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Advances in Anatomic Pathology Sep 2022A variety of endometrial lesions may contain mucinous cells. Herein, the author reviews the literature on the classification and clinicopathologic significance of...
A variety of endometrial lesions may contain mucinous cells. Herein, the author reviews the literature on the classification and clinicopathologic significance of uterine corpus proliferations with a significant mucinous component, assesses the 2020 World Health Organization classification of such lesions, and presents a diagnostic framework. The key epithelial mucinous lesions include mucinous metaplasia, atypical mucinous glandular proliferation and mucinous carcinoma. Each of these categories are classifiable into "usual" and gastrointestinal subtypes, the latter being indicative of intestinal (presence of goblet cells) and/or gastric-type (abundant, pale eosinophilic or clear cytoplasm and well-defined cell borders) morphology. It has been proposed that at least focal expression of gastrointestinal immunohistochemical markers be required for all gastrointestinal type lesions, and for gastrointestinal type atypical mucinous glandular proliferation and carcinoma, minimality or absence of estrogen receptor expression, and the absence of an endometrioid component. Mucinous carcinomas of the usual type, in which >50% of the tumor is comprised of a mucinous component, are the most common. Morphologic subtypes include mucinous carcinoma with microglandular features and mucinous carcinoma with signet rings (signet ring carcinoma). Endometrioid carcinomas with a less than a 50% mucinous component are classified as endometrioid carcinoma with mucinous differentiation. Several studies have directly compared endometrioid and mucinous carcinomas, the latter presumably of the usual type, with respect to patient outcomes after treatment. All have found no difference in overall and disease free survival between these groups. However, three major studies have found mucinous carcinomas to be associated with a higher risk of lymph node metastases. Nineteen cases of mucinous carcinoma of the gastrointestinal type have been reported, and the limited data on their follow-up after primary treatment suggests that this subtype is more clinically aggressive and should accordingly be classified separately from mucinous carcinomas of the usual type. The morphologic spectrum of mucinous carcinoma of the gastrointestinal type is unclear and continues to evolve. Mucinous change, which may sometimes be extensive, may also be associated with papillary proliferation of the endometrium, adenomyoma of the endocervical type, atypical, and typical adenomyomas. In a curettage or biopsy, intestinal type mucinous epithelium may be indicative of any of the gastrointestinal lesions mentioned above, but may also represent samplings of uterine teratomas, yolk sac tumors, genital and extragenital adenocarcinomas with intestinal differentiation, or low-grade appendiceal mucinous neoplasms that secondarily involve the endometrium.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Carcinoma, Endometrioid; Endometrial Neoplasms; Endometrium; Female; Humans; Uterine Neoplasms
PubMed: 35499137
DOI: 10.1097/PAP.0000000000000348 -
Current Stem Cell Research & Therapy 2023Pulp regeneration is a promising strategy that promotes the continued development of young permanent teeth with immature apical foramen. Platelet-rich fibrin (PRF) was...
BACKGROUND
Pulp regeneration is a promising strategy that promotes the continued development of young permanent teeth with immature apical foramen. Platelet-rich fibrin (PRF) was found to stimulate the proliferation and differentiation of osteoblasts, but its effects on osteoblast/odontoblast differentiation of human dental pulp stem cells (hDPSCs) are unknown.
METHODS
The hDPSCs were isolated and identified using known surface markers by flow cytometry. The CCK-8 assay and the expression of Ki67 and PCNA were used to examine hDPSC proliferation. After 7 days of culture in an osteo-/odontoblastic induction medium with various concentrations of liquid PRF (0, 10% and 20%), the early stage of osteogenesis-intracellular alkaline phosphatase (ALP) was checked. After 21 days of culture, matrix mineralization was checked using Alizarin Red S and quantified. The mRNA and protein levels of osteo-/odontoblastic genes, including RUNX2, DSPP, DMP1 and BSP, were measured by qRT-PCR. The notch signal was checked by Western blot to analyze three key proteins (Notch 1, Jagged 1 and Hes 1).
RESULTS
PRF-treated groups showed higher expression of Ki-67 and PCNA, higher ALP activity, and the higher dose showed a stronger induction. PRF promoted osteo-/odontoblastic differentiation of hDPSCs indicated by elevated protein levels and mRNA levels of the expression of osteo-/odontoblastic markers. The three key proteins in Notch signaling showed an increase compared with the control group and increased as the PRF concentration increased.
