Journal of cancer stem cell research最新文献

{"title":"Proteolysis-targeting Chimeras Technology for Selective Protein Degradation","authors":"Yeqing Xia","doi":"10.54762/ccr2021.795-806","DOIUrl":"https://doi.org/10.54762/ccr2021.795-806","url":null,"abstract":"Proteolysis-targeting chimeras technology has emerged as a new therapeutic strategy that take advantage of endogenous ubiquitin-proteasome system (UPS) to selectively degrade oncoproteins. It has been developed from peptide-based PROTACs to small molecule-based ones, with capability to degrade a variety of target proteins with unprecedented advantages compared with traditional inhibitors. PROTACs have attracted the interest of both academia and industry and developed rapidly in the past decades. To date, there has been approximately 13 drugs already entered the clinic. However, as a new technology, it is facing many problems and challenges as well. This review will begin with introduction of common structure and rational design of PROTACs, with concentration on their significant features compared with traditional inhibitors. Then, different types of PROTACs will be discussed, followed by brief description of PRATACs that have reached the clinical stage.","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83287450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Observation on the Improvement of Quality of Life in Patients with Advanced Non-small Cell Lung Cancer by DC-CIK Maintenance Therapy Combined with Traditional Chinese Medicine Therapy","authors":"Jun Huang, Wei Zhang, Qi Zhou","doi":"10.54762/ccr2021.789-794","DOIUrl":"https://doi.org/10.54762/ccr2021.789-794","url":null,"abstract":"Objective: To explore and observe the effect of DC-CIK maintenance therapy combined with traditional Chinese medicine treatment on the improvement of quality of life in patients with advanced non-small cell lung cancer (NSCLC). Methods: The research period was from January 2017 to April 2018. 89 patients with advanced NSCLC who were diagnosed and treated in our hospital. They were divided into observation group 49 cases and control group 40 cases. Record the improvement of the quality of life. Results: After treatment, the short-term total effective rates of the observation group and the control group were 71.4% and 42.5% respectivel. The rate of the observation group was significantly higher than that of the control group (P<0.05). CD8+, CD3+ and CD4+ in the observation group and the control group after treatment were significantly different from those before treatment. And there was a statistically significant difference (P<0.05). Conclusion: DC-CIK maintenance therapy combined with traditional Chinese medicine treatment of advanced NSCLC patients can improve the quality of life, improve the body's immune ability, reduce the occurrence of adverse reactions, thereby improving the therapeutic effect.","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73625869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of Exosome in the Pathogenesis, Diagnosis and Treatment of Esophageal Squamous Cell Carcinoma","authors":"","doi":"10.54762/ccr2021.778-783","DOIUrl":"https://doi.org/10.54762/ccr2021.778-783","url":null,"abstract":"","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89350147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-203 inhibits cell proliferation, invasion, and migration of ovarian cancer through regulating RGS17","authors":"","doi":"10.54762/ccr2021.784-788","DOIUrl":"https://doi.org/10.54762/ccr2021.784-788","url":null,"abstract":"","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82074357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin enhances migration of human neuroblastoma cells: in vitro studies and potential therapeutic implications.","authors":"Agata Poniewierska-Baran,&nbsp;Justyna Rajewska-Majchrzak,&nbsp;Mariusz Z Ratajczak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The erythropoietin receptor (EpoR) is expressed by cells from the erythroid lineage; however, evidence has accumulated that it is also expressed by some other non-hematopoietic tissues including several solid tumor cells and proposed candidates for cancer stem cells. This is an important concern, because recombinant erythropoietin (EPO) is frequently employed in cancer patients as a drug to ameliorate anemia related to chemo/radiotherapy. In our studies, we employed three human neuroblastoma (NB) cell lines and found in all of them the expression of EpoR and EPO mRNA. The functionality of EpoR in RMS cell lines was evaluated by chemotaxis, adhesion, and direct cell proliferation assays. We noticed that all three human NB cell lines responded to EPO stimulation by enhanced chemotaxis and cell adhesion. However, at the same time we did not observe any significant effect of EPO on proliferation. Based on this EPO supplementation in NB patients employed because of radio/chemotherapy induced anemias may have an unwanted side effect on tumor metastasis.