scholarly journals In silico ranking of phenolics for therapeutic effectiveness on cancer stem cells

2020 ◽  
Vol 21 (S21) ◽  
Author(s):  
Monalisa Mandal ◽  
Sanjeeb Kumar Sahoo ◽  
Priyadarsan Patra ◽  
Saurav Mallik ◽  
Zhongming Zhao
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Bipartite Graph ◽  
Treatment Options ◽  
Interaction Strength ◽  
Epigallocatechin Gallate ◽  
Weighted Bipartite Graph ◽  
Pharmacokinetic Properties ◽  
Phenolic Group ◽  
Ranking Technique

Abstract Background Cancer stem cells (CSCs) have features such as the ability to self-renew, differentiate into defined progenies and initiate the tumor growth. Treatments of cancer include drugs, chemotherapy and radiotherapy or a combination. However, treatment of cancer by various therapeutic strategies often fail. One possible reason is that the nature of CSCs, which has stem-like properties, make it more dynamic and complex and may cause the therapeutic resistance. Another limitation is the side effects associated with the treatment of chemotherapy or radiotherapy. To explore better or alternative treatment options the current study aims to investigate the natural drug-like molecules that can be used as CSC-targeted therapy. Among various natural products, anticancer potential of phenolics is well established. We collected the 21 phytochemicals from phenolic group and their interacting CSC genes from the publicly available databases. Then a bipartite graph is constructed from the collected CSC genes along with their interacting phytochemicals from phenolic group as other. The bipartite graph is then transformed into weighted bipartite graph by considering the interaction strength between the phenolics and the CSC genes. The CSC genes are also weighted by two scores, namely, DSI (Disease Specificity Index) and DPI (Disease Pleiotropy Index). For each gene, its DSI score reflects the specific relationship with the disease and DPI score reflects the association with multiple diseases. Finally, a ranking technique is developed based on PageRank (PR) algorithm for ranking the phenolics. Results We collected 21 phytochemicals from phenolic group and 1118 CSC genes. The top ranked phenolics were evaluated by their molecular and pharmacokinetics properties and disease association networks. We selected top five ranked phenolics (Resveratrol, Curcumin, Quercetin, Epigallocatechin Gallate, and Genistein) for further examination of their oral bioavailability through molecular properties, drug likeness through pharmacokinetic properties, and associated network with CSC genes. Conclusion Our PR ranking based approach is useful to rank the phenolics that are associated with CSC genes. Our results suggested some phenolics are potential molecules for CSC-related cancer treatment.

scholarly journals Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate

2017 ◽  
Vol 143 (12) ◽  
pp. 2401-2412 ◽  
Author(s):  
Hirota Fujiki ◽  
Eisaburo Sueoka ◽  
Anchalee Rawangkan ◽  
Masami Suganuma
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Prevention ◽  
Human Cancer ◽  
Epigallocatechin Gallate

scholarly journals Targeting the Epithelial-to-Mesenchymal Transition in Cancer Stem Cells for a Better Clinical Outcome of Glioma

2020 ◽  
Vol 19 ◽  
pp. 153303382094805
Author(s):  
Yu-bao Lu ◽  
Tian-Jiao Sun ◽  
Yu-tong Chen ◽  
Zong-Yan Cai ◽  
Jia-Yu Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Tumor Development ◽  
Mesenchymal Transition ◽  
Important Target ◽  
The Central Nervous System

Glioma is one of the most common malignant tumors of the central nervous system with a poor prognosis at present due to lack of effective treatment options. Its initiation, migration, and multipotency are affected by cancer stem cell’s transition. Previous studies imply that changes in the cancer stem cells can affect the malignant differentiation of the tumor. We found that the epithelial-to-mesenchymal transition (EMT)-related regulatory pathway is an important target for tumor therapy. In this review, we discuss the transition factor of EMT and 3 specific pathways that affect the EMT of cancer stem cells during tumor development. We conclude that targeting the EMT process of cancer stem cells can be a feasible approach in the treatment of glioma.

scholarly journals Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA

2021 ◽  
Vol 22 (16) ◽  
pp. 8901
Author(s):  
Kaya E. Witte ◽  
Jesco Pfitzenmaier ◽  
Jonathan Storm ◽  
Melanie Lütkemeyer ◽  
Clara Wimmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Treatment Options ◽  
Specific Treatment ◽  
Human Leukocyte ◽  
Patient Specific ◽  
Stem Cell Markers ◽  
Prostate Cancer Stem Cells ◽  
Beta 2 Microglobulin

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.

