This study is to identify potential multiomics biomarkers for the early detection of the prognostic recurrence of PC patients. A total of 494 prostate adenocarcinoma (PRAD) patients (60-recurrent ...included) from the Cancer Genome Atlas (TCGA) portal were analyzed using the autoencoder model and similarity network fusion. Then, multiomics panels were constructed according to the intersected omics biomarkers identified from the two models. Six intersected omics biomarkers, TELO2, ZMYND19, miR-143, miR-378a, cg00687383 (MED4), and cg02318866 (JMJD6; METTL23), were collected for multiomics panel construction. The difference between the Kaplan–Meier curves of high and low recurrence-risk groups generated from the multiomics panel achieved p-value = 5.33 × 10−9, which is better than the former study (p-value = 5 × 10−7). Additionally, when evaluating the selected multiomics biomarkers with clinical information (Gleason score, age, and cancer stage), a high-performance prediction model was generated with C-index = 0.713, p-value = 2.97 × 10−15, and AUC = 0.789. The risk score generated from the selected multiomics biomarkers worked as an effective indicator for the prediction of PRAD recurrence. This study helps us to understand the etiology and pathways of PRAD and further benefits both patients and physicians with potential prognostic biomarkers when making clinical decisions after surgical treatment.
A new pyrene derivative (
1) containing a diaminomaleonitrile moiety exhibits high selectivity for Cu
2+ detection. Significant fluorescence enhancement was observed with chemosensor
1 in the ...presence of Cu
2+. However, the metal ions Ag
+, Ca
2+, Cd
2+, Co
2+, Fe
2+, Fe
3+, Hg
2+, Mg
2+, Mn
2+, Ni
2+, Pb
2+, and Zn
2+ produced only minor changes in fluorescence values for the system. The apparent association constant (
K
a) of Cu
2+ binding in chemosensor
1 was found to be 5.55×10
3 M
−1. The maximum fluorescence enhancement caused by Cu
2+ binding in chemosensor
1 was observed over the pH range 5–7.5.
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Human urothelial carcinoma (UC) has a high tendency to recur and progress to life-threatening advanced diseases. Advanced therapeutic regimens are needed to control UC development and recurrence.
We ...pursued in vitro and in vivo studies to understand the ability of a triple combination of gemcitabine, romidepsin, and cisplatin (Gem+Rom+Cis) to modulate signalling pathways, cell death, drug resistance, and tumour development.
Our studies verified the ability of Gem+Rom+Cis to synergistically induce apoptotic cell death and reduce drug resistance in various UC cells. The ERK pathway and reactive oxygen species (ROS) played essential roles in mediating Gem+Rom+Cis-induced caspase activation, DNA oxidation and damage, glutathione reduction, and unfolded protein response. Gem+Rom+Cis preferentially induced death and reduced drug resistance in oncogenic H-Ras-expressing UC vs. counterpart cells that was associated with transcriptomic profiles related to ROS, cell death, and drug resistance. Our studies also verified the efficacy and safety of the Gem plus Rom+Cis regimen in controlling UC cell-derived xenograft tumour development and resistance.
More than 80% of UCs are associated with aberrant Ras-ERK pathway. Thus the compensatory combination of Rom with Gem and Cis should be seriously considered as an advanced regimen for treating advanced UCs, especially Ras-ERK-activated UCs.
Manual inspection and harvesting of ripening tomatoes is time consuming and labor intensive. Smart agriculture can emphasize the use of digital horticultural resources for farming and can increase ...farm sustainability; to that end, we proposed a fuzzy Mask R-CNN model to automatically identify the ripeness levels of cherry tomatoes. First, to annotate the images automatically, a fuzzy c-means model was used to maintain the spatial information of various foreground and background elements of the image. Then, a Hough transform method was applied to locate the specific geometric edge positions of the tomatoes. Each data point of the image space was annotated to a JavaScript Object Notation file. Second, annotated images were trained with Mask R-CNN to identify each tomato precisely. Finally, to prevent preharvest abscission of tomatoes, a hue-saturation-value color model and fuzzy inference rules were used to predict the ripeness of the tomatoes. A trigonometric function with Euclidian distance was calculated from the origin of calyx and stem to the bottom of the tomato to obtain the position of the pedicle head and dissect the fruit in a timely manner. For detection of 100 tomato images, Mask R-CNN achieved an accuracy of 98.00%. The ripeness classification of tomatoes achieved overall weighted precision and recall rates of 0.9614 and 0.9591, respectively. Thus, automatic tomato harvesting applications can empower farmers to make better decisions and enhance overall production efficiency and yield.
Using high-density oligonucleotide microarrays and functional network analyses, we examined whether MSCs derived from four different origins exhibited unique gene expression profiles individually and ...then compared the gene expression profiles of all MSCs with those of fetal organs. Our results indicated that within each group of MSCs from the same origin, the variability of the gene expression levels was smaller than that between groups of different origins. Functional genomic studies revealed the specific roles of MSCs from different origins. Our results suggest that amniotic fluid MSCs may initiate interactions with the uterus by upregulating oxytocin and thrombin receptors. Amniotic membrane MSCs may play a role in maintaining homeostasis of fluid and electrolytes by regulating the networks of endothelin, neprilysin, bradykinin receptors, and atrial natriuretic peptide. Cord blood MSCs may be involved in innate immune systems as the neonatal defense system against the earliest encountered pathogens. Adult bone marrow MSCs may be an important source not only of all blood lineages but also of bone formation. However, in spite of the different gene expression profiles seen in MSCs derived from different origins, a set of core gene expression profiles was preserved in these four kinds of MSCs. The core signature transcriptomes of all MSCs, when contrasted against those of fetal organs, included genes involved in the regulation of extracellular matrix and adhesion, transforming growth factor-beta receptor signaling, and the Wnt signaling pathways. Disclosure of potential conflicts of interest is found at the end of this article.
