scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

scholarly journals Role of Cancer Stem Cells in Spine Tumors

Neurosurgery ◽  
2012 ◽  
Vol 71 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Wesley Hsu ◽  
Ahmed Mohyeldin ◽  
Sagar R. Shah ◽  
Ziya L. Gokaslan ◽  
Alfredo Quinones-Hinojosa
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Surgical Intervention ◽  
Spinal Column ◽  
Primary Tumors ◽  
Tumorigenic Potential ◽  
Active Investigation

Abstract The management of spinal column tumors continues to be a challenge for clinicians. The mechanisms of tumor recurrence after surgical intervention as well as resistance to radiation and chemotherapy continue to be elucidated. Furthermore, the pathophysiology of metastatic spread remains an area of active investigation. There is a growing body of evidence pointing to the existence of a subset of tumor cells with high tumorigenic potential in many spine cancers that exhibit characteristics similar to those of stem cells. The ability to self-renew and differentiate into multiple lineages is the hallmark of stem cells, and tumor cells that exhibit these characteristics have been described as cancer stem cells (CSCs). The mechanisms that allow nonmalignant stem cells to promote normal developmental programming by way of enhanced proliferation, promotion of angiogenesis, and increased motility may be used by CSCs to fuel carcinogenesis. The purpose of this review is to discuss what is known about the role of CSCs in tumors of the osseous spine. First, this article reviews the fundamental concepts critical to understanding the role of CSCs with respect to chemoresistance, radioresistance, and metastatic disease. This discussion is followed by a review of what is known about the role of CSCs in the most common primary tumors of the osseous spine.

Detection of circulating cancer stem cells (cCSCs) as a predictive biomarker for breast cancer relapse or metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14559-e14559
Author(s):  
Monika Pizon ◽  
Ulrich A. Pachmann ◽  
Katharina Pachmann ◽  
Dorothea Schott
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Surface Marker ◽  
Breast Cancer Patients ◽  
Stage Of Disease ◽  
Surface Marker Expression ◽  
Sphere Formation

e14559 Background: Breast cancer is one of the most common types of cancer in women worldwide. It has been demonstrated that even localized tumors without clinically apparent metastases give rise to circulating epithelial tumor cells (CETCs). Recent studies have provided strong support for the cCSC hypothesis, which suggests that a more aggressive subpopulation of circulating tumor cells is the source of metastatic spread from the primary tumor. Measuring CETCs in blood of patients has emerged as a non-invasive diagnostic procedure for screening patients who may be at high risk for developing metastatic cancers. However, accurate detection of CETCs may provide erroneous results, since CETCs undergoing EMT during metastasis are down-regulated for the expression of epithelial cell markers. Methods: 26 breast cancer patients were included into the study. The determination of CETCs and cCSC was performed using maintrac method and tumorsphere forming assay, respectively. Cell viability, surface marker expression and ALDH 1 activity of the cells in the spheres were evaluated by fluorescence scanning microscope. Results: Sphere formation was observed in 80 % of patients. We found that the number of tumorspheres depended on stage of disease. The number of tumorspheres increased significantly with tumor progression, especially with the presence of metastases. Tumorsphere formation was observed in all metastatic patients (median of 30 tumorspheres/100µl of blood), although only 27% of them had detectable CETCs. Analysis of surface marker expression profile showed that the cells in the spheres had typical phenotype of cancer stem cells. Sphere formation was not observed in healthy subjects (n = 20). Conclusions: There is a high correlation between the numbers of tumorspheres cultured from peripheral blood with clinical stage of disease. Identifying cCSC in blood sample can help clinicians to monitor breast cancer patients and to detect metastasis in early stages.

Immunological targeting of CD133 in recurrent glioblastoma: A multi-center phase I translational and clinical study of autologous CD133 dendritic cell immunotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2059-2059 ◽  
Author(s):  
Jeremy David Rudnick ◽  
Karen L. Fink ◽  
Joseph C. Landolfi ◽  
James Markert ◽  
David Eric Piccioni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Overall Survival ◽  
Dendritic Cell ◽  
Cancer Stem Cells ◽  
Phase I ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Target Antigen ◽  
Induction Phase

