Effect of neoadjuvant chemoradiotherapy on p53 and SOX2 protein expression in esophageal adenocarcinoma

2020 ◽  
Vol 14 (9) ◽  
pp. 785-793
Author(s):  
Lucia Suzuki ◽  
Daan Nieboer ◽  
Jan JB van Lanschot ◽  
Manon CW Spaander ◽  
Leendert HJ Looijenga ◽  
...  
Keyword(s):  
Protein Expression ◽  
Esophageal Adenocarcinoma ◽  
Staining Pattern ◽  
Neoadjuvant Chemoradiotherapy ◽  
Wild Type ◽  
Aberrant Expression ◽  
Methods Comparison ◽  
Sox2 Expression ◽  
Before And After

Aim: To determine if neoadjuvant chemoradiotherapy (nCRT) affects p53 and SOX2 expression in esophageal adenocarcinoma (EAC). Materials & methods: Comparison of p53 and SOX2 expression in 100 paired pre- and post-nCRT EAC samples. Results: Aberrant p53 was largely concordant (75/83, 90%), while 13/18 (72%) pre-nCRT samples with wild-type (WT) p53 staining, showed aberrant staining in paired post-nCRT samples. Similarly, 31/45 (69%) with previous WT SOX2 showed SOX2 loss in paired post-nCRT samples, whereas aberrant SOX2 loss was concordant in 50/55 (91%) cases. The prognostic values of both markers regarding survival differ before and after nCRT. Conclusion: Aberrant expression of p53 and SOX2 staining in EAC tissue is unaffected by nCRT. Conversely, the WT-staining pattern frequently changed to aberrant expression.

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy

2017 ◽  
Vol 265 (2) ◽  
pp. 347-355 ◽  
Author(s):  
Sophie H. van Olphen ◽  
Katharina Biermann ◽  
Joel Shapiro ◽  
Bas P. L. Wijnhoven ◽  
Eelke L. A. Toxopeus ◽  
...  
Keyword(s):  
Protein Expression ◽  
Esophageal Adenocarcinoma ◽  
Neoadjuvant Chemoradiotherapy

scholarly journals Assessment of the Molecular Heterogeneity of E-Cadherin Expression in Invasive Lobular Breast Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 295
Author(s):  
John Alexander ◽  
Odette Mariani ◽  
Celine Meaudre ◽  
Laetitia Fuhrmann ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Molecular Heterogeneity ◽  
Breast Cancers ◽  
Wild Type ◽  
Driver Genes ◽  
Methylation Array ◽  
Aberrant Expression ◽  
Heterogeneous Expression ◽  
Invasive Lobular Breast Cancer ◽  
E Cadherin

Mutations and loss of E-cadherin protein expression define the vast majority of invasive lobular carcinomas. In a subset of these cases, the heterogeneous expression of E-cadherin is observed either as wild-type (strong membranous) expression or aberrant expression (cytoplasmic expression). However, it is unclear as to whether the two components would be driven by distinct genetic or epigenetic alterations. Here, we used whole genome DNA sequencing and methylation array profiling of two separately dissected components of nine invasive lobular carcinomas with heterogeneous E-cadherin expression. E-cadherin negative and aberrant/positive components of E-cadherin heterogeneous tumours showed a similar mutational, copy number and promoter methylation repertoire, suggesting they arise from a common ancestor, as opposed to the collision of two independent tumours. We found that the majority of E-cadherin heterogeneous tumours harboured CDH1 mutations in both the E-cadherin negative and aberrant/positive components together with somatic mutations in additional driver genes known to be enriched in both pure invasive carcinomas of no special type and invasive lobular breast cancers, whereas these were less commonly observed in CDH1 wild-type tumours. CDH1 mutant tumours also exhibited a higher mutation burden as well as increased presence of APOBEC-dependent mutational signatures 2 and 13 compared to CDH1 wild-type tumours. Together, our results suggest that regardless of E-cadherin protein expression, tumours showing heterogeneous expression of E-cadherin should be considered as part of the spectrum of invasive lobular breast cancers.

