scholarly journals Low Expression of Occludin in the Melanoma Patient

2019 ◽  
Vol 14 (4) ◽  
pp. 272-278
Author(s):  
Pouri Salehi ◽  
Farzaneh Tafvizi ◽  
Kambiz Kamyab Hesari

Background & Objective: Malignant melanoma is the fatal cutaneous neoplasm which is curable by the early diagnosis. The expression of occludin protein which is an integral membrane protein is altered in an epithelial-to-mesenchymal transition. Although, recent studies provide sufficient evidence supporting the functional importance of occludin in cancer, the prognostic significance of occludin expression levels in melanoma remains obscure. The aim of this study was to determine occludin expression level and itscorrelation with clinicopathological features of the patients with melanoma. Methods: The occludin mRNA level was compared between paraffin-embedded tissues of 40 patients with melanoma and 10 subjects with normal skin. The quality and quantity of the RNA was determined and occludin expression level was measured using Real-time PCR and ∆∆CT computational technique. Results: Theoccludin mRNA level reduced five-fold in the melanoma patients compared to the control group (P=0.000). No significant difference was observed between male and female cases (P=0.533). No significant correlation was observed between occludin mRNA level, mitotic count (P=0.252), and Breslow levels (P=0.171) Conclusion: We can conclude that down-regulation of occludin expression in the patients with melanoma is a hallmark of cancer progression and it might be used as a prognostic factor. No significant correlation was found between occludin gene expression and clinicopathological characteristics including Clark level, Breslow staging, mitotic count, age and gender (P<0.05).

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 344
Author(s):  
Paul Kubelac ◽  
Cornelia Braicu ◽  
Lajos Raduly ◽  
Paul Chiroi ◽  
Andreea Nutu ◽  
...  

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression.


2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.


2019 ◽  
Vol 20 (17) ◽  
pp. 4156 ◽  
Author(s):  
Glatzel-Plucińska ◽  
Piotrowska ◽  
Dzięgiel ◽  
Podhorska-Okołów

Carcinogenesis is a long-drawn, multistep process, in which metastatic spread is an unequivocal hallmark of a poor prognosis. The progression and dissemination of epithelial cancers is commonly thought to rely on the epidermal-mesenchymal transition (EMT) process. During EMT, epithelial cells lose their junctions and apical-basal polarity, and they acquire a mesenchymal phenotype with its migratory and invasive capabilities. One of the proteins involved in cancer progression and EMT may be SATB1 (Special AT-Rich Binding Protein 1)—a chromatin organiser and a global transcriptional regulator. SATB1 organizes chromatin into spatial loops, providing a “docking site” necessary for the binding of further transcription factors and chromatin modifying enzymes. SATB1 has the ability to regulate whole sets of genes, even those located on distant chromosomes. SATB1 was found to be overexpressed in numerous malignancies, including lymphomas, breast, colorectal, prostate, liver, bladder and ovarian cancers. In the solid tumours, an elevated SATB1 level was observed to be associated with an aggressive phenotype, presence of lymph node, distant metastases, and a poor prognosis. In this review, we briefly describe the prognostic significance of SATB1 expression in most common human cancers, and analyse its impact on EMT and metastasis.


2020 ◽  
Author(s):  
Koichi Sato ◽  
Takeshi Uehara ◽  
Mai Iwaya ◽  
Tomoyuki Nakajima ◽  
Yosuke Tobe ◽  
...  

Abstract Background: Interleukin-6 (IL6) is one of the main cytokines produced by cancer-associated fibroblasts (CAFs). IL6 is linked with cancer progression and poor prognosis by activating cancer cells and modifying the cancer microenvironment. However, little is known about the expression of IL6 in tumor budding (TB) and its association with TB in colon adenocarcinoma (CA). Methods: The clinicopathological and prognostic significance of IL6 in TB was examined using a tissue microarray consisting of 36 patient samples of TB in CA. IL6 mRNA was detected by RNAscope kit. Patients were stratified into negative and positive IL6 expression groups.Results: IL6 expression was overwhelmingly observed in CAFs but was negligible in cancer cells. In the IL6-positive group in CAFs, TB grade was higher than in the IL6-negative group (P=0.0161). There was a significant difference in overall survival (OS) between CA cases in the IL6-positive group and the IL6-negative group (log rank test, P=0.0367). Cox proportional hazard regression model revealed that the IL6-negative group (OR = 0.25; 95% CI: 0.05–0.96; P=0.0440) had better OS for CA than the IL6-positive group. Conclusions: TB may be affected by IL6 expression, and IL6 expression in CAFs at TB may make IL6 an important prognostic marker.