scholarly journals Cancer Stem Cells-Role in Oral Squamous Carcinoma - A Review of Literature

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 153-158
Author(s):  
Deepthi Sogasu ◽  
Devaraj Ezhilarasan ◽  
Smiline Girija AS
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumour Size ◽  
Treatment Options ◽  
Cell Formation ◽  
Squamous Carcinoma ◽  
Treatment Resistance ◽  
Review Of Literature ◽  
Oral Squamous Carcinoma

The cancer stem cells (CSC) are responsible for the growth of cancerous tumours. The renewal of cancer stem cells is considered synonymous with that of normal cells. The cancer cells are considered a progeny of specific and designated stem cells. The identification of these cancer stem cells has proven to be more difficult than anticipated due to the specific niches they are present in, within the tumour. Oral squamous carcinoma is the Sixth most common cancer constituting up to 2–4% of all malignancies worldwide and with poor prognosis. Tumour size and extent of lymph node metastasis are the most important predictors. The CSC works on the mechanism of bulk tumour cell formation and treatment resistance. But there are increased studies under this topic as it has been found that specifically targeting these cells can curb cancer. This review compiles information about the role of CSC in oral squamous cell carcinomas, the applications of CSC, and their use in the development of novel treatment options for oral cancer.

scholarly journals Targeting Ca2+ Signaling in the Initiation, Promotion and Progression of Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2755
Author(s):  
Eunus S. Ali ◽  
Grigori Y. Rychkov ◽  
Greg J. Barritt
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Trp Channels ◽  
Treatment Options ◽  
Laboratory Research ◽  
Future Application ◽  
Alcoholic Fatty Liver ◽  
Liver Cancer Stem Cells

Hepatocellular carcinoma (HCC) is a considerable health burden worldwide and a major contributor to cancer-related deaths. HCC is often not noticed until at an advanced stage where treatment options are limited and current systemic drugs can usually only prolong survival for a short time. Understanding the biology and pathology of HCC is a challenge, due to the cellular and anatomic complexities of the liver. While not yet fully understood, liver cancer stem cells play a central role in the initiation and progression of HCC and in resistance to drugs. There are approximately twenty Ca2+-signaling proteins identified as potential targets for therapeutic treatment at different stages of HCC. These potential targets include inhibition of the self-renewal properties of liver cancer stem cells; HCC initiation and promotion by hepatitis B and C and non-alcoholic fatty liver disease (principally involving reduction of reactive oxygen species); and cell proliferation, tumor growth, migration and metastasis. A few of these Ca2+-signaling pathways have been identified as targets for natural products previously known to reduce HCC. Promising Ca2+-signaling targets include voltage-operated Ca2+ channel proteins (liver cancer stem cells), inositol trisphosphate receptors, store-operated Ca2+ entry, TRP channels, sarco/endoplasmic reticulum (Ca2++Mg2+) ATP-ase and Ca2+/calmodulin-dependent protein kinases. However, none of these Ca2+-signaling targets has been seriously studied any further than laboratory research experiments. The future application of more systematic studies, including genomics, gene expression (RNA-seq), and improved knowledge of the fundamental biology and pathology of HCC will likely reveal new Ca2+-signaling protein targets and consolidate priorities for those already identified.

Feasibility of Targeting Glioblastoma Stem Cells: From Concept to Clinical Trials

2020 ◽  
Vol 19 (32) ◽  
pp. 2974-2984 ◽  
Author(s):  
Vadim V. Tarasov ◽  
Andrey A. Svistunov ◽  
Vladimir N. Chubarev ◽  
Tamara A. Zatsepilova ◽  
Nina G. Preferanskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Cancer Stem Cells ◽  
Treatment Options ◽  
Current Treatment ◽  
Clinical Settings ◽  
Glioblastoma Stem Cells ◽  
Pubmed Search ◽  
Number Of Treatment ◽  
Target Cancer

Objective: Glioblastoma is a highly aggressive and invasive brain and Central Nervous System (CNS) tumor. Current treatment options do not prolong overall survival significantly because the disease is highly prone to relapse. Therefore, research to find new therapies is of paramount importance. It has been discovered that glioblastomas contain a population of cells with stem-like properties and that these cells are may be responsible for tumor recurrence. Methods: A review of relevant papers and clinical trials in the field was conducted. A PubMed search with related keywords was used to gather the data. For example, “glioblastoma stem cells AND WNT signaling” is an example used to find information on clinical trials using the database ClinicalTrials.gov. Results: Cancer stem cell research has several fundamental issues and uncertainties that should be taken into consideration. Theoretically, a number of treatment options that target glioblastoma stem cells are available for patients. However, only a few of them have obtained promising results in clinical trials. Several strategies are still under investigation. Conclusion: The majority of treatments to target cancer stem cells have failed during clinical trials. Taking into account a number of biases in the field and the number of unsuccessful investigations, the application of the cancer stem cells concept is questionable in clinical settings, at least with respect to glioblastoma.

