Supplementary Figure S4: Effect of sorafenib with or without iRGD on MAPK phosphorylation levels ... more Supplementary Figure S4: Effect of sorafenib with or without iRGD on MAPK phosphorylation levels in the HepG2 xenografts from the different treatment groups.
This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthra... more This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthranilic acid (HA). The complex [Y2(HA)6(H2O)4] Cl6.2C2H5OH (C1) was obtained as single crystals that its X-ray analysis revealed its triclinic P-1 space group in addition to anti-prismatic geometry around each of the yttrium ions. In the complex, the anthranilic acid ligands are bidentate, zwitter ionic and neutral, and the yttrium ions’ charge is only compensated by six chloride ions. The cytotoxicity of this complex against human breast cancer MDA-MB-231 cells, prostate cancer PC-3 cells, and bladder cancer T-24 cells was evaluated. This yttrium complex displayed more cytotoxic activity against the bladder cancer cells with an IC50 value of 307.7 μg/ml (223 μM). On the other hand, the activities of complex C1 against the MDA-MB-231 and PC-3 cells were less significant respectively with IC50 values of 1097 μg/ml (796 μM) and 921 μg/ml (669 μM).
Two antimony complexes {[Sb(L1)Cl2] C1 and [Sb(L2)Cl2] C2} with the thiosemicarbazone ligands {HL... more Two antimony complexes {[Sb(L1)Cl2] C1 and [Sb(L2)Cl2] C2} with the thiosemicarbazone ligands {HL1 = 4-(2,4-dimethylphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were introduced. The structures were elucidated on the basis of a CHNS analysis, spectroscopic techniques (UV-Vis and FT-IR), and DMF solution electrical conductivities. Single crystal X-ray diffraction analysis of complex C1 assigned the complex pseudo-octahedral geometry and triclinic P-1 space group. Only the ligand HL1 and its derived complex C1 displayed antifungal activities against Candida albicans and this activity was enhanced from 10 mm to 21 mm for the respective complex, which is the same activity given by the drug “Amphotericin B”. The ligands HL1 and HL2 gave inhibitions, respectively, of 14 and 10 mm against Staphylococcus aureus and 15 and 10 mm against Escherichia coli; however, complexes C1 and C2 increased these inhibit...
New complexes of trivalent cobalt with substituted thiosemicarbazone ligands having an NNS donor ... more New complexes of trivalent cobalt with substituted thiosemicarbazone ligands having an NNS donor system {HL1 = 4-(4-nitrophenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were synthesized via the in situ oxidation of divalent cobalt chloride accompanying its addition to the ligands. The complexes C1 and C2 were characterized via elemental (CHNS) analysis and 1H NMR, FT-IR and UV-Vis. spectroscopic data. Further, conductometric studies on the DMF solutions of the complexes indicated their 1:1 nature, and their diamagnetism revealed the low-spin trivalent oxidation state of the cobalt in the complexes. The X-ray diffraction analysis of complex C1 indicated that it crystallizes in the triclinic space group P-1. The metal exhibits an octahedral environment built by two anionic ligands bound via pyridine nitrogen, imine nitrogen and thiol sulfur atoms. The complex is counterbalanced by a chloride ion. In a...
MicroRNAs (miRNAs) are small RNA molecules with perfect or imperfect homology to their target mRN... more MicroRNAs (miRNAs) are small RNA molecules with perfect or imperfect homology to their target mRNA. They have been shown to specifically interfere with the expression of their target protein(s). Moreover, microRNAs play an important role in the pathogenesis of cancer, where some microRNAs act as tumor suppressors by targeting lethal oncogenes, and others act as oncogenes by targeting suppressor genes. Thus, microRNAs can be involved directly or indirectly in important cellular processes such as proliferation, differentiation and apoptosis. Understanding the functions and importance of microRNAs could lead to the discovery of new strategies for controlling of cancer. This thesis was aiming at the possibility of using non-viral delivery systems for microRNAs into mammalian cell lines, and examined their efficacies. To this end, three different transfection reagents, linear Jet-PEI, branched PEI F25-LMW and INTERFERin, were used in vitro, either commercially available or prepared in ou...