2020 ◽  
Author(s):  
Mei Du ◽  
Piping Gong ◽  
Yun Zhang ◽  
Yanguo Liu ◽  
Xiaozhen Liu ◽  
...  

Abstract Lung cancer is the leading cause of cancer-related death worldwide, with an estimated 1.2 million deaths each year. Despite advances in lung cancer treatment, 5-year survival rates are lower than ~15%, which is attributes to diagnosis limitations and current clinical drug resistance. Recently, more evidence has suggested that epigenome dysregulation is associated with the initiation and progress of cancer, and targeting epigenome-related molecules improves cancer symptoms. Interestingly, some groups reported that the level of methylation of histone 3 lysine 4 (H3K4me3) was increased in lung tumors and participated in abnormal transcriptional regulation. However, a mechanistic analysis is not available. In this report, we found that the SET domain containing 1A (SETD1A), the enzyme for H3K4me3, was elevated in lung cancer tissue compared to normal lung tissue. Knockdown of SETD1A in A549 and H1299 cells led to defects in cell proliferation and epithelial-mesenchymal transition (EMT), as evidenced by inhibited WNT and TGFβ pathways, compared with the control group. Xenograft assays also revealed a decreased tumor growth and EMT in the SETD1A silenced group compared with the control group. Mechanistic analysis suggested that SETD1A might regulate tumor progression via several critical oncogenes, which exhibited enhanced H3K4me3 levels around transcriptional start sites in lung cancer. This study illustrates the important role of SETD1A in lung cancer and provides a potential drug target for treatment.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaian Tavakolian ◽  
Hossein Goudarzi ◽  
Ebrahim Faghihloo

Abstract Objective Breast cancer is one of the most common health problems. It has been suggested that several risk factors, either considered as external or internal, play a critical role in the pathogenesis of breast cancer, which among them, HERV-k, has the most fundamental role. In the present study, we aimed to evaluate the role of HERV-k env, gag, rec, np9 expressions in breast cancer progression. Materials and methods We collected 40 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV-k env, gag, rec, np9 by using Quantitative real-time PCR (qRT-PCR). Results The resulting data revealed that while there was a meaningful increase in the expression level of HERV-k env, gag and np9 in breast cancer tissues (P ≤ 0.01, 0.05, 0.05, respectively), we failed to find any significant elevation in the expression level of rec mRNA level. Conclusion The results of our study suggested that there is a plausible correlation between the mRNA expression level of HERV-K env, gag and np9 and the progression of breast cancer, proposing these markers as promising biomarkers to diagnose breast cancer.


2016 ◽  
Vol 28 (2) ◽  
pp. 199
Author(s):  
J. Guo ◽  
T. Kim ◽  
N.-H. Kim ◽  
X.-S. Cui