scholarly journals The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1092
Author(s):  
Céline Hervieu ◽  
Niki Christou ◽  
Serge Battu ◽  
Muriel Mathonnet
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Cancer Stem Cells ◽  
Treatment Options ◽  
Therapy Resistance ◽  
Attractive Potential ◽  
Unique Challenge ◽  
Novel Therapeutic Strategies

The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient’s overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity.

ROLE OF CANCER STEM CELLS IN OVARIAN CARCINOGENESIS

2020 ◽  
pp. 82-103
Author(s):  
S.O. Gening ◽  
I.I. Antoneeva
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Treatment Options ◽  
Tumor Stroma ◽  
Biological Properties ◽  
Google Scholar ◽  
Human Stem Cells ◽  
Secondary Resistance ◽  
Keywords Ovarian Cancer

Ovarian cancer (OC) is an aggressive malignant tumor (MT) with a relapsing course and a low 5-year survival rate. Most cases are diagnosed at advanced stages, while treatment options for OC are limited. Thus, the development of primary or secondary resistance to standard chemotherapy is often fatal for patients. MT heterogeneity contributes to the survival of the most adapted cells during the selection; such cells need high tumorigenicity in the site of a disease for further expansion of the surviving clone and fixation of a stable phenotype in the focus. Cancer stem cells (CSCs) combine these characteristics and are at the top of the hierarchical tumor structure. Their biological properties, such as the ability to self-renewal, and multilinear differentiation, are similar to those of normal human stem cells. Phenotypic plasticity and interaction with other parenchyma components, tumor stroma, and extra-tumor elements allow CSCs to withstand unfavorable conditions, such as chemotherapy, immunological surveillance, physical damaging factors and anoikis in the blood and lymphatic bed, and unusual microenvironment of targeted metastasis organs in the case of distant metastasis. More and more research articles are devoted to finding ways to use CSCs as a predictive and prognostic biomarker and as a target for therapy. However, unambiguous identification of CSCs, their counting, and specific elimination are a difficult problem. Currently, science is at the stage of accumulating data on this topic. The review summarizes current advances in understanding CSC biology and their impact on OC clinical progression. The literature search was carried out in PubMed, Google Scholar, and eLibrary databases. Keywords: ovarian cancer, cancer stem cells, chemotherapy, carcinogenesis, drug resistance. Рак яичников (РЯ) – агрессивная злокачественная опухоль (ЗО) с рецидивирующим течением и низкой 5-летней выживаемостью пациенток. Большинство случаев диагностируется на распространенных стадиях, а терапевтические опции при РЯ ограничены, поэтому развитие первичной или вторичной резистентности к стандартной химиотерапии часто является фатальным для больной. Гетерогенность ЗО приводит к тому, что в ходе селекции выживают наиболее адаптированные клетки; для дальнейшей экспансии выжившего клона и закрепления устойчивого фенотипа в очаге им необходима высокая туморогенность. Стволовые опухолевые клетки (СОК) сочетают в себе эти характеристики и стоят на вершине иерархической структуры опухоли. Их биологические свойства, такие как способность к самообновлению, мультилинейная дифференцировка, схожи со свойствами нормальных стволовых клеток человека. Пластичность фенотипа и взаимодействие с иными составляющими паренхимы, стромы опухоли, а также внеопухолевыми элементами позволяют СОК противостоять неблагоприятным условиям: воздействию химиопрепаратов, иммунологическому надзору, физическим повреждающим факторам и аноикису в кровеносном и лимфатическом русле, непривычному микроокружению таргетных органов при отдаленном метастазировании. Все больше работ посвящается поиску путей использования СОК как предиктивного и прогностического биомаркера и как мишени для терапии, однако их однозначная идентификация, подсчет и специфическая элиминация представляют сложную проблему. В настоящее время наука находится на этапе накопления данных по этой тематике. В обзоре суммированы современные достижения в понимании биологии СОК и их влияния на клиническое течение РЯ. Поиск литературы осуществлялся по базам данных PubMed, Google Scholar, eLibrary. Ключевые слова: рак яичников, стволовые опухолевые клетки, химиотерапия, канцерогенез, лекарственная устойчивость.

Sign in / Sign up

Export Citation Format

Share Document