Jaundice (icterus) describes the yellow discoloration of the skin and mucous membranes, and other... more Jaundice (icterus) describes the yellow discoloration of the skin and mucous membranes, and other tissues by excess bilirubin, which is the degradation product of hemoglobin. The main objective is to hold comparison between MRCP and ERCP in patients with obstructive jaundice. Prospective and descriptive study deal with comparative study between Endoscopic Retrograde Cholangio pancreato graphy and Magnetic resonance cholangio pancreatography in diagnoses of obstructive jaundice among Sudanese population. In results The data was collected, classified, analyzed by using Statistical package for social science the analysis of the result found that the female patients were (56.7% ) VS (43.3%) males, most of the patients affected age group in the over 5 th decade (50%), most of the patients were employee (40%), most of the patients were married (93.3%), most of the patients were from center of Sudan (73.3%),and the patients with clinical diagnosis of obstructive jaundice were (76.7%). ERCP...
Background Retro-maxillary recess of the sphenoid sinus is an area that is yet to have appropriat... more Background Retro-maxillary recess of the sphenoid sinus is an area that is yet to have appropriate description in the literature and usually overlooked. The objective of the current study was to determine the incidence and detailed description of the retromaxillary recess of the sphenoid sinus by multi-slices computed tomography (MSCT) in adults. Paranasal MSCT scan of asymptomatic adults was done for all our subjects to obtain delicate anatomical details of the recess using coronal, axial, and sagittal reformatted capability. Each sphenoid sinus in the CT was revised to find and describe the retro-maxillary recess of the sphenoid sinus regarding its extensions and dimensions. Results This study included 100 adult subjects (200 sphenoid sinuses); retro-maxillary recess was detected in 16.5% (33 sides) of them using MSCT. They were distributed in 20 subjects (20% of all examined sphenoid sinuses). Sixty-five percent of reported recesses were bilateral. Range of antero-posterior diame...
Herein, a simple, economical and low temperature synthesis of leaf-shaped CuO nanosheets is repor... more Herein, a simple, economical and low temperature synthesis of leaf-shaped CuO nanosheets is reported. As-synthesized CuO was examined through different techniques including field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), X-ray diffraction (XRD), fourier transform infrared spectroscopic (FTIR) and Raman spectroscopy to ascertain the purity, crystal phase, morphology, vibrational, optical and diffraction features. FESEM and TEM images revealed a thin leaf-like morphology for CuO nanosheets. An interplanar distance of ~0.25 nm corresponding to the (110) diffraction plane of the monoclinic phase of the CuO was revealed from the HRTEM images XRD analysis indicated a monoclinic tenorite crystalline phase of the synthesized CuO nanosheets. The average crystallite size for leaf-shaped CuO nanosheets was found to be 14.28 nm. Furthermore, a chemo-resistive-type gas sensor based on ...
Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (... more Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (miR-30e) and microRNA-223 (miR-223) as diagnostic biomarkers for early diagnosis of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. Methods. The study included three groups, the first group included thirty patients with HCC associated with HCV, the second group included thirty patients with cirrhosis with HCV and the third group included thirty healthy control subjects. Blood samples were obtained for determination of serum expression of miR-30e and miR-223 by real time polymerase chain reaction. Results. There was significant decrease of miR-30e of expression in patients with HCC (0.16 ± 0.1) compared to both patients with cirrhosis (0.4 ± 0.2, P<0.01) and healthy control subjects (1.2 ± 0.4, P<0.001). There was also significant reduction of miR-223 expression levels in patients with HCC (0.2 ± 0.1) compared to patients with cirrhosis (0.5 ± 0.2, ...
International Journal of Pharmaceutical Sciences and Drug Research, 2019
Cancer is a leading cause of death throughout the world which suffers from treatment failures mai... more Cancer is a leading cause of death throughout the world which suffers from treatment failures mainly due to intensive toxicity and lack of effectiveness of conventional drugs. The application of nanotechnology in cancer treatment promises to overcome the drawbacks of conventional drugs/dosage forms and improve their therapeutic efficacy. Nanomaterials have novel properties that influence their in vivo performance. The biological behaviour of nanotechnology-based medicines in the body, which is different from the in vivo performance of conventional drug delivery systems, may provide benefits in pharmaceutical and/or clinical applications including, enhancements in solubility, stability, therapeutic efficacy, minimized side effects, and treatment of diseases. This paper discusses the unique characteristics and distinguished advantages of nanomaterials as anticancer drug carriers. Physicochemical properties of nanomaterials are critical parameters to their clinical translation. Hence, ...
Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone... more Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone‐replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine‐specific deletion of ERβ (ERβKOVil) were generated using the Cre‐LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high‐throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S‐Seq data, and the distribution of bacterial species was...
Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suf... more Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L - made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® - as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of dilu...
The discovery of oestrogen receptor β (ERβ/ESR2) was a landmark discovery. Its reported expressio... more The discovery of oestrogen receptor β (ERβ/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ERα (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ERβ antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ERβ in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ERβ protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies ...
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 6, 2017
A role of Dicer, which converts precursor miRNAs to mature miRNAs, in the tumor-promoting effect ... more A role of Dicer, which converts precursor miRNAs to mature miRNAs, in the tumor-promoting effect of hypoxia is currently emerging in some tumor entities. Its role in hepatocellular carcinoma (HCC) is unknown. HepG2 and Huh-7 cells were stably transfected with an inducible Dicer expression vector and were exposed to hypoxia/normoxia. HepG2-Dicer xenografts were established in nude mice; hypoxic areas and Dicer were detected in HCC xenografts and HCCs from mice with endogenous hepatocarcinogenesis; epithelial mesenchymal transition (EMT) markers were analyzed by immunohistochemistry or by immunoblotting. The correlation between Dicer and carbonic anhydrase 9 (CA9), a marker of hypoxia, was investigated in resected human HCCs. Hypoxia increased EMT markers in vitro and in vivo and led to a downregulation of Dicer in HCC cells. The levels of Dicer were down-regulated in hypoxic tumor regions in mice with endogenous hepatocarcinogenesis and in HepG2 xenografts. In human HCCs the levels o...
Supplementary Figure S4: Effect of sorafenib with or without iRGD on MAPK phosphorylation levels ... more Supplementary Figure S4: Effect of sorafenib with or without iRGD on MAPK phosphorylation levels in the HepG2 xenografts from the different treatment groups.
This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthra... more This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthranilic acid (HA). The complex [Y2(HA)6(H2O)4] Cl6.2C2H5OH (C1) was obtained as single crystals that its X-ray analysis revealed its triclinic P-1 space group in addition to anti-prismatic geometry around each of the yttrium ions. In the complex, the anthranilic acid ligands are bidentate, zwitter ionic and neutral, and the yttrium ions’ charge is only compensated by six chloride ions. The cytotoxicity of this complex against human breast cancer MDA-MB-231 cells, prostate cancer PC-3 cells, and bladder cancer T-24 cells was evaluated. This yttrium complex displayed more cytotoxic activity against the bladder cancer cells with an IC50 value of 307.7 μg/ml (223 μM). On the other hand, the activities of complex C1 against the MDA-MB-231 and PC-3 cells were less significant respectively with IC50 values of 1097 μg/ml (796 μM) and 921 μg/ml (669 μM).
Two antimony complexes {[Sb(L1)Cl2] C1 and [Sb(L2)Cl2] C2} with the thiosemicarbazone ligands {HL... more Two antimony complexes {[Sb(L1)Cl2] C1 and [Sb(L2)Cl2] C2} with the thiosemicarbazone ligands {HL1 = 4-(2,4-dimethylphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were introduced. The structures were elucidated on the basis of a CHNS analysis, spectroscopic techniques (UV-Vis and FT-IR), and DMF solution electrical conductivities. Single crystal X-ray diffraction analysis of complex C1 assigned the complex pseudo-octahedral geometry and triclinic P-1 space group. Only the ligand HL1 and its derived complex C1 displayed antifungal activities against Candida albicans and this activity was enhanced from 10 mm to 21 mm for the respective complex, which is the same activity given by the drug “Amphotericin B”. The ligands HL1 and HL2 gave inhibitions, respectively, of 14 and 10 mm against Staphylococcus aureus and 15 and 10 mm against Escherichia coli; however, complexes C1 and C2 increased these inhibit...
