scholarly journals Differentiation potential to neural-like cells in human adrenocortical carcinoma SW-13 cells

2019 ◽  
Author(s):  
Eriko Shimada ◽  
Yusuke Tsuruwaka
Keyword(s):  
Early Diagnosis ◽  
Adrenal Gland ◽  
Cancer Cells ◽  
Adrenocortical Carcinoma ◽  
Neural Differentiation ◽  
Neural Induction ◽  
Carcinoma Cells ◽  
Rare Cancer ◽  
Differentiation Potential ◽  
Aggressive Tumor

Various cancer cells are known to show neural differentiation. Adrenocortical carcinoma (ACC) is a rare and frequently aggressive tumor originating in the cortex of the adrenal gland. Early diagnosis of ACC is challenging due to a lot of unknown aspects such as cell characteristics in a rare cancer. In the present study, morphological features were examined in the adrenal cortex carcinoma cells SW-13 as an initial candidate, which were exposed to neural differentiation condition. SW-13 cells treated with the neural induction supplement showed neural-like differentiation with elongated filaments. It was suggested that SW-13 cells had neural differentiation potential and could be a research tool to elucidate the cell characteristics in future ACC studies.

scholarly journals Differentiation potential to neural-like cells in human adrenocortical carcinoma SW-13 cells

2019 ◽  
Author(s):  
Eriko Shimada ◽  
Yusuke Tsuruwaka
Keyword(s):  
Early Diagnosis ◽  
Adrenal Gland ◽  
Cancer Cells ◽  
Adrenocortical Carcinoma ◽  
Neural Differentiation ◽  
Neural Induction ◽  
Carcinoma Cells ◽  
Rare Cancer ◽  
Differentiation Potential ◽  
Aggressive Tumor

Various cancer cells are known to show neural differentiation. Adrenocortical carcinoma (ACC) is a rare and frequently aggressive tumor originating in the cortex of the adrenal gland. Early diagnosis of ACC is challenging due to a lot of unknown aspects such as cell characteristics in a rare cancer. In the present study, morphological features were examined in the adrenal cortex carcinoma cells SW-13 as an initial candidate, which were exposed to neural differentiation condition. SW-13 cells treated with the neural induction supplement showed neural-like differentiation with elongated filaments. It was suggested that SW-13 cells had neural differentiation potential and could be a research tool to elucidate the cell characteristics in future ACC studies.

191 ROBUST GENERATION OF NEURAL STEM CELLS FROM PIG INDUCED PLURIPOTENT STEM CELLS FOR TRANSLATIONAL NEURAL REGENERATIVE MEDICINE

2014 ◽  
Vol 26 (1) ◽  
pp. 210
Author(s):  
A. Gallegos-Cardenas ◽  
K. Wang ◽  
E. T. Jordan ◽  
R. West ◽  
F. D. West ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Differentiation ◽  
Neural Induction ◽  
Differentiation Potential ◽  
Induced Pluripotent ◽  
Human Ipsc

The generation of pig induced pluripotent stem cells (iPSC) opened the possibility to evaluate autologous neural cell therapy as a viable option for human patients. However, it is necessary to demonstrate whether pig iPSC are capable of in vitro neural differentiation similar to human iPSC in order to perform in vitro and in vivo comparative studies. Multiple laboratories have generated pig iPSC that have been characterised using pluripotent markers such as SSEA4 and POU5F1. However, correlations of pluripotent marker expression profiles among iPSC lines and their neural differentiation potential has not been fully explored. Because neural rosettes (NR) are composed of neural stem cells, our goal was to demonstrate that NR from pig iPSC can be generated, isolated, and expanded in vitro from multiple porcine iPSC lines similar to human iPSC and that the level of pluripotency in the starting porcine iPSC population (POUF51 and SSEA4 expression) could influence NRs development. Three lines of pig iPSC L1, L2, and L3 were cultured on matrigel-coated plates in mTeSR1 medium (Stemcell Technologies Inc., Vancouver, BC, Canada) and passaged every 3 to 4 days. For neural induction (NI), pig iPSC were disaggregated using dispase and plated. After 24 h, cells were maintained in N2 media [77% DMEM/F12, 10 ng mL–1 bovine fibroblast growth factor (bFGF), and 1X N2] for 15 days. To evaluate the differentiation potential to neuron and glial cells, NR were isolated, expanded in vitro and cultured for three weeks in AB2 medium (AB2, 1X ANS, and 2 mM L-Glutamine). Immunostaining assays were performed to determine pluripotent (POU5F1 and SSEA4), tight junction (ZO1), neural epithelial (Pax6 and Sox1), neuron (Tuj1), astrocyte (GFAP), and oligodendrocyte (O4) marker expression. Line L2 (POU5F1high and SSEA4low) showed a high potential to form NR (6.3.5%, P < 0.05) in comparison to the other 2 lines L1 (POU5F1low and SSEA4low) and L3 (POU5F1low and SSEA4high) upon NI. The NR immunocytochemistry results from Line L2 showed the presence of Pax6+ and Sox1– NRs cells at day 9 post-neural induction and that ZO1 started to localise at the apical border of NRs. At day 13, NRs cells were Pax6+ and Sox1+, and ZO1 was localised to the lumen of NR. After isolation and culture in vitro, NR cells expressed transcription factors PLAGL1, DACH1, and OTX2 through 2 passages, but were not detected in later passages. However, rosette cytoarchitecture was present up until passage 7 and were still Pax6+/Sox1+. NRs at passage 2 were cryopreserved and upon thaw showed normal NR morphology and were Pax6+/Sox1+. To characterise the plasticity of NRs, cells were differentiated. Tuj1 expression was predominant after differentiation indicating a bias towards a neuron phenotype. These results demonstrate that L2 pig iPSC (POUF51high and SSEA4low) have a high potential to form NR and neural differentiation parallels human iPSC neurulation events. Porcine iPSC should be considered as a large animal model for determining the safety and efficacy of human iPSC neural cell therapies.