CONCLUSION
PRF can promote the proliferation and osteo-/odontoblastic differentiation of hDPSC, which may be through the Notch signaling pathway.
Topics: Humans; Platelet-Rich Fibrin; Dental Pulp; Proliferating Cell Nuclear Antigen; Cell Proliferation; Regeneration; Cell Differentiation; Stem Cells; Cells, Cultured; Odontoblasts
PubMed: 35794740
DOI: 10.2174/1574888X17666220704092411 -
European Journal of Histochemistry : EJH Oct 2023Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways....
Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.
Topics: Animals; Rats; Bile Ducts; Brain-Derived Neurotrophic Factor; Cell Proliferation; Epithelium; Nerve Tissue Proteins
PubMed: 37859350
DOI: 10.4081/ejh.2023.3846 -
Molecular Medicine Reports May 2023Nasopharyngeal carcinoma (NPC) is a primary malignancy that originates from the nasopharyngeal region. It has been demonstrated that a decrease in the expression level...
Nasopharyngeal carcinoma (NPC) is a primary malignancy that originates from the nasopharyngeal region. It has been demonstrated that a decrease in the expression level of cell division cycle gene 25A (CDC25A) suppresses cell viability and induces apoptosis in a variety of different types of cancer. However, at present, the role of CDC25A in NPC has yet to be fully elucidated. Therefore, the aim of the present study was to investigate the role of CDC25A in NPC progression and to explore the potential underlying mechanism. Reverse transcription‑quantitative PCR was performed to detect the relative mRNA levels of CDC25A and E2F transcription factor 1 (E2F1). Western blot analysis was subsequently used to determine the expression levels of CDC25A, Ki67, proliferating cell nuclear antigen (PCNA) and E2F1. CCK8 assay was employed to measure cell viability and flow cytometric analysis was employed to analyze the cell cycle. The binding sites between the CDC25A promoter and E2F1 were predicted using bioinformatics tools. Finally, luciferase reporter gene and chromatin immunoprecipitation assays were performed to verify the interaction between CDC25A and E2F1. The results obtained suggested that CDC25A is highly expressed in NPC cell lines and CDC25A silencing was found to inhibit cell proliferation, reduce the protein expression levels of Ki67 and PCNA and induce G1 arrest of NPC cells. Furthermore, E2F1 could bind CDC25A and positively regulate its expression at the transcriptional level. In addition, CDC25A silencing abolished the effects of E2F1 overexpression on cell proliferation and the cell cycle in NPC. Taken together, the findings of the present study showed that CDC25A silencing attenuated cell proliferation and induced cell cycle arrest in NPC and CDC25A was regulated by E2F1. Hence, CDC25A may be a promising therapeutic target for treatment of NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Proliferating Cell Nuclear Antigen; Genes, cdc; Ki-67 Antigen; Cell Line, Tumor; Cell Proliferation; Cell Cycle Checkpoints; Cell Cycle; Nasopharyngeal Neoplasms; Gene Expression Regulation, Neoplastic; cdc25 Phosphatases
PubMed: 37052240
DOI: 10.3892/mmr.2023.12996 -
Animals : An Open Access Journal From... Jul 2022The E2F family of transcription factor is divided into activators and repressors that control cell proliferation. Bovine mammary epithelial cells (BMECs) can be...
The E2F family of transcription factor is divided into activators and repressors that control cell proliferation. Bovine mammary epithelial cells (BMECs) can be immortalized using human papillomavirus 16 E6E7 (HPV16 E6E7) and simian vacuolating virus 40 large T antigen (SV40T). In addition, SV40T does not require E2F1, E2F2, and E2F3 activators to induce proliferation in mouse embryo fibroblasts (MEFs). However, we report that E2F3 activator is required to induce the proliferation of BMECs. Our results showed that, at an early stage, primary BMECs lacking the E2F1 expression have the capacity to proliferate and show E2F2 and E2F3 slight protein levels. At a late stage, primary BMECs deficient for E2F3 completely abolish any proliferative ability and exhibit a severe cell senescence signal, although the E2F2 can be expressed at a late stage of primary BMECs. Compared with the late stage of primary BMECs, the BMECs immortalized by SV40T and E6E7 restored the protein level of E2F3 and enhanced the CDK4, CDK6, cyclin D3, and CDK2 protein level, leading to proliferating robustly. Surprisingly, it was found that p53, p21, and p27 were upregulated in SV40T and E6E7-immortalized BMECs, relatively to primary BMECs. Notably, Cdc2 was almost expressed in primary BMECs. However, Cdc2 was elevated in BMECs immortalized by SV40T and E6E7. In conclusion, this study revealed a molecular mechanism where E2F3 controls the BMECs' proliferation and senescence.