New complexes of trivalent cobalt with substituted thiosemicarbazone ligands having an NNS donor ... more New complexes of trivalent cobalt with substituted thiosemicarbazone ligands having an NNS donor system {HL1 = 4-(4-nitrophenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2,5-dimethoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} were synthesized via the in situ oxidation of divalent cobalt chloride accompanying its addition to the ligands. The complexes C1 and C2 were characterized via elemental (CHNS) analysis and 1H NMR, FT-IR and UV-Vis. spectroscopic data. Further, conductometric studies on the DMF solutions of the complexes indicated their 1:1 nature, and their diamagnetism revealed the low-spin trivalent oxidation state of the cobalt in the complexes. The X-ray diffraction analysis of complex C1 indicated that it crystallizes in the triclinic space group P-1. The metal exhibits an octahedral environment built by two anionic ligands bound via pyridine nitrogen, imine nitrogen and thiol sulfur atoms. The complex is counterbalanced by a chloride ion. In a...
MicroRNAs (miRNAs) are small RNA molecules with perfect or imperfect homology to their target mRN... more MicroRNAs (miRNAs) are small RNA molecules with perfect or imperfect homology to their target mRNA. They have been shown to specifically interfere with the expression of their target protein(s). Moreover, microRNAs play an important role in the pathogenesis of cancer, where some microRNAs act as tumor suppressors by targeting lethal oncogenes, and others act as oncogenes by targeting suppressor genes. Thus, microRNAs can be involved directly or indirectly in important cellular processes such as proliferation, differentiation and apoptosis. Understanding the functions and importance of microRNAs could lead to the discovery of new strategies for controlling of cancer. This thesis was aiming at the possibility of using non-viral delivery systems for microRNAs into mammalian cell lines, and examined their efficacies. To this end, three different transfection reagents, linear Jet-PEI, branched PEI F25-LMW and INTERFERin, were used in vitro, either commercially available or prepared in ou...
Jaundice (icterus) describes the yellow discoloration of the skin and mucous membranes, and other... more Jaundice (icterus) describes the yellow discoloration of the skin and mucous membranes, and other tissues by excess bilirubin, which is the degradation product of hemoglobin. The main objective is to hold comparison between MRCP and ERCP in patients with obstructive jaundice. Prospective and descriptive study deal with comparative study between Endoscopic Retrograde Cholangio pancreato graphy and Magnetic resonance cholangio pancreatography in diagnoses of obstructive jaundice among Sudanese population. In results The data was collected, classified, analyzed by using Statistical package for social science the analysis of the result found that the female patients were (56.7% ) VS (43.3%) males, most of the patients affected age group in the over 5 th decade (50%), most of the patients were employee (40%), most of the patients were married (93.3%), most of the patients were from center of Sudan (73.3%),and the patients with clinical diagnosis of obstructive jaundice were (76.7%). ERCP...
Background Retro-maxillary recess of the sphenoid sinus is an area that is yet to have appropriat... more Background Retro-maxillary recess of the sphenoid sinus is an area that is yet to have appropriate description in the literature and usually overlooked. The objective of the current study was to determine the incidence and detailed description of the retromaxillary recess of the sphenoid sinus by multi-slices computed tomography (MSCT) in adults. Paranasal MSCT scan of asymptomatic adults was done for all our subjects to obtain delicate anatomical details of the recess using coronal, axial, and sagittal reformatted capability. Each sphenoid sinus in the CT was revised to find and describe the retro-maxillary recess of the sphenoid sinus regarding its extensions and dimensions. Results This study included 100 adult subjects (200 sphenoid sinuses); retro-maxillary recess was detected in 16.5% (33 sides) of them using MSCT. They were distributed in 20 subjects (20% of all examined sphenoid sinuses). Sixty-five percent of reported recesses were bilateral. Range of antero-posterior diame...