scholarly journals MON-LB037 Adrenocortical Carcinoma: A Case Report

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Farha Naz Ebadi ◽  
Marcus Karim ◽  
Kenneth Chen ◽  
Reshma Abraham
Keyword(s):  
Adrenal Gland ◽  
Lower Extremity ◽  
Adrenocortical Carcinoma ◽  
Lung Metastases ◽  
Gastroesophageal Junction ◽  
Survival Rates ◽  
Adrenal Tumors ◽  
Bilateral Lower Extremity ◽  
Polysubstance Use ◽  
Aggressive Tumor

Abstract Introduction: Unilateral adrenal tumors are relatively common; adrenal incidentaloma has a prevalence of 4% on CT imaging. These masses are classified by their functional and malignant potential. We present here a case of adrenocortical carcinoma (ACC), a rare and often aggressive tumor that accounts for 2% of all adrenal incidentalomas. ACC has a worldwide incidence of disease of 0.5-2 cases per million population per year. While some instances of ACC are associated with hereditary conditions, most cases are sporadic mutations. Case: A 44-year-old male with a past medical history of hypertension, polysubstance use, and anasarca presented with a one-year onset of abdominal swelling. This was associated with a 16 pound weight loss over the prior 4 months and bilateral lower extremity swelling for the previous 3 weeks. Of note the patient had been detained in an adult corrections institution for over 5 years. Review of systems was negative for night sweats, nausea, vomiting, headaches, confusion, or palpitations. CT of the abdomen demonstrated a large mass involving the left adrenal gland measuring 28 x 27 x 31 cm, with punctate and delayed calcifications. Also noted were numerous bilateral lung nodules, and multiple liver lesions. Bilateral lower extremity ultrasound revealed a DVT involving the left gastrocnemius vein. A heparin drip was initiated and the patient was transitioned to Xarelto. CT scan of the chest demonstrated gastroesophageal junction lymphadenopathy, right hilar lymphadenopathy, numerous lung metastases and a prominent lesion in the left lower lung. Laboratory studies included both a low and high dexamethasone suppression test demonstrating a cortisol level 24 mcg/dL, metanephrines &lt; 0.2 nmol/L, low testosterone 2.1 ng/dL (free) and 54 ng/dL (total), and DHEA 7.1 ng/mlL. Aldosterone &lt;4.0 ng/dL and ACTH &lt; 5 pg/mL. Biopsy for the adrenal mas was consistent with cortical neoplasm. Surgery recommend against debulking due to wide-spread metastases. Oncology recommended chemotherapy; a regimen of mitotane, etoposide, doxorubicin, and cisplatin, with glucocorticoid replacement in 28-day cycles x 6 through venous port. Conclusion: Adrenocortical carcinoma is a rare, aggressive tumor that often secretes excess cortisol and/or androgens. In the case presented a large advanced stage ACC was nonfunctional. First-line therapy for ACC includes resection with debulking surgery, radiation therapy, and/or chemotherapy. 5-year survival rates range 62-82% for those with disease confined to the adrenal gland and 13% for tumors associated with distant metastases. Repeat CT scans for our patient demonstrated stable appearance after four cycles of chemotherapy, thus indicating this treatment regimen may be beneficial for such an aggressive disease.

scholarly journals Neural stemness unifies cell tumorigenicity and pluripotent differentiation potential

2021 ◽  
Author(s):  
Min Zhang ◽  
Yang Liu ◽  
Lihua Shi ◽  
Lei Fang ◽  
Liyang Xu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Ribosome Biogenesis ◽  
Regulatory Networks ◽  
Neural Induction ◽  
Neural Cells ◽  
Developmental Programs ◽  
Differentiation Potential ◽  
Gradual Loss ◽  
The Status ◽  
Original Cell