Ultrastructure of Melanin Formation in Curvularia sp., Alternaria sp., and Drechslera Sorokiniana

1977 ◽  
Vol 35 ◽  
pp. 398-399
Author(s):  
M. H. Wheeler ◽  
W. J. Tolmsoff ◽  
A. A. Bell
Keyword(s):  
Potassium Phosphate ◽  
Thielaviopsis Basicola ◽  
Wild Type ◽  
Potassium Phosphate Buffer ◽  
Transmission Microscopy ◽  
Electron Transmission ◽  
Melanin Formation ◽  
Before And After ◽  
Alternaria Sp ◽  
Electron Transmission Microscopy

(+)-Scytalone [3,4-dihydro-3,6,8-trihydroxy-l-(2Hj-naphthalenone] and 1,8-di- hydroxynaphthalene (DHN) have been proposed as intermediates of melanin synthesis in the fungi Verticillium dahliae (1, 2, 3, 4) and Thielaviopsis basicola (4, 5). Scytalone is enzymatically dehydrated by V. dahliae to 1,3,8-trihydroxynaphthalene which is then reduced to (-)-vermelone [(-)-3,4- dihydro-3,8-dihydroxy-1(2H)-naphthalenone]. Vermelone is subsequently dehydrated to DHN which is enzymatically polymerized to melanin.Melanin formation in Curvularia sp., Alternaria sp., and Drechslera soro- kiniana was examined by light and electron-transmission microscopy. Wild-type isolates of each fungus were compared with albino mutants before and after treatment with 1 mM scytalone or 0.1 mM DHN in 50 mM potassium phosphate buffer, pH 7.0. Both chemicals were converted to dark pigments in the walls of hyphae and conidia of the albino mutants. The darkened cells were similar in appearance to corresponding cells of the wild types under the light microscope.

scholarly journals A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yağmur Demircan Yalçın ◽  
Taylan Berkin Töral ◽  
Sertan Sukas ◽  
Ender Yıldırım ◽  
Özge Zorlu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Drug Resistant ◽  
Wild Type ◽  
Gene Expressions ◽  
Before And After ◽  
The Difference ◽  
Selection Of ◽  
Resistant Cells

AbstractWe report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance.

scholarly journals Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons

2020 ◽  
Vol 22 (1) ◽  
pp. 145
Author(s):  
Rohan Umesh Parekh ◽  
Srinivas Sriramula
Keyword(s):  
Protein Expression ◽  
Renin Angiotensin System ◽  
Neuronal Cultures ◽  
Wild Type ◽  
High Concentration ◽  
Neurogenic Hypertension ◽  
B1 Receptor ◽  
Gene And Protein Expression ◽  
Kinin B1 Receptor ◽  
Specific Antagonist

Angiotensin converting enzyme 2 (ACE2) is a critical component of the compensatory axis of the renin angiotensin system. Alterations in ACE2 gene and protein expression, and activity mediated by A Disintegrin And Metalloprotease 17 (ADAM17), a member of the “A Disintegrin And Metalloprotease” (ADAM) family are implicated in several cardiovascular and neurodegenerative diseases. We previously reported that activation of kinin B1 receptor (B1R) in the brain increases neuroinflammation, oxidative stress and sympathoexcitation, leading to the development of neurogenic hypertension. We also showed evidence for ADAM17-mediated ACE2 shedding in neurons. However, whether kinin B1 receptor (B1R) activation has any role in altering ADAM17 activity and its effect on ACE2 shedding in neurons is not known. In this study, we tested the hypothesis that activation of B1R upregulates ADAM17 and results in ACE2 shedding in neurons. To test this hypothesis, we stimulated wild-type and B1R gene-deleted mouse neonatal primary hypothalamic neuronal cultures with a B1R-specific agonist and measured the activities of ADAM17 and ACE2 in neurons. B1R stimulation significantly increased ADAM17 activity and decreased ACE2 activity in wild-type neurons, while pretreatment with a B1R-specific antagonist, R715, reversed these changes. Stimulation with specific B1R agonist Lys-Des-Arg9-Bradykinin (LDABK) did not show any effect on ADAM17 or ACE2 activities in neurons with B1R gene deletion. These data suggest that B1R activation results in ADAM17-mediated ACE2 shedding in primary hypothalamic neurons. In addition, stimulation with high concentration of glutamate significantly increased B1R gene and protein expression, along with increased ADAM17 and decreased ACE2 activities in wild-type neurons. Pretreatment with B1R-specific antagonist R715 reversed these glutamate-induced effects suggesting that indeed B1R is involved in glutamate-mediated upregulation of ADAM17 activity and ACE2 shedding.

