scholarly journals Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Cheng-Chia Yu ◽  
Wen-Liang Lo ◽  
Yi-Wei Chen ◽  
Pin-I Huang ◽  
Han-Shui Hsu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Volume ◽  
Distant Metastases ◽  
Cancer Stemness ◽  
Snail Expression ◽  
Metastatic Lesions ◽  
Squamous Cancer ◽  
Regulation Mechanisms ◽  
Putative Marker ◽  
Hnscc Patient

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+cells remain unclear. Initially, HNSCC-ALDH1+cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression propertyALDH1−cells to that ofALDH1+cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1−cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+cells.

Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer

2009 ◽  
Vol 385 (3) ◽  
pp. 307-313 ◽  
Author(s):  
Yu-Chih Chen ◽  
Yi-Wei Chen ◽  
Han-Shui Hsu ◽  
Ling-Ming Tseng ◽  
Pin-I Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Head And Neck ◽  
Aldehyde Dehydrogenase ◽  
Aldehyde Dehydrogenase 1 ◽  
Squamous Cancer ◽  
Putative Marker

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany

2021 ◽  
Vol 9 (2) ◽  
pp. e001701
Author(s):  
Julia Maria Ressler ◽  
Matthias Karasek ◽  
Lukas Koch ◽  
Rita Silmbrod ◽  
Joanna Mangana ◽  
...  
Keyword(s):  
Chart Review ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Real Life ◽  
Retrospective Chart Review ◽  
Distant Metastases ◽  
Complete Response ◽  
Talimogene Laherparepvec ◽  
Metastatic Lesions ◽  
Melanoma Patients

BackgroundTalimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.ObjectivesThe aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.MethodsBased on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36–95 years) treated with T-VEC during the period from May 2016 to January 2020.Results88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1–65), an average of 11 doses (range: 1–36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).ConclusionThis real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs.

scholarly journals YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Hong-Chen Yan ◽  
Yu Sun ◽  
Ming-Yu Zhang ◽  
Shu-Er Zhang ◽  
Jia-Dong Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Self Renewal ◽  
Human Ascs ◽  
Regulation Mechanisms ◽  
Interfering Rna ◽  
Pluripotency Genes

Abstract Background Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of ASCs is a hot topic. Porcine models have close similarities to humans and porcine SDSCs (pSDSCs) offer an ideal in vitro model to investigate human ASCs. To date, studies concerning the role of yes-associated protein (YAP) in ASCs are limited, and the mechanism of its influence on self-renewal and differentiation of ASCs remain unclear. In this paper, we explore the link between the transcriptional regulator YAP and the fate of pSDSCs. Results We found that YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Sox2, Oct4. The overexpression of YAP prevented the differentiation of pSDSCs and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939 an inhibitor of Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Conclusions our results suggested that, YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs.

scholarly journals A Review of the Literature on Extrarenal Retroperitoneal Angiomyolipoma

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Anthony Kodzo-Grey Venyo
Keyword(s):  
Radical Nephrectomy ◽  
De Novo ◽  
Treatment Options ◽  
Distant Metastases ◽  
Surgical Excision ◽  
Radical Resection ◽  
Malignant Tumours ◽  
Selective Embolization ◽  
Metastatic Lesions ◽  
Benign Tumours

Background. Extrarenal retroperitoneal angiomyolipomas are rare.Aim. To review the literature.Results. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour.Conclusions. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions.

scholarly journals Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1058 ◽  
Author(s):  
Gener ◽  
Rafael ◽  
Seras-Franzoso ◽  
Perez ◽  
Pindado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Distant Metastases ◽  
Metastatic Potential ◽  
Phenotypic Change ◽  
Primary Tumors ◽  
Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

scholarly journals LSD1/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1821 ◽  
Author(s):  
Panagiotis Karakaidos ◽  
John Verigos ◽  
Angeliki Magklara
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cellular Reprogramming ◽  
Future Perspectives ◽  
Cancer Stemness ◽  
Neuronal Stem Cells ◽  
Lysine Specific Demethylase ◽  
Promising Therapeutic Target ◽  
Exciting Area ◽  
Established Role

A new exciting area in cancer research is the study of cancer stem cells (CSCs) and the translational implications for putative epigenetic therapies targeted against them. Accumulating evidence of the effects of epigenetic modulating agents has revealed their dramatic consequences on cellular reprogramming and, particularly, reversing cancer stemness characteristics, such as self-renewal and chemoresistance. Lysine specific demethylase 1 (LSD1/KDM1A) plays a well-established role in the normal hematopoietic and neuronal stem cells. Overexpression of LSD1 has been documented in a variety of cancers, where the enzyme is, usually, associated with the more aggressive types of the disease. Interestingly, recent studies have implicated LSD1 in the regulation of the pool of CSCs in different leukemias and solid tumors. However, the precise mechanisms that LSD1 uses to mediate its effects on cancer stemness are largely unknown. Herein, we review the literature on LSD1’s role in normal and cancer stem cells, highlighting the analogies of its mode of action in the two biological settings. Given its potential as a pharmacological target, we, also, discuss current advances in the design of novel therapeutic regimes in cancer that incorporate LSD1 inhibitors, as well as their future perspectives.

scholarly journals MicroRNAs as Theranostics Targets in Oral Carcinoma Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 340 ◽  
Author(s):  
Pei-Ling Hsieh ◽  
Yi-Wen Liao ◽  
Martin Pichler ◽  
Cheng-Chia Yu
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cancer Stemness ◽  
Aberrant Expression ◽  
The Past ◽  
Key Players ◽  
Non Coding Rnas ◽  
Theranostic Applications ◽  
Significant Attention

Oral cancer belongs to head and neck squamous cell carcinoma and has been recognized as one of the most prevalent malignancies worldwide. Recent studies have suggested that cancer stem cells (CSCs) may participate in tumor initiation, metastasis and even recurrence, so the regulation of CSCs has drawn significant attention over the past decade. Among various molecules that are associated with CSCs, non-coding RNAs (ncRNAs) have been indicated as key players in the acquisition and maintenance of cancer stemness. In addition, accumulating studies have shown that the aberrant expression of these ncRNAs may serve as surrogate diagnostic markers or even therapeutic targets for cancer treatment. The current study reviews the previous work by us and others to summarize how these ncRNAs affect oral cancer stemness and their potential theranostic applications. A better understanding of the implication of these ncRNAs in oral tumorigenesis will facilitate the translation of basic ncRNA research into clinical application in the future.

Tumor Volume is a Predictor of Distant Metastases and Overall Survival in Sinonasal Mucosal Melanoma

2020 ◽  
Vol 106 (5) ◽  
pp. 1190-1191
Author(s):  
S. Flukes ◽  
S. Lohia ◽  
C.A. Barker ◽  
J. Cracchiolo ◽  
I. Ganly ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Volume ◽  
Distant Metastases ◽  
Mucosal Melanoma
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