Herein, a simple, economical and low temperature synthesis of leaf-shaped CuO nanosheets is repor... more Herein, a simple, economical and low temperature synthesis of leaf-shaped CuO nanosheets is reported. As-synthesized CuO was examined through different techniques including field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), X-ray diffraction (XRD), fourier transform infrared spectroscopic (FTIR) and Raman spectroscopy to ascertain the purity, crystal phase, morphology, vibrational, optical and diffraction features. FESEM and TEM images revealed a thin leaf-like morphology for CuO nanosheets. An interplanar distance of ~0.25 nm corresponding to the (110) diffraction plane of the monoclinic phase of the CuO was revealed from the HRTEM images XRD analysis indicated a monoclinic tenorite crystalline phase of the synthesized CuO nanosheets. The average crystallite size for leaf-shaped CuO nanosheets was found to be 14.28 nm. Furthermore, a chemo-resistive-type gas sensor based on ...
Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (... more Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (miR-30e) and microRNA-223 (miR-223) as diagnostic biomarkers for early diagnosis of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. Methods. The study included three groups, the first group included thirty patients with HCC associated with HCV, the second group included thirty patients with cirrhosis with HCV and the third group included thirty healthy control subjects. Blood samples were obtained for determination of serum expression of miR-30e and miR-223 by real time polymerase chain reaction. Results. There was significant decrease of miR-30e of expression in patients with HCC (0.16 ± 0.1) compared to both patients with cirrhosis (0.4 ± 0.2, P<0.01) and healthy control subjects (1.2 ± 0.4, P<0.001). There was also significant reduction of miR-223 expression levels in patients with HCC (0.2 ± 0.1) compared to patients with cirrhosis (0.5 ± 0.2, ...
International Journal of Pharmaceutical Sciences and Drug Research, 2019
Cancer is a leading cause of death throughout the world which suffers from treatment failures mai... more Cancer is a leading cause of death throughout the world which suffers from treatment failures mainly due to intensive toxicity and lack of effectiveness of conventional drugs. The application of nanotechnology in cancer treatment promises to overcome the drawbacks of conventional drugs/dosage forms and improve their therapeutic efficacy. Nanomaterials have novel properties that influence their in vivo performance. The biological behaviour of nanotechnology-based medicines in the body, which is different from the in vivo performance of conventional drug delivery systems, may provide benefits in pharmaceutical and/or clinical applications including, enhancements in solubility, stability, therapeutic efficacy, minimized side effects, and treatment of diseases. This paper discusses the unique characteristics and distinguished advantages of nanomaterials as anticancer drug carriers. Physicochemical properties of nanomaterials are critical parameters to their clinical translation. Hence, ...
Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone... more Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone‐replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine‐specific deletion of ERβ (ERβKOVil) were generated using the Cre‐LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high‐throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S‐Seq data, and the distribution of bacterial species was...
Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suf... more Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L - made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® - as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of dilu...
The discovery of oestrogen receptor β (ERβ/ESR2) was a landmark discovery. Its reported expressio... more The discovery of oestrogen receptor β (ERβ/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ERα (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ERβ antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ERβ in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ERβ protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies ...
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 6, 2017
A role of Dicer, which converts precursor miRNAs to mature miRNAs, in the tumor-promoting effect ... more A role of Dicer, which converts precursor miRNAs to mature miRNAs, in the tumor-promoting effect of hypoxia is currently emerging in some tumor entities. Its role in hepatocellular carcinoma (HCC) is unknown. HepG2 and Huh-7 cells were stably transfected with an inducible Dicer expression vector and were exposed to hypoxia/normoxia. HepG2-Dicer xenografts were established in nude mice; hypoxic areas and Dicer were detected in HCC xenografts and HCCs from mice with endogenous hepatocarcinogenesis; epithelial mesenchymal transition (EMT) markers were analyzed by immunohistochemistry or by immunoblotting. The correlation between Dicer and carbonic anhydrase 9 (CA9), a marker of hypoxia, was investigated in resected human HCCs. Hypoxia increased EMT markers in vitro and in vivo and led to a downregulation of Dicer in HCC cells. The levels of Dicer were down-regulated in hypoxic tumor regions in mice with endogenous hepatocarcinogenesis and in HepG2 xenografts. In human HCCs the levels o...
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