PubMed: 35883337
DOI: 10.3390/ani12141790 -
Faculty Reviews 2023Cell proliferation control is essential during development and for maintaining adult tissues. Loss of that control promotes not only oncogenesis when cells proliferate... (Review)
Review
Cell proliferation control is essential during development and for maintaining adult tissues. Loss of that control promotes not only oncogenesis when cells proliferate inappropriately but also developmental abnormalities or degeneration when cells fail to proliferate when and where needed. To ensure that cells are produced at the right place and time, an intricate balance of pro-proliferative and anti-proliferative signals impacts the probability that cells undergo cell cycle exit to quiescence, or G phase. This brief review describes recent advances in our understanding of how and when quiescence is initiated and maintained in mammalian cells. We highlight the growing appreciation for quiescence as a collection of context-dependent distinct states.
PubMed: 36923701
DOI: 10.12703/r/12-5 -
LINC00106/RPS19BP1/p53 axis promotes the proliferation and migration of human prostate cancer cells.PeerJ 2023Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular...
BACKGROUND
Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular carcinoma (HCC). However, it is unclear how it affects PCa advancement. Here, we studied LINC00106's effects on PCa cells' ability to proliferate, invade, and metastasize.
METHODS
The data of LINC00106 from The Cancer Genome Atlas (TCGA) in human PCa tissues were analyzed using TANRIC and survival analysis. In order to determine the expression levels of genes and proteins, we also performed reverse transcription-quantitative PCR and western blot analysis. The migration, invasion, colony formation, and proliferation (CCK-8) of PCa cells with LINC00106 knockdown were investigated. The impact of LINC00106 on cell proliferation and invasion was also analyzed in mice. LncRNA prediction software catRAPID omics v2.1 (catRAPID omics v2.0 (tartaglialab.com)) was used to predict proteins that might interact with LINC00106. The interactions were verified via RNA immunoprecipitation and RNA pull-down assays and finally, the interaction between LINC00106 and its target protein and the p53 signaling pathway was studied using a dual-luciferase reporter assay.
RESULTS
In PCa, LINC00106 was over-expressed in comparison to normal tissues, and it was linked to an unfavorableprognosis. and analyses showed that downregulating LINC00106 decreased PCa cells'ability to proliferate and migrate. A common regulatory axis generated by LINC00106 and RPS19BP1 prevents p53 activity.
CONCLUSION
Our experimental data indicate that LINC00106 functions as an oncogene in the onset of PCa, and the LINC00106/RPS19BP1/P53 axis canserve as a novel therapeutic target for PCa treatment.
Topics: Male; Humans; Animals; Mice; Tumor Suppressor Protein p53; Carcinoma, Hepatocellular; Liver Neoplasms; Prostatic Neoplasms; MicroRNAs; Cell Proliferation
PubMed: 37180577
DOI: 10.7717/peerj.15232 -
Medical Archives (Sarajevo, Bosnia and... Aug 2021Recent advances in stem cell technologies have rekindled an interest in the use of cell therapies to treat patients with Parkinson's disease. Although the...
BACKGROUND
Recent advances in stem cell technologies have rekindled an interest in the use of cell therapies to treat patients with Parkinson's disease. Although the transplantation of dopaminergic mesencephalic human fetal brain tissue has previously been reported in the treatment of patients with Parkinson's disease, this method is limited by the availability of tissue obtained from each human embryo.
OBJECTIVE
Our study aimed to isolate, culture, proliferate, and differentiate dopaminergic neurons from human neuroepithelial stem cells obtained from embryo reduction procedures performed in multifetal pregnancies following in vitro fertilization.
MATERIALS AND METHODS
A total of 201 human embryos were dissected for isolation and culture of neuroepithelial stem cells for proliferation and differentiation into dopaminergic neurons. All embryos were obtained from embryo reduction procedures performed in multifetal pregnancies after in vitro fertilization treatments.
