| 1. |
- Acharjee, Animesh, et al.
(author)
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Immune infiltration and prognostic and diagnostic use of LGALS4 in colon adenocarcinoma and bladder urothelial carcinoma
- 2021
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In: American Journal of Translational Research. - : E-Century Publishing Corporation. - 1943-8141. ; 13:10, s. 11353-11363
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Journal article (peer-reviewed)abstract
- Colon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of colonic adenocarcinoma (COAD). We analysed 17 overlapping gene expression profiles of COAD and healthy samples obtained from TCGA-COAD and public single-cell sequencing resources, to identify potential therapeutic COAD targets. We evaluated the abundance of immune infiltration with those genes using the TIMER (Tumor Immune Estimation Resource) deconvolution method. Subsequently, we developed predictive and survival models to assess the prognostic value of these genes. The LGALS4 (Galectin-4) gene was found to be significantly (P<0.05) downregulated in COAD and bladder urothelial carcinoma (BLCA) compared to healthy samples. We identified LGALS4 as a prognostic and diagnostic marker for multiple cancer types, including COAD and BLCA. Our analysis reveals a series of novel candidate drug targets, as well as candidate molecular markers, that may explain the pathogenesis of COAD and BLCA. LGALS4 gene is associated with multiple cancer types and is a possible prognostic, as well as diagnostic, marker of COAD and BLCA.
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| 2. |
- Ageberg, Malin, et al.
(author)
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The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death.
- 2013
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In: American Journal of Translational Research. - 1943-8141. ; 5:2, s. 170-183
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Journal article (peer-reviewed)abstract
- Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.
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| 3. |
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| 4. |
- Feng, Yi, et al.
(author)
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Genetic modeling of ovarian phenotypes in mice for the study of human polycystic ovary syndrome
- 2013
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In: American journal of translational research. - 1943-8141. ; 5:1, s. 15-20
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Research review (peer-reviewed)abstract
- Abstract: Cladribine (2-CDA) is a well-known purine nucleoside analog with activities against lymphoproliferative disorders such as hairy cell leukemia (HCL). Bendamustine, a hybrid molecule of purine analog and alkylator, induces apoptosis via DNA damage response and inhibition of mitotic checkpoint. Their therapeutic potential in patients with multiple myeloma (MM), particularly those become resistant to traditional chemotherapeutic agents, remains unclear. Here we study the effects of cladribine or bendamustine on dexamethasone-sensitive (MM1.S) and -resistant (MM1.R) MM cells. MTS-based proliferation assays showed that cladribine and bendamustine exhibited similar anti-proliferation/anti-survival effects on MM1.S and MM1.R cells in a dose-dependent manner. The IC50s of cladribine were approximately 35.3 nmol/L and 58 nmol/L for MM1.S and MM1.R cells, respectively. The IC50s of bendamustine were approximately 119.8 μmol/L (MM1.S) and 138 μmol/L (MM1.R). An apoptotic- ELISA and western blot assays of PARP cleavage and activation of caspase-8 and caspase-3 indicated that cladribine or bendamustine induced apoptosis in both cell lines. Similar results were obtained with flow cytometric analysis showing that cladribine or bendamustine increased the sub-G1 population. Treatment with bendamustine but not cladribine also resulted in cell cycle S-phase arrest. Either cladribine or bendamustine led to a remarkable increase of the phosphorylated H2A.X, CHK1 and CHK2 in both MM1.S and MM1.R cells, suggesting an induction of DNA damage response. Collectively, we demonstrate that cladribine and bendamustine exert potent inhibitory effects on dexamethasone-sensitive and -resistant MM cells in vitro. Our data suggest that MM patients, including those with dexamethasone resistance, may particularly benefit from cladribine or bendamustine. (AJTR1212001). Polycystic ovary syndrome (PCOS) presents with a range of clinical complications including
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| 5. |
- Hu, Min, et al.
(author)
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Endometrial progesterone receptor isoforms in women with polycystic ovary syndrome
- 2018
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In: American Journal of Translational Research. - 1943-8141. ; 10:8, s. 2696-2705
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Journal article (peer-reviewed)abstract
- Context: Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all reproductive-aged women and is often accompanied by endometrial progesterone (P4) resistance. Endometrial cells from PCOS patients display increased progesterone receptor (PGR) expression; however, in vivo knockout studies and in vitro experiments indicate the two PGR isoforms are not functionally equivalent. Objective: We aimed to compare endometrial PGR iso-form expression between non-PCOS and PCOS patients during the proliferative phase. Design: A case-control study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha (ERα), and markers of cell proliferation was determined by qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays. Patient(s): Patients were recruited and diagnosed with PCOS according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia (n = 11) and from PCOS patients with or without hyperplasia (n = 14). Result(s): Although the alteration of PGRB mRNA and protein expression was different, we found that PGRA mRNA and protein expression was higher in PCOS patients than non-PCOS patients. PGRA/B and PGRB were localized in both epithelial and stromal cells, with notable changes in the nuclei of epithelial and stromal cells. A similar expression pattern of ERα, vimentin and Ki-67, in association with an increased PGR expression, was observed in PCOS patients. Conclusion(s): These results demonstrated that elevated both PGR isoform expression depends on the presence of PCOS, and our data suggest that abnormal regulation of PGR isoforms is a pathological outcome of defective endometrium in PCOS patients.
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| 6. |
- Li, Xin, et al.