Tumorigenicity and pluripotent differentiation potential are kernel cell properties for tumorgenesis and embryogenesis. A growing number of studies have demonstrated that neural stemness is the source of the two cell properties, because neural stem cells and cancer cells share cell features and regulatory networks and neural stemness has an evolutionary advantage. However, it needs to validate whether neural stemness is a cell property that would unify tumorigenicity and pluripotent differentiation potential. SETDB1/Setdb1 is an epigenetic factor that is upregulated in cancer cells and promotes cancers, and correspondingly, is enriched in embryonic neural cells during vertebrate embryogenesis. We show that knockdown of SETDB1/Setdb1 led to neuronal differentiation in neural stem and cancer cells, concomitant with reduced tumorigenicity and pluripotent differentiation potential in these cells; whereas overexpression caused an opposite effect. On one hand, SETDB1 maintains a regulatory network comprised of proteins involved in developmental programs and basic cellular functional machineries, including epigenetic modifications (EZH2), ribosome biogenesis (RPS3), translation initiation (EIF4G), spliceosome assembly (SF3B1), etc., all of which play active roles in cancers. On the other, it represses transcription of genes promoting differentiation and cell cycle and growth arrest. Moreover, neural stemness, tumorigenicity and pluripotent differentiation potential were simultaneously enhanced during serial transplantation of cancer cells. Expression of proteins involved in developmental programs and basic cellular functional machineries, including SETDB1 and other proteins above, was gradually increased. In agreement with increased expression of spliceosome proteins, alternative splicing events also increased in tumor cells derived from later transplantations, suggesting that different machineries should work concertedly to match the status of high proliferation and pluripotent differentiation potential. The study presents the evidence that neural stemness unifies tumorigenicity and differentiation potential. Tumorigenesis represents a process of gradual loss of original cell identity and gain of neural stemness in somatic cells, which might be a distorted replay of neural induction during normal embryogenesis.

Do rare cancer cells have a tale to tell?

2007 ◽  
Author(s):  
Carmen Phillips
Keyword(s):  
Cancer Cells ◽  
Rare Cancer

scholarly journals Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gabriela Carrasco-Torres ◽  
Rafael Baltiérrez-Hoyos ◽  
Erik Andrade-Jorge ◽  
Saúl Villa-Treviño ◽  
José Guadalupe Trujillo-Ferrara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Maleic Anhydride ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Malignant Tumors ◽  
Combined Treatment ◽  
Current Data ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.

scholarly journals Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Odeya Marciano ◽  
Linoy Mehazri ◽  
Sally Shpungin ◽  
Alexander Varvak ◽  
Eldad Zacksenhaus ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Metastatic Cancer ◽  
Carcinoma Cells ◽  
Metabolic Adaptation ◽  
Hypoxic Stress ◽  
Lung Carcinoma Cells ◽  
Metabolic Role ◽  
Highly Sensitive ◽  
Anticancer Treatment

Aerobic glycolysis is an important metabolic adaptation of cancer cells. However, there is growing evidence that reprogrammed mitochondria also play an important metabolic role in metastatic dissemination. Two constituents of the reprogrammed mitochondria of cancer cells are the intracellular tyrosine kinase Fer and its cancer- and sperm-specific variant, FerT. Here, we show that Fer and FerT control mitochondrial susceptibility to therapeutic and hypoxic stress in metastatic colon (SW620) and non-small cell lung cancer (NSCLC-H1299) cells. Fer- and FerT-deficient SW620 and H1299 cells (SW∆Fer/FerT and H∆Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions. Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW∆Fer/FerT and H∆Fer/FerT cells compared to the parental SW620 and H1299 cells. Notably, selective knockout of the fer gene without affecting FerT expression reduced sensitivity to metformin and hypoxia seen in SW∆Fer/FerT cells. Thus, Fer and FerT modulate the mitochondrial susceptibility of metastatic cancer cells to hypoxia and metformin. Targeting Fer/FerT may therefore provide a novel anticancer treatment by efficient, selective, and more versatile disruption of mitochondrial function in malignant cells.

scholarly journals Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2064
Author(s):  
Piero Colombatto ◽  
Coskun Ozer Demirtas ◽  
Gabriele Ricco ◽  
Luigi Civitano ◽  
Piero Boraschi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progressive Disease ◽  
Kinase Inhibitors ◽  
Tumor Vasculature ◽  
Carcinoma Cells ◽  
Imaging Biomarkers ◽  
Additional Dose ◽  
Tissue Ischemia ◽  
Serological Biomarkers ◽  
Dose Dependent

In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (α-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C × day−1). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization.

scholarly journals Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain

2021 ◽  
Vol 30 ◽  
pp. 096368972097821
Author(s):  
Andrea Tenorio-Mina ◽  
Daniel Cortés ◽  
Joel Esquivel-Estudillo ◽  
Adolfo López-Ornelas ◽  
Alejandro Cabrera-Wrooman ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Ectopic Expression ◽  
Neural Induction ◽  
Human Keratinocytes ◽  
Differentiation Potential ◽  
Neuronal Proteins ◽  
Green Fluorescent

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.

Sign in / Sign up

Export Citation Format

Share Document