scholarly journals Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Receptor Expression ◽  
Wild Type ◽  
High Fat ◽  
Renal Gluconeogenesis ◽  
Mrna And Protein Expression ◽  
Polymerase Chain ◽  
Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

scholarly journals Expression of SOX2 and OCT4 in odontogenic cysts and tumors

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ekarat Phattarataratip ◽  
Tarit Panitkul ◽  
Watunyoo Khodkaew ◽  
Pattarapong Anupuntanun ◽  
Jirapat Jaroonvechatam ◽  
...  
Keyword(s):  
Cell Types ◽  
Odontogenic Cysts ◽  
Positive Staining ◽  
Stem Cell Markers ◽  
Aberrant Expression ◽  
Future Studies ◽  
Sox2 Expression ◽  
Cells Of Origin ◽  
Dentigerous Cysts ◽  
Patient Prognosis

Abstract Background Aberrant expression of stem cell markers has been observed in several types of neoplasms. This trait attributes to the acquired stem-like property of tumor cells and can impact patient prognosis. The objective of this study was to comparatively analyze the expression and significance of SOX2 and OCT4 in various types of odontogenic cysts and tumors. Methods Fifty-five cases of odontogenic cysts and tumors, including 15 ameloblastomas (AM), 5 adenomatoid odontogenic tumors (AOT), 5 ameloblastic fibromas (AF), 5 calcifying odontogenic cysts (COC), 10 dentigerous cysts (DC) and 15 odontogenic keratocysts (OKC) were investigated for the expression of SOX2 and OCT4 immunohistochemically. Results Most OKCs (86.7 %) and all AFs expressed SOX2 in more than 50 % of epithelial cells. Its immunoreactivity was moderate-to-strong in all epithelial cell types in both lesions. In contrast, SOX2 expression was undetectable in AOTs and limited to the ameloblast-like cells in a minority of AM and COC cases. Most DCs showed positive staining in less than 25 % of cystic epithelium. Significantly greater SOX2 expression was noted in OKC compared with DC or AM, and in AF compared with COC or AOT. OCT4 rarely expressed in odontogenic lesions with the immunoreactivity being mild and present exclusively in OKCs. Conclusions SOX2 is differentially expressed in odontogenic cysts and tumors. This could be related to their diverse cells of origin or stages of histogenesis. The overexpression of SOX2 and OCT4 in OKC indicates the acquired stem-like property. Future studies should investigate whether the overexpression of OCT4 and SOX2 contributes to the aggressive behaviors of the tumors.

scholarly journals The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1791
Author(s):  
Zhe Su ◽  
Yang Yang ◽  
Shengru Wang ◽  
Sen Zhao ◽  
Hengqiang Zhao ◽  
...  
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Protein Expression ◽  
Rare Variants ◽  
Congenital Scoliosis ◽  
Loss Of Function ◽  
Wild Type ◽  
Cellular Location ◽  
Mutational Landscape

Depletion of ptk7 is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of PTK7 has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of PTK7 in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study. We identified a total of four rare variants in CS and four variants in AIS, including one protein truncating variant (c.464_465delAC) in a patient with CS. We then explored the effects of these variants on protein expression and sub-cellular location. We confirmed that the c.464_465delAC variant causes loss-of-function (LoF) of PTK7. In addition, the c.353C>T and c.2290G>A variants identified in two patients with AIS led to reduced protein expression of PTK7 as compared to that of the wild type. In conclusion, LoF and hypomorphic variants are associated with CS and AIS, respectively.

scholarly journals Comparison of protein expression during wild-type, and E1B-55k-deletion, adenovirus infection using quantitative time-course proteomics

2017 ◽  
Vol 98 (6) ◽  
pp. 1377-1388 ◽  
Author(s):  
Yen Rong Fu ◽  
Andrew S. Turnell ◽  
Simon Davis ◽  
Kate J. Heesom ◽  
Vanessa C. Evans ◽  
...  
Keyword(s):  
Protein Expression ◽  
Time Course ◽  
Adenovirus Infection ◽  
Wild Type

scholarly journals Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

2021 ◽  
Author(s):  
Jorge C.G. Blanco ◽  
Lori McGinnes-Cullen ◽  
Arash Kamali ◽  
Fatoumata Sylla ◽  
Marina Boukhavalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Cotton Rat ◽  
Before And After ◽  
Boost Immunization ◽  
Cotton Rats ◽  
Antibody Titers ◽  
Syncytial Virus ◽  
Efficient Transfer

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life.  In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19).  Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization.  We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth.   However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age.  This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy.  The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

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