(author)
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Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action.
- 2015
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In: American journal of translational research. - 1943-8141. ; 7:3, s. 574-86
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Journal article (peer-reviewed)abstract
- Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network.
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| 7. |
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| 8. |
- Shao, Linus Ruijin, 1964, et al.
(author)
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The elusive and controversial roles of estrogen and progesterone receptors in human endometriosis
- 2014
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In: American Journal of Translational Research. - 1943-8141. ; 6:2, s. 104-113
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Journal article (peer-reviewed)abstract
- Endometriosis is a complex and challenging disease that involves aberrant adhesion, growth, and progression of endometrial tissues outside of the uterine cavity, and there is evidence to suggest that estrogen plays a key role in its development and progression. Numerous in vivo clinical studies have described the ectopic expression and regulation of estrogen receptor (ER) and progesterone receptor (PR) in the different types of endometriosis compared to normal or eutopic endometrium. However, we have noticed that conflicting and contradictory results have been presented in terms of ER subtype (ERα and ERβ) and PR isoform (PRA and PRB) expression. Both ER and PR are transcription factors and ER/PR-mediated responses depend on the coordinated, opposing, and compensatory functions of ER subtypes and PR isoforms. Moreover, analysis of the uterine phenotypes of ERα/ERβ and PRA/PRB knockout mice indicates that different ER subtypes and PR isoforms mediate distinct responses to steroid hormones and play different roles in uterine function. In this review, we outline studies that have elucidated the molecules and signaling pathways that are linked to ER and/or PR signaling pathways in the development and progression of endometriosis.
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| 9. |
- Shao, Linus Ruijin, 1964, et al.
(author)
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The role of estrogen in the pathophysiology of tubal ectopic pregnancy
- 2012
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In: American Journal of Translational Research. - 1943-8141. ; 4:3, s. 269-278
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Journal article (peer-reviewed)abstract
- 17β-estradiol, acting through estrogen receptors α and β, plays a fundamental role in the regulation of Fallopian tube cell homeostasis and in the modulation of normal tubal physiological processes. Fluctuations in E2 levels also play crucial roles in the initiation or progression of numerous human diseases. Fallopian tube malfunction often results in tubal ectopic pregnancy, which is one cause of maternal morbidity and mortality in women. Several factors have been proposed to be associated with increased risk of tubal ectopic pregnancy, but whether these factors are the cause of, or are merely symptoms of, such pregnancies remains unresolved due to the lack of knowledge in regards to the mechanisms by which embryos inadvertently implant in the Fallopian tube. This review summarizes recent findings, including data from our own laboratory, on E2 metabolism and estrogen receptor (ER) subtype expression within the Fallopian tube in humans and rodents. This review also outlines several important, unresolved questions in the field that, once addressed, could offer important clues into how E2/ER signaling contributes to the pathology of tubal function. A better understanding of the specific functions of estrogen receptor subtypes in vivo, as well as of the mechanism and consequences of receptor subtype interactions is critical to understanding their respective roles in Fallopian tube physiology and in the pathophysiology and etiology of tubal ectopic pregnancy.
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| 10. |
- Wang, Lei, et al.
(author)
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Linking DNA methylation to the onset of human tubal ectopic pregnancy.
- 2013
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In: American journal of translational research. - 1943-8141. ; 5:2, s. 116-25
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Journal article (peer-reviewed)abstract
- Ectopic pregnancy is a common reproductive disorder of unknown etiology and is a leading cause of maternal and fetal mortality. Because of the asymptomatic nature of early tubal ectopic pregnancy and the lack of specific biomarkers for early diagnosis, a better understanding of the complex cellular and molecular interactions that contribute to tubal ectopic pregnancy is required. DNA methylation is the most studied epigenetic process in various tissues and cells, and the goal of this article is to provide a brief review of recent work describing the potential mechanisms of DNA methylation and the biological function of such methylation in normal intrauterine pregnancy. Further, novel findings from our laboratory highlight the possible role of DNA methylation in human Fallopian tube dysfunction and suggest a possible correlation between methylation of estrogen receptor α in women and the occurrence of tubal ectopic pregnancies.
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| 11. |
- Xu, Lili, et al.
(author)
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Cytokine dysregulation associated with malarial anemia in Plasmodium yoelii infected mice
- 2013
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In: American Journal of Translational Research. - 1943-8141. ; 5:2, s. 235-245
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Journal article (peer-reviewed)abstract
- The mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. Hematopoiesis is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. The present study used the murine P. yoelii 17XNL malaria model to investigate the profile of cytokines and leukocytes throughout the entire infection. Moreover, malaria induced anemia was studied in comparison with anemia induced by hemorrhage and hemolysis. During the P. yoelii infection, the levels of erythropoietic-related cytokines, such as G-CSF, GMCSF, IL-7, and IL-17, were pronouncedly reduced, while those of regulatory cytokines, such as IL-10 and TNF-alpha, were constantly increased. This cytokine profile corresponded well with the cellular composition during the infection, such as drastically decreased levels of CD4(+) and CD8(+) T cells. The profiles of erythropoiesis or hematopoiesis related cytokines during malarial anemia showed striking differences from those during anemia induced by hemorrhage or hemolysis. This study demonstrates that a markedly dysregulated cytokine network occurred in this murine malaria model, which may open a new window of insight into the mechanisms of malaria related anemia.
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| 12. |
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