clinicopathological variables.
Results
Of the hormone-negative cases, 61.6% show positive AR expression, 89% of which
are invasive duct carcinoma, 68.3% are associated with ductal carcinoma in situ,
and 55% are human epidermal growth factor receptor-2-enriched subtype. A
significant correlation was found between the AR expression and tumor type.
There is no evident significant correlation with tumor grade, multicentricity or
lymphovascular invasion.
Conclusion
The AR has recently emerged as a useful marker for the further refinement of breast
cancer subtype classification. Antiandrogens are thought to markedly enhance
treatmentsandtobethefirsttargetedtherapyinhormone-negativebreast cancer cases

Abstract Lymphoepithelioma-like carcinoma (LELC) of the breast is an exceedingly rare varia... more Abstract Lymphoepithelioma-like carcinoma (LELC) of the breast is an exceedingly rare variant of mammary cancer. To our knowledge, only twenty - one cases have been reported in the literature. Diagnosis of this type of mammary carcinoma may be challenging, owing to its rarity and the histopathological similarity to common inflammatory and malignant lesions of the breast mainly granulomatous mastitis, medullary carcinoma, pleomorphic lobular carcinoma, lymphoma and other hematological malignancies. Our case is the 22nd case of lymphoepithelioma-like carcinoma reported in the breast, presenting with a palpable tender mass in a post-menopausal female. Her clinical picture had been mistaken for inflammatory disease. We present our case, with its detailed clinical history, radiological findings, histopathological and immune-histochemical findings along with a review of the literature. Highlighting this type of tumors may help in appropriate diagnosis. Moreover, studying the behavior of these rare neoplasms is essential to expedite treatment for this tumor type.

Egyptian Journal of Forensic Sciences, 2011

Background: Immunohistochemical techniques have proven to be effective for use in forensic pathol... more Background: Immunohistochemical techniques have proven to be effective for use in forensic pathology, as they can be applied to tissue samples fixed in formalin and embedded in paraffin. Histologic sections, including ischaemic and non-ischaemic myocardia, were studied via immunohistochemistry with three different antibodies to human cardiac troponin (cTnT), myoglobin (MB), and caspase 3, using a standard avidin-biotin-peroxidase system. Results: All antibodies detected cTnT or MB in the normal myocardium as well as its loss from the necrotic myocardium, in some cases before histologic evidence of necrosis was present. Loss was non-uniform and greater at the periphery of the infarcts than at their central regions. Usually, loss of cTnT appeared to be better than loss of MB; however, MB was more sensitive, and caspase 3 was the most sensitive. Caspase 3 was detected in areas with established ischaemia and in cases with coronary occlusion where there was no histologic evidence of necrosis, as well as in cases with latent infarction.

Molecular Neurobiology, 2015

3-Nitropropionic acid (3-NP)-induced neurotoxicity is an experimental model which mimics the path... more 3-Nitropropionic acid (3-NP)-induced neurotoxicity is an experimental model which mimics the pathology and motor abnormalities seen in Huntington&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (HD) in human. The present investigation was directed to estimate the role of rho kinase (ROCK) inhibition in the possible protective effect of fasudil and simvastatin in 3-NP-induced striatal neurodegeneration in rats. Animals were injected s.c. with 3-NP (20 mg/kg/day) for 1 week with or without administration of fasudil (10 mg/kg/day, p.o.) or simvastatin (20 mg/kg/day, p.o.). At the end of experiment, motor and behavioral abnormalities were evaluated. Animals were then sacrificed for measurement of mitochondrial membrane potential as well as succinate dehydrogenase (SDH) and caspase-3 activities in striatum. Moreover, tumor necrosis factor-alpha (TNF-α) level and protein expressions of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), ROCK, phosphorylated-Akt (p-Akt), endothelial and inducible nitric oxide synthase (eNOS and iNOS), Bax, and Bcl-2 were estimated. Finally, histological changes as demonstrated by striatum injury score, glial activation, and percentage of altered mitochondria were assessed. Both fasudil and simvastatin effectively inhibited 3-NP-induced behavioral, biochemical, and histological changes through inhibition of ROCK activity. However, fasudil provided more amelioration in histological changes, mitochondrial membrane potential and SDH activity in addition to p-Akt and PGC-1α protein expressions. The present study highlights a significant role of ROCK/p-Akt/eNOS pathway in the protective effects of fasudil and simvastatin on neurotoxicity and mitochondrial dysfunction induced by 3-NP in rats. Thus, specific inhibition of ROCK may be considered a promising new approach in the management of HD.