Liver receptor homolog 1 (LRH1, NR5A2) belongs to the orphan nuclear receptor superfamily and has diverse functions in development, differentiation, metabolism, and cell death. The LRH1 gene is expressed in embryonic stem cells and regulates the expression of OCT4, which is the key factor required to maintain pluripotency. However, the function of LRH1 in early porcine embryo development is still unknown. In the present study, we examined the localization and mRNA level of LRH1 in porcine parthenotes by immunofluorescence and real-time RT-qPCR. To explore the function of LRH1, the embryos were treated with the specific antagonist of LRH1, 505601, which is a cell-permeable pyrazolylbiphenylethanone compound that targets LRH-1/NR5A2 ligand binding domain (LBD) via direct affinity interaction, preventing LRH-1 from assuming an active conformation. Every group contained 20 embryos. The results showed that the immunofluorescence signal of LRH1 was only observed in nuclei of blastocyst cells. Inhibition of LRH1 by antagonist significantly (P < 0.05) reduced the blastocyst rate in the 50 µM (37.30 ± 3.67%) and 100 µM (38.02 ± 5.12%) treatment groups compared with the control group (53.43 ± 3.67%). The hatching rate of blastocysts was also reduced (P < 0.01) by 50 µM (12.66 ± 3.13%) and 100 µM (20.10 ± 2.81%) antagonist compared with control (40.59 ± 0.59%), which resulted from the decreased (P < 0.05) expression of hatching-related genes, such as FN1, ITGA5, and COX2. Inhibition of LRH1 also increased (P < 0.05) the number of apoptotic cells in blastocysts. Moreover, inhibition enhanced expression of apoptotic genes, BAX and CASP3, and reduced the anti-apoptosis gene BCL2 (P < 0.05). Messenger RNA and protein level of OCT4 were sharply decreased in blastocysts after LRH1 inhibition. All data were analysed with a one-way ANOVA, and differences between treatment groups were assessed by the least significant difference (LSD) test using SPSS software (SPSS Inc., Chicago, IL, USA). In conclusion, LRH1 affects blastocyst formation and hatching by regulating OCT4 expression and cell apoptosis.


2014 ◽  
Vol 26 (1) ◽  
pp. 212 ◽  
Author(s):  
F. Lu ◽  
Y. Lao ◽  
H. Sun ◽  
C. Lei ◽  
Y. Deng ◽  
...  

In this study, to explore the effects and mechanism of Wnt/β-catenin signalling pathway on the maintenance of pluripotency of buffalo embryonic stem-cell-like cells (buffalo ESC-like cells), the GSK3 inhibitors BIO and CHIR99021 were added throughout the experiment – i.e. from buffalo inner cell mass (ICM) culture to ESC-like line generation. The buffalo ICM were respectively cultured in the medium containing 0.5 μg mL–1 BIO and 5 mmol L–1 CHIR99021. The percentage of ICMs attachment and primary colony formation were observed, and found that there was no significant difference in the ICMs attachment rate among of the BIO, CHIR99021, and the control groups (91.18% and 92.98% v. 94.59%; P > 0.05). Treating ICMs with CHIR99021 resulted in more primary colony formation rate compared with the control group (77.71% v. 55.41%; P < 0.05). The proliferation rate of primary colonies of buffalo ESC-like cells was detected by bromodeoxyuridine immunofluorescence techniques. The results show that the proliferation rate of primary colonies in the group of buffalo ESC-like cells treated with CHIR99021 was significantly higher than that of the control group on Day 1, Day 3, Day 4, and Day 5 (P < 0.05), and it was also evidently higher than that of control group only on Day 1 (P < 0.05) in the group of BIO, but there was no significant difference in other days (P > 0.05). The mRNA expression level of proliferation marker PCNA of ESC-like cells was significantly up-regulated in both CHIR99021 and BIO treatment groups (P < 0.05), however, treating buffalo ESC-like cells with CHIR99021 significantly up-regulated the expression of pluripotent gene Oct4 and Sox2 (P < 0.05), but had no effect on pluripotent gene Nanog expression (P > 0.05). Oct4 expression was significantly increased (P < 0.05), and the expression of Sox2 and Nanog were significantly decreased (P < 0.05) in the group of BIO treatment. Furthermore, the relative protein level of β-catenin (the downstream effector of Wnt/β-catenin signalling pathway) and the mRNA expression level of c-Myc (the downstream target gene of Wnt/β-catenin signalling pathway) were significantly increased when buffalo ESC-like cells respectively treated with CHIR99021 and BIO (P < 0.05). In conclusion, treating buffalo ESC-like cells with GSK3 inhibitors CHIR99021 can promote proliferation of buffalo ESC-like cells, maintain their undifferentiated state, and up-regulate the expression levels of β-Catenin and c-Myc in buffalo ESC-like cells. These results indicate that Wnt/β-catenin signalling pathway plays an important role in regulation of self-renewal of buffalo ESC-like cells. This work was funded by the China High Technology Development Program (2011AA100607), China Natural Science Foundation (31072033), and Guangxi Science Foundation (2012GXNSFFA060004).