</p>","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978773/pdf/nihms920366.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36189696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Physiologic Microenvironments in Three-Dimensional Microtumors Maintains Brain Tumor Initiating Cells.","authors":"Ashley N Gilbert, Kiera Walker, Anh Nhat Tran, Nathaniel H Boyd, G Yancey Gillespie, Raj K Singh, Anita B Hjelmeland","doi":"10.14343/JCSCR.2017.5e1004","DOIUrl":"10.14343/JCSCR.2017.5e1004","url":null,"abstract":"<p><p>Development of effective novel anti-tumor treatments will require improved in vitro models that incorporate physiologic microenvironments and maintain intratumoral heterogeneity, including tumor initiating cells. Brain tumor initiating cells (BTIC) are a target for cancer therapy, because BTICs are highly tumorigenic and contribute to tumor angiogenesis, invasion, and therapeutic resistance. Current leading studies rely on BTIC isolation from patient-derived xenografts followed by propagation as neurospheres. As this process is expensive and time-consuming, we determined whether three-dimensional microtumors were an alternative in vitro method for modeling tumor growth via BITC maintenance and/or enrichment. Brain tumor cells were grown as neurospheres or as microtumors produced using the human-derived biomatrix HuBiogel™ and maintained with physiologically relevant microenvironments. BITC percentages were determined using cell surface marker expression, label retention, and neurosphere formation capacity. Our data demonstrate that expansion of brain tumor cells as hypoxic and nutrient-restricted microtumors significantly increased the percentage of both CD133+ and CFSE^high cells. We further demonstrate that BTIC-marker positive cells isolated from microtumors maintained neurosphere formation capacity in the in vitro limiting dilution assay and tumorigenic potential in vivo. These data demonstrate that microtumors can be a useful three-dimensional biological model for the study of BTIC maintenance and targeting.</p>","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653320/pdf/nihms911357.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35494890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitronectin in the ascites of human ovarian carcinoma acts as a potent chemoattractant for ovarian carcinoma: Implication for metastasis by cancer stem cells.","authors":"Gabriela Schneider,&nbsp;Malwina Suszynska,&nbsp;Sham Kakar,&nbsp;Mariusz Z Ratajczak","doi":"10.14343/JCSCR.2016.4e1005","DOIUrl":"https://doi.org/10.14343/JCSCR.2016.4e1005","url":null,"abstract":"<p><p>Vitronectin has been identified mainly as an adhesion protein that signals through uPAR and selected integrin receptors. In addition to its pro-adhesive properties, we identified recently vitronectin as a main chemoattractant present in diluted plasma/serum that directly stimulates migration of cancer cells. We also found that this pro-migratory activity of vitronectin can be quenched by fibrinogen. Based on this we hypothesized that this may explain preference of cancer cell to metastasize to fibrinogen-low microenvironments such as lymphatics or peritoneal cavity. Based on this, we decided to investigate a role of vitronectin in metastasis of ovarian cancer cells to peritoneal cavity. We tested migratory responsiveness of three human ovarian cancer cell lines to ascites isolated from ovarian cancer patients and characterize possible molecules involved in migration of ovarian cancer cells. The ascites samples were exposed to heat inactivation, proteinase K digested, dialyzed and charcoal stripped. We also performed cut-off filtration analysis and by employing ELISA assays to measure concentration of vitronectin in ascites fluid samples. Finally, we employed shRNA against uPAR and small molecular inhibitors of integrin receptors to assess their involvement in biological effects of vitronectin. From our studies, we found that the similarly to diluted plasma, vitronectin in absence of fibrinogen is a main chemotactic/chemokinetic protein present in ascites fluid. We also found that these pro-migratory properties of vitronectin can be quenched by addition of fibrinogen. Our studies also indicate that both uPAR and integrin receptors on ovarian cancer cells regulate migration of these cells to vitronectin gradient. In summary, we identified free soluble vitronectin as a potent direct chemoattractant for ovarian cancer cells and that its activity is suppressed after binding to fibrinogen. Since in ascites fluids vitronectin is present in free form because of a lack or low level of fibrinogen, this could explain preferences of ovarian cancer stem cells to metastasize within peritoneum. We propose that inhibitors which could sequester soluble vitronectin in similar fashion as fibrinogen, could be employed as a novel anti-metastatic drugs.