The relative contributions of trauma and disease may become a challenging acute medico-legal prob... more The relative contributions of trauma and disease may become a challenging acute medico-legal problem. Discussed here a case of sudden death due to myocardial infarction, associated with an external chest injury. Routine histopathological as well as immunohistochemical examination of the tissue samples using cTnT, MB, desmin and caspase-3 was made to evaluate and detect the extent of the myonecrosis. The presented case highlights the importance of detailed history by the medical examiner in cases of sudden death with associated injuries.

Background: Many immunohistochemical markers have been used in the postmortem detection of early ... more Background: Many immunohistochemical markers have been used in the postmortem detection of early myocardial infarction. In the present study we examined the role of Heart-type fatty acid binding protein (H-FABP), in the detection
of early myocardial infarction. We obtained samples from 40 human autopsy hearts
with/ without histopathological signs of ischemia.

Results: All cases of definite and probable myocardial infarction showed a well defined area of H-FABP depletion. All of the control cases showed strong H-FABP expression, except two markedly autolysed myocardial samples that showed affected
antigenicity.
Thus, we suggest H-FABP as being one of the valuable tools facing the problem of post mortem detection of early myocardial infarction/ischemi, but not in autolysis

Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive cl... more Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive clinical behavior that have no targeted therapy at present. Comparative studies for subtypes of triple negative group of invasive breast carcinoma are needed to detect any specific morphologic features of this group.
Results: The study included 40 cases of triple negative breast cancer. All cases were subjected to pathological study regarding gross and microscopic features. Results showed that 25 cases (62.5%) were invasive ductal carcinoma (NOS), 10 cases (25%) were medullary and 5 cases (12.5%) were metaplastic. The majority of cases were found to be T2 (17 cases representing 42.5%). 11 cases (27.5%) showed negative axillary node deposits, 11 cases (27.5%), showed deposits in 1-3 lymph nodes; 14 cases (35.0%) showed 4-9 nodal deposits and only 4 cases (10.0%) showed more than 9 nodes (10 %).
According to "Modified Bloom Richardson grading system", 24 cases (60%) were GIII.

Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive cl... more Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive clinical behavior that have no targeted therapy at present. Epidermal growth factor receptor (EGFR) expression has recently come into focus as an index for molecular targeting therapy. Histologic sections that included variable subtypes and grades of TNBCs were studied by immunohistochemistry with EGFR, using a standard avidin–biotin–peroxidase system.
Results: 22 cases showed variable positive reactivity for EGFR (55% of total cases).
Conclusions: the level of EGFR expression was relatively high as most studies stated, and agreed with most studies about the statement that EGFR expression is associated with worse prognosis.

Immunohistochemical techniques have proven to be effective for use in forensic pathology, as they... more Immunohistochemical techniques have proven to be effective for use in
forensic pathology, as they can be applied to tissue samples fixed in formalin and embedded in paraffin.
Histologic sections, including ischaemic and non-ischaemic myocardia, were studied via
immunohistochemistry with three different antibodies to human cardiac troponin (cTnT), myoglobin
(MB), and caspase 3, using a standard avidin–biotin–peroxidase system.
Results: All antibodies detected cTnT or MB in the normal myocardium as well as its loss from the
necrotic myocardium, in some cases before histologic evidence of necrosis was present. Loss was
non-uniform and greater at the periphery of the infarcts than at their central regions. Usually, loss
of cTnT appeared to be better than loss of MB; however, MB was more sensitive, and caspase 3 was
the most sensitive. Caspase 3 was detected in areas with established ischaemia and in cases with coronary
occlusion where there was no histologic evidence of necrosis, as well as in cases with latent
infarction.

Case Report Indian Journal of Forensic and Community Medicine, 2015;2(4):247-250 247 Acute myocar... more Case Report
Indian Journal of Forensic and Community Medicine, 2015;2(4):247-250 247
Acute myocardial infarction with concomitant
cardiac contusion: A case report

Hebat Allah A. Amin.1,*, Heba A. Abdelal.2, Dalia M. Aboulfadl.3
1,2Forensic Pathologist, Pathology Department, Egyptian Forensic Medicine Authority (EFMA),
St. Berum El- Tonsi, Zeinhum, Cairo, Egypt.
3Researcher, Pathology Department, Medical Division, National Research Centre, Cairo, Egypt.
*Corresponding Author:
E-mail: heba_forensicpathology_2912@hotmail.com; hebatallahahmedamin@gmail.com
ABSTRACT:
The relative contributions of trauma and disease may become a challenging acute medico-legal problem. Discussed here
a case of sudden death due to myocardial infarction, associated with an external chest injury. Routine histopathological as well as
immunohistochemical examination of the tissue samples using cTnT, MB, desmin and caspase-3 was made to evaluate and detect
the extent of the myonecrosis.
The presented case highlights the importance of detailed history by the medical examiner in cases of sudden death with associated
injuries.