RESULTS
Human neuroepithelial stem cells were isolated and cultured from embryos from 6.0 to 8.0 weeks. Neuroepithelial stem cells were successfully isolated, proliferated, and differentiated into dopaminergic neurons. The cells adhered to the surfaces of cell culture plates after 2 days and could be proliferated and differentiated into neurons within 4 days. Cultured cells expressed the dopaminergic marker tyrosine hydroxylase after 6 days, suggesting that these cells were successfully differentiated into dopaminergic neurons.
CONCLUSION
The successful isolation, culture, proliferation, and differentiation of human dopaminergic neurons from embryo reductions performed for multifetal pregnancies after in vitro fertilization suggests that this pathway may serve as a potential source of cell therapy materials for use in the treatment of Parkinson's disease.
Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Dopaminergic Neurons; Female; Fertilization in Vitro; Humans; Pregnancy; Pregnancy Reduction, Multifetal; Stem Cells
PubMed: 34759448
DOI: 10.5455/medarh.2021.75.280-285 -
Frontiers in Neuroscience 2020Astrocytes exhibit a region-dependent molecular and functional heterogeneity in the CNS. Although cortical astrocytes proliferate robustly during the first postnatal...
Astrocytes exhibit a region-dependent molecular and functional heterogeneity in the CNS. Although cortical astrocytes proliferate robustly during the first postnatal week and become proliferation quiescent, the temporal proliferation dynamics of astrocytes in subcortical regions during postnatal development remain essentially unknown. Whether subcortical astrocytes mature similarly to cortical astrocytes is also unexplored. In this current study, we examined proliferation of subcortical, especially hypothalamic, astrocytes during postnatal development using genetic labeling of astrocytes and pulse-chase EdU labeling of proliferating cells. While a lower number of proliferating astrocytes was found in the hypothalamus compared to cortex during the first postnatal week, astrocyte proliferation is much more active in hypothalamus than in cortex from P15 to P30 in both proliferating astrocyte density and percentage, indicating a persistent and distinct proliferation pattern of astrocytes in hypothalamus. This observation is further confirmed by Ki67 immunostaining with genetically or immunolabeled astrocytes in hypothalamus and cortex during P15-30. In addition, astrocytes in representative subcortical regions have a modest growth of their domain size and exhibit a significantly smaller domain size compared to cortical astrocytes at P30 when astrocytes have generally completed postnatal maturation. However, the expression of astrocyte-derived Sparc, an important synaptogenic inhibitor, is consistently higher in hypothalamic astrocytes than in cortical astrocytes throughout postnatal development. In summary, our study unveiled a distinct proliferation and maturation pattern of subcortical, especially hypothalamic, astrocytes during postnatal development.
PubMed: 32457572
DOI: 10.3389/fnins.2020.00435 -
Frontiers in Cell and Developmental... 2022Stem Leydig cells (SLCs) play a critical role in the development and maintenance of the adult Leydig cell (ALC) population. SLCs also are present in the adult testis....
Stem Leydig cells (SLCs) play a critical role in the development and maintenance of the adult Leydig cell (ALC) population. SLCs also are present in the adult testis. Their identification, characteristics, and regulation in the adult testis remain uncertain. Using single-cell RNA-seq, we found that the mesenchymal stromal population may be involved in ALC regeneration. Upon ALC elimination, a fraction of stromal cells begins to proliferate while a different fraction begins to differentiate to ALCs. Transcriptomic analysis identified five stromal clusters that can be classified into two major groups representing proliferation and differentiation populations. The proliferating group represents stem cells expressing high levels of CD90, Nes, Lum, Fn and Gap43. The differentiating group represents a progenitor stage that is ready to form ALCs, and specifically expresses Vtn, Rasl11a, Id1 and Egr2. The observation that the actively dividing cells after ALC loss were not those that formed ALCs suggests that stem cell proliferation and differentiation are regulated separately, and that the maintenance of the stromal stem cell pool occurs at the population level. The study also identified specific markers for the major interstitial cell groups and potential paracrine factors involved in the regulation of SLCs. Our data suggest a new theory about SLC identity, proliferation, differentiation, and regulation.
PubMed: 35242757
DOI: 10.3389/fcell.2022.805249