2059 Background: A hallmark of glioblastoma is the high incidence of tumor recurrence, thought to be triggered by cancer stem cells. These tumorigenic cells are resistant to irradiation and chemotherapeutic agents. The target antigen, CD-133, was chosen because it has been reported as a cancer stem cell antigen overexpressed in glioblastoma tumors and associated with shorter survival. Recent clinical trials suggest that the mean overall survival for these patients is roughly 5-9 months, emphasizing the important unmet medical need in this disease requiring additional strategic approaches. Dendritic cell immunotherapies such as ICT-121 could provide benefit to patients by educating their immune systems to induce the formation of cytotoxic T cells that attack tumor cells bearing the target antigen. In addition to immediate attack on tumor cells present at dosing, a long-term memory response effective against tumor recurrence might be induced. Immunotherapy, such as ICT-121, that targets cancer stem cells could be an important treatment for this disease. Methods: This Phase I multi-center trial of ICT-121 targeting CD133 was designed to assess safety and tolerability (primary endpoint) and to monitor overall survival and progression-free survival (secondary endpoints). ICT-121 is comprised of autologous dendritic cells that are loaded with two HLA-A2 restricted epitopes of the CD133 antigen. CD133 is overexpressed on glioblastoma cancer stem cells. The HLA-A2 patients that had undergone resection for recurrence of glioblastoma were treated with ICT-121 once a week for 4 weeks during the induction phase and then once every 2 months during the maintenance phase until disease progression, death, ICT-121 depletion or discontinuation. Results: A total of 20 patients were treated and eight of these patients are still alive. Immune response data with cytokine mRNA expression demonstrated a response to the CD133 epitopes. A total of 20 patients were treated and eight of these patients are still alive. Conclusions: The results from this Phase I trial suggest that ICT-121 is both safe and well-tolerated with an immune response seen in a subset of patients. Clinical trial information: NCT02049489.

Salinomycin reduces the viability of circulating epithelial tumor cells (CETCs) and tumorspheres cultured from circulating cancer stem cells (cCSC) and may potentially prevent progression in patients with solid cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23143-e23143
Author(s):  
Monika Pizon ◽  
Dorothea Schott ◽  
Katharina Pachmann ◽  
Ulrich Pachamnn ◽  
Norbert Szalus
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cytotoxic Effect ◽  
Solid Cancer ◽  
Dependent Manner ◽  
Epithelial Tumor ◽  
Short Time

e23143 Background: Recently the hypothesis has been proposed that a more aggressive subpopulation of circulating tumor cells, circulating cancer stem cells are the source of metastatic spread from the primary tumor. These cells are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. The antibiotic Salinomycin has been shown to reduce the expression of markers for stemness and spheroid-forming ability. In this study, we evaluated the cytotoxic effect of salinomycin on CETCs and tumorspheres cultured from cCSC. Methods: 20 patients with solid tumors in different stages of disease were included. The determination of CETCs and cCSC was performed using maintrac method and tumorsphere forming assay, respectively. To evaluate the cytotoxic effect of salinomycin on CETCs and spheroids they were exposed to different concentrations of salinomycin in short time culture for different periods of time. Results: 80% of patients had detectable CETCs but sphere formation was observed in 95% of solid cancer patients. Growth of spheroids was detected also in patients without CETCs. The number of tumorspheres increased significantly with tumor progression. Treatment with salinomycin showed an 80% reduction in spheroid formation compared with control. Salinomycin reduced the viability of spheroids in a dose–dependent manner. Salinomycin had stronger cytotoxic effect on CETCs in non-metastatic as compared to metastatic patients (median of dead CETCs 85% vs. 34%, p < 0.001). Patients without chemotherapy responded better to salinomycin treatment than patients after several lines of chemotherapy (median of dead CETCs 87%vs.35%, p < 0.001) Conclusions: Using a method for cultivation of tumorspheres from blood of cancer patients and an effective in vitro platform for screening anti-cancer stem cells drugs was developed. Thus it could be shown that salinomycin targets not only more differentiated circulating cancer cells but also cancer stem cells from peripheral blood. It may evolve as a novel and promising therapeutic strategy for future cancer treatment

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 PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2168
Author(s):  
Balawant Kumar ◽  
Rizwan Ahmad ◽  
Swagat Sharma ◽  
Saiprasad Gowrikumar ◽  
Mark Primeaux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Therapy Resistance ◽  
Fluorescent Reporter ◽  
Combination Treatments ◽  
Gsk 3Β ◽  
Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

Targeting pancreatic cancer stem cells for cancer therapy

2012 ◽  
Vol 1826 (2) ◽  
pp. 385-399 ◽  
Author(s):  
Jun Xia ◽  
Changjie Chen ◽  
Zhiwen Chen ◽  
Lucio Miele ◽  
Fazlul H. Sarkar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Pancreatic Cancer Stem Cells

scholarly journals Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1385
Author(s):  
Hyeon-Yeol Cho ◽  
Jin-Ha Choi ◽  
Joungpyo Lim ◽  
Sang-Nam Lee ◽  
Jeong-Woo Choi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Cancer Prognosis ◽  
Optical Biosensors ◽  
Diagnosis And Prognosis ◽  
Noise Factors ◽  
Prediction Of Relapse

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

Sign in / Sign up

Export Citation Format

Share Document