3-Nitropropionic acid (3-NP)-induced neurotoxicity is an experimental model which mimics the path... more 3-Nitropropionic acid (3-NP)-induced neurotoxicity
is an experimental model which mimics the pathology
and motor abnormalities seen in Huntington’s disease (HD)
in human. The present investigation was directed to estimate
the role of rho kinase (ROCK) inhibition in the possible
protective effect of fasudil and simvastatin in 3-NPinduced
striatal neurodegeneration in rats. Animals were
injected s.c. with 3-NP (20 mg/kg/day) for 1 week with or
without administration of fasudil (10 mg/kg/day, p.o.) or
simvastatin (20 mg/kg/day, p.o.). At the end of experiment,
motor and behavioral abnormalities were evaluated. Animals
were then sacrificed for measurement of mitochondrial
membrane potential as well as succinate dehydrogenase
(SDH) and caspase-3 activities in striatum. Moreover, tumor
necrosis factor-alpha (TNF-α) level and protein expressions
of proliferator-activated receptor gamma coactivator 1-alpha
(PGC-1α), ROCK, phosphorylated-Akt (p-Akt), endothelial
and inducible nitric oxide synthase (eNOS and iNOS), Bax,
and Bcl-2 were estimated. Finally, histological changes as
demonstrated by striatum injury score, glial activation, and
percentage of altered mitochondria were assessed. Both
fasudil and simvastatin effectively inhibited 3-NP-induced
behavioral, biochemical, and histological changes through
inhibition of ROCK activity. However, fasudil provided
more amelioration in histological changes, mitochondrial
membrane potential and SDH activity in addition to p-Akt
and PGC-1α protein expressions. The present study highlights
a significant role of ROCK/p-Akt/eNOS pathway in
the protective effects of fasudil and simvastatin neurotoxicity
and mitochondrial dysfunction induced by 3-NP in rats.
Thus, specific inhibition of ROCK may be considered a
promising new approach in the management of HD.

Immunohistochemical techniques have proven effective inforensic pathology use as they can be appl... more Immunohistochemical techniques have proven effective inforensic pathology use as they can be applied to tissue samples fixed in formalin and embedded in paraffin. In thiswork, we selected a panel of antibodies, desmin, troponin T(cTnT), and myoglobin (MB), for the detection of earlymyocardial infarction in human autopsy hearts withsuspected sudden cardiac death to compare the sensitivityand the reliability of these markers and to study thepotential effect of autolysis on their sensitivity. Histologicsections from the myocardium from 20 autopsy cases werestudied by immunohistochemistry with the three differentantibodies, using a standard avidin–biotin–peroxidasesystem. Desmin, cTnT, and MB depletion occurred veryearly after ischemic injury and preceded the histologicevidence of necrosis.

International Journal of Toxicology, 2012

The current study aimed at investigating the potential hepatoprotective property and mechanism of... more The current study aimed at investigating the potential hepatoprotective property and mechanism of meloxicam (MEL) against carbon tetrachloride (CCl(4))-induced hepatocellular damage in rats. Subcutaneous administration of CCl(4) (2 mL/kg, twice/week for 8 weeks) induced hepatocellular damage substantiated by hematoxylin and eosin staining and significant elevation in serum aspartate transaminase, alanine transaminase, and total bilirubin. In addition, CCL(4) treatment led to elevation in liver contents of lipid peroxidation marker (malondialdehyde), prostaglandin E2, active caspase 3, and Terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and reduction in the activities of superoxide dismutase, catalase, glutathione-S-transferase, and reduced glutathione in the liver tissue. Prior oral treatment with MEL (5 mg/kg, twice/week) retained the normal liver histology and significantly restored all of these parameters close to normal values. These results demonstrated the hepatoprotective utility of MEL against the CCl(4)-induced liver injury which might ascribe to its antioxidant, free radical scavenging, antiapoptotic and anti-inflammatory effects.