2020 ◽  
Vol 20 (6) ◽  
pp. 878-886
Author(s):  
Sobhan Helbi ◽  
Behnam Ravanbakhsh ◽  
Mohammad Karimi ◽  
Wesam Kooti ◽  
Nahid Jivad

Objective: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients’ treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients’ blood under a different type of IFNβ treatment. Methods: In the present study, 99 individuals participated. The participants were divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNβ-1a (B1a), 21 RRMS patients treated with IFNβ-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted into cDNA. To evaluate the expression of IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed done. The level of genes expression was measured using 2–ΔΔCt method. The obtained data were analyzed using SPSS v22 software. Results: Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant differences (p>0.05). Also, the evaluation of IFI16 mRNA level revealed that the IFI16 genes’ expressions were remarkably higher in the new case group compared to the control group, however, STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNβ-treated groups were significantly lower than the new case group (p<0.001). Also, the genes’ expressions in both the IFNβ-treated groups were significantly lower compared to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions with age and sex in different research groups, no statistically significant differences were seen (p>0.05). Conclusion: Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STINGdependent pathway as a negative feedback mechanism for regulation of the immune system and suppression of pro-inflammatory cytokines production. The important role of DNA sensing molecules and STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct therapies.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Himri Sara ◽  
Oumokhtar Bouchra ◽  
El Fakir Samira ◽  
Atmani Samir

Abstract Background The assay of antistreptolysin O antibodies “ASLO” can provide evidence of infection of streptococcal origin, but it cannot confirm the presence of rheumatic fever “RAA” or the degree of severity of the disease. However, it is widely prescribed in daily practice by pediatricians and general practitioners to diagnose RAA. Unfortunately, the only finding of a high rate of ASLO in front of recurrent tonsillitis in children is considered by some practitioners as sufficient evidence to support the diagnosis of RAA, especially in its minor form, without taking into account the Jones criteria. The objective of this study is to put the ASLO assay in its place in the diagnosis of RAA in children in the region of Fez in Morocco. Methods This is a prospective study carried out from January 2016 to July 2019 in the cardiopediatric unit of CHU Hassan II in Fez. Patients below 18 years of age were included in this study. The children are classified into 4 groups: group 1: RAA with cardiac involvement, group 2: RAA without cardiac involvement, group 3: recurrent pharyngitis and group 4: control. Children with RAA are diagnosed according to the modified Jones criteria. The repetitive angina group includes any child who has tonsillitis &gt;5 times a year. The control group presents healthy children. The ASLO assay was carried out in the central analysis laboratory of the CHU Hassan II in Fez. Patient data is collected on operating sheets. Statistical analysis was performed using SPSS v 21 software. Results These are 153 children with RAA: 119 cases of RAA with cardiac involvement and 34 cases of RAA without cardiac involvement, 86 children with recurrent pharyngitis and 157 children controls. The most common age group in the four groups is the age group between 5 and 15 years old. The frequency of children of urban origin is greater than that of rural origin in all the groups studied. The average ASLO rates in each group are as follows: RAA with carditis: 281.1 IU/ml RAA without carditis: 331.9 IU/ml Repeated angina: 397.7 IU/ml Control: 208.8 IU/ml Monitoring the change in ASLO, every 3 months for a year, in the groups studied showed that the ASLO level is stable at high rates in the case of recurrent pharyngitis and it tends to decrease in the case of AAR. Regarding the relationship between ASLO means and gender, there is a high ASLO mean in boys more than girls in all groups. Also, the mean ASLO is high in children from urban areas for the recurrent angina group. In addition, the average rate of ASLO is high during cold seasons in all groups. Finally, our study shows that the increase in ASLO is related to age. There is a significant difference between ASLO rates and age in all groups. Conclusion ASLO levels do not correlate with cardiac involvement but rather with infection and the child's individual immunity. The evidence is that ASLO levels&gt; 200 IU/ml are more common with recurrent pharyngitis than with rheumatic heart disease. So a high ASLO is not necessarily related to an RAA. Keywords ASLO, children, RAA, recurrent tonsillitis


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