Indigo naturalis has been used to treat inflammatory diseases and dermatosis, including psoriasis, since thousands of years in China. It has been proven effective in our previous clinical studies on ...treating psoriasis, but the active component and the mechanism of how indigo naturalis working still needs to be clarified. Since the dysregulated angiogenesis is known to play an important role in the pathogenesis of psoriasis, the anti-angiogenic effect of indigo naturalis and tryptanthrin, a pure component of indigo naturalis, was investigated.
The in vivo angiogenesis was studied by chick chorioallantoic membrane assay. The in vitro studies were performed using human vascular endothelial cells. Cell viability was determined by MTT assay. Cell cycle distribution was revealed by flow cytometry. The cellular messenger (m)RNA or protein expression level was analyzed by real-time RT-PCR or Western blot, respectively. Transwell filter migration assay and matrix gel-induced tube formation method were applied to examine the angiogenic potential.
Indigo naturalis significantly inhibited the in vivo vascular endothelial growth factor (VEGF)-induced angiogenesis, as well as tryptanthrin. In vitro studies confirmed that indigo naturalis and tryptanthrin reduced the number of viable vascular endothelial cells. Tryptanthrin resulted in a cell cycle arrest and dose-dependently decreased the expressions of cyclin A, cyclin B, cyclin dependent kinase(CDK) 1 and 2, but not cyclin D and cyclin E, at both the mRNA and protein levels. The migration and tube formation of vascular endothelial cells were significantly inhibited by tryptanthrin in a dose-dependent manner. Result also showed that tryptanthrin could reduce the phosphorylated levels of both protein kinase B (PKB or Akt) and focal adhesion kinase (FAK).
All together, these results demonstrated the anti-angiogenic effect of tryptanthrin, the acting component of indigo naturalis and revealed the underlying mechanism by inhibiting the cell cycle progression, cell migration and tube formation, likely mediated through blocking the Akt and FAK pathways.
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Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of estrogen receptor (ER) through genomic and non-genomic mechanisms and are implicated in the development of endometrial ...cancer. Previous reports have demonstrated that estradiol and tamoxifen induce proliferation of human endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway. Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30 agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines with or without ERα (Ishikawa and RL95-2). Additionally, the GPR30-mediated cell migration was further abolished by administration of either specific RNA interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues with low or without ERα further suggested that estrogen-induced phosphorylation of FAK and cell migration were most likely triggered by GPR30 activation. These results provided new insights for understanding the pathophysiological functions of GPR30 in human endometrial cancers.
Calcaneal quantitative ultrasonography (QUS) is a useful prescreening tool for osteoporosis, while the dual-energy X-ray absorptiometry (DXA) is the mainstream in clinical practice. We evaluated the ...correlation between QUS and DXA in a Taiwanese population. A total of 772 patients were enrolled and demographic data were recorded with the QUS and DXA T-score over the hip and spine. The correlation coefficient of QUS with the DXA-hip was 0.171. For DXA-spine, it was 0.135 overall, 0.237 in females, and 0.255 in males. The logistic regression model using DXA-spine as a dependent variable was established, and the classification table showed 66.2% accuracy. A receiver operating characteristic (ROC) analyses with Youden's Index revealed the optimal cut-off point of QUS for predicting osteoporosis to be 2.72. This study showed a meaningful correlation between QUS and DXA in a Taiwanese population. Thus, it is important to pre-screen for osteoporosis with calcaneus QUS.
To evaluate the expression pattern of activins and related growth factor messenger RNA (mRNA) levels in adenomyotic nodules and in their endometrium.
Prospective study.
University hospital.
...Symptomatic premenopausal women scheduled to undergo hysterectomy for adenomyosis.
Samples from adenomyotic nodules and homologous endometria were collected. Endometrial tissue was also obtained from a control group.
Quantitative real-time polymerase chain reaction (PCR) analysis and immunohistochemical localization of activin-related growth factors (activin A, activin B, and myostatin), binding protein (follistatin), antagonists (inhibin-α, cripto), and receptors (ActRIIa, ActRIIb) were performed.
Myostatin mRNA levels in adenomyotic nodule were higher than in eutopic endometrium and myostatin, activin A, and follistatin concentrations were higher than in control endometrium. No difference was observed for inhibin-α, activin B, and cripto mRNA levels. Increased mRNA levels of ActRIIa and ActRIIb were observed in adenomyotic nodules compared with eutopic endometrium and control endometrium. Immunofluorescent staining for myostatin and follistatin confirmed higher protein expression in both glands and stroma of patients with adenomyosis than in controls.
The present study showed for the first time that adenomyotic tissues express high levels of myostatin, follistatin, and activin A (growth factors involved in proliferation, apoptosis, and angiogenesis). Increased expression of their receptors supports the hypothesis of a possible local effect of these growth factors in adenomyosis. The augmented expression of ActRIIa, ActRIIb, and follistatin in the endometrium of these patients may play a role in adenomyosis-related infertility.
Abstract Objectives Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and ...single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas. Methods Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays. Results Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors. Conclusion Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.
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