Egyptian Journal of Forensic Sciences, 2011

Background Immunohistochemical techniques have proven to be effective for use in forensic patholo... more Background Immunohistochemical techniques have proven to be effective for use in forensic pathology, as they can be applied to tissue samples fixed in formalin and embedded in paraffin. Histologic sections, including ischaemic and non-ischaemic myocardia, were ...

Essay by Hebat Allah A Amin

This essay is aimed at our pathologists and medical examiners in the hope of convincing them that... more This essay is aimed at our pathologists and medical examiners in the hope of convincing them that it is not difficult or time-consuming to remove and fix the brain and spinal cord properly post mortem. We will try to give a quick review for the proper performance of brain autopsy, proper fixation, concise reminders of the forensic anatomy of the brain, followed by proper sampling of the brain, and the gross and microscopic findings to have the ability to interpret the autopsy findings competently, to appreciate the limitations of such interpretations, and to formulate comprehensible and meaningful reports.

Conference Presentations by Hebat Allah A Amin

Background: Human breast cancers are heterogeneous. This heterogeneity may originate due to diff... more Background: Human breast cancers are heterogeneous. This heterogeneity may
originate due to differences in the target cell population and/or it may be the result of
different combinations of mutations in a normal breast progenitor cell. New therapeutic
targets are needed in breast cancer, particularly in patients with TNBC and the related
basal-like subgroup. The Met tyrosine kinase receptor activates cell proliferation and a
strong relationship between high HGF/Met signaling and tumor progression was found.
The biologic roles of Androgen receptors in the breast are incompletely understood
since it is unclear whether the effects of androgens on breast cells are predominantly
proliferative or anti-proliferative. The purpose of this study is to determine the prognostic
value of Met and AR expression in ER negative breast cancer patients that might be
useful information to treat breast cancer especially TNBC.

Androgen receptor expression in hormone-negative breast cancers and its prognostic significance, 2018

Egyptian Journal of Forensic Sciences, 2011

Molecular Neurobiology, 2015

Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive cl... more Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive clinical behavior that have no targeted therapy at present. Epidermal growth factor receptor (EGFR) expression has recently come into focus as an index for molecular targeting therapy. Histologic sections that included variable subtypes and grades of TNBCs were studied by immunohistochemistry with EGFR, using a standard avidin–biotin–peroxidase system.
Results: 22 cases showed variable positive reactivity for EGFR (55% of total cases).
Conclusions: the level of EGFR expression was relatively high as most studies stated, and agreed with most studies about the statement that EGFR expression is associated with worse prognosis.

3-Nitropropionic acid (3-NP)-induced neurotoxicity is an experimental model which mimics the path... more 3-Nitropropionic acid (3-NP)-induced neurotoxicity
is an experimental model which mimics the pathology
and motor abnormalities seen in Huntington’s disease (HD)
in human. The present investigation was directed to estimate
the role of rho kinase (ROCK) inhibition in the possible
protective effect of fasudil and simvastatin in 3-NPinduced
striatal neurodegeneration in rats. Animals were
injected s.c. with 3-NP (20 mg/kg/day) for 1 week with or
without administration of fasudil (10 mg/kg/day, p.o.) or
simvastatin (20 mg/kg/day, p.o.). At the end of experiment,
motor and behavioral abnormalities were evaluated. Animals
were then sacrificed for measurement of mitochondrial
membrane potential as well as succinate dehydrogenase
(SDH) and caspase-3 activities in striatum. Moreover, tumor
necrosis factor-alpha (TNF-α) level and protein expressions
of proliferator-activated receptor gamma coactivator 1-alpha
(PGC-1α), ROCK, phosphorylated-Akt (p-Akt), endothelial
and inducible nitric oxide synthase (eNOS and iNOS), Bax,
and Bcl-2 were estimated. Finally, histological changes as
demonstrated by striatum injury score, glial activation, and
percentage of altered mitochondria were assessed. Both
fasudil and simvastatin effectively inhibited 3-NP-induced
behavioral, biochemical, and histological changes through
inhibition of ROCK activity. However, fasudil provided
more amelioration in histological changes, mitochondrial
membrane potential and SDH activity in addition to p-Akt
and PGC-1α protein expressions. The present study highlights
a significant role of ROCK/p-Akt/eNOS pathway in
the protective effects of fasudil and simvastatin neurotoxicity
and mitochondrial dysfunction induced by 3-NP in rats.
Thus, specific inhibition of ROCK may be considered a
promising new approach in the management of HD.

International Journal of Toxicology, 2012

Egyptian Journal of Forensic Sciences, 2011