</p>","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461934/pdf/nihms830144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35079400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer.","authors":"S. Kakar, Christopher A Worth, Zhenglong Wang, Kelsey Carter, M. Ratajczak, Pranesh Gunjal","doi":"10.14343/JCSCR.2016.4E1002","DOIUrl":"https://doi.org/10.14343/JCSCR.2016.4E1002","url":null,"abstract":"Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity. Resistance to chemotherapy and recurrence of cancer is primarily attributed to the presence of cancer stem cells (CSCs), a small population of cells present in cancer. Effect of DOXIL and withaferin A (WFA), both alone and in combination, was investigated on cell proliferation of ovarian cancer cell line A2780 and tumor growth in SCID mice bearing i.p. ovarian tumors. ALDH1 cells were isolated from A2780 using cell sorter, and effect of DOXIL and WFA both alone and in combination on tumorigenic function of ALDH1 was studied using spheroids formation assays in vitro. Western blots were performed to examine the expression of ALDH1 and Notch 1 genes. In our studies, we showed, for the first time, that DOXIL when combined with withaferin A (WFA) elicits synergistic effect on inhibition of cell proliferation of ovarian cancer cells and inhibits the expression of ALDH1 protein, a marker for ALDH1 positive cancer stem cells (CSCs), and Notch1, a signaling pathway gene required for self-renewal of CSCs. Inhibition of expression of both ALDH1 and Notch1 genes by WFA was found to be dose dependent, whereas DOXIL (200 nM) was found to be ineffective. SCID mice, bearing i.p. ovarian tumors, were treated with a small dose of DOXIL (2 mg/kg) in combination with a sub-optimal dose of WFA (2 mg/kg) which resulted in a highly significant (60% to 70%) reduction in tumor growth, and complete inhibition of metastasis compared to control. In contrast, WFA treatment showed a significant reduction in tumor growth but no change in metastasis compared to control. DOXIL showed non-significant reduction in tumor growth and no change in metastasis compared to control. Isolated ALDH1 positive CSCs treated with the combination of DOXIL and WFA resulted in a significant reduction in spheroids formation (tumorigenic function of CSCs) and expression of ALDH1 protein. WFA when used alone at a concentration of 1.5 μM was found to be highly effective in suppression of ALDH1 expression, whereas DOXIL at a concentration of 200 nM was found to be ineffective. DOXIL in combination with WFA elicits synergistic effects, targets cancer stem cells, and has potential to minimize induction of drug resistance and reoccurrence of cancer. Based on our studies, we conclude that the combination of DOXIL with WFA has the potential to be an effective therapy for ovarian cancer and may ameliorate DOXIL related side effects as well as recu","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67066095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An emerging question about putative cancer stem cells in established cell lines-are they true stem cells or a fluctuating cell phenotype?","authors":"Pranesh Gunjal, D. Pędziwiatr, A. A. Ismail, S. Kakar, M. Ratajczak","doi":"10.14343/JCSCR.2015.3E1004","DOIUrl":"https://doi.org/10.14343/JCSCR.2015.3E1004","url":null,"abstract":"It has been proposed that established cell lines contain populations of cancer stem cells (CSCs), which are responsible for expansion of these cell lines and their metastatic potential. To address this issue better, we employed a human ovarian cancer cell line, A2780, and sorted cells according to the postulated highly mestatatic cancer stem cell phenotype, CD24+CD44-, and the less-metastatic CD24-CD44+ and CD24-CD44- phenotypes. These cells were employed in chemotaxis assays in vitro to migrate in response to conditioned media harvested from bone marrow or liver cells damaged by irradiation and in in vivo assays to grow tumors after injection into immunodeficient mice. We also sorted single cells expressing all three phenotypes by FACS and expanded them to grow clones. We found that the CD24+CD44- cells are a highly migratory population compared with CD24-CD44+ and CD24-CD44- cells and were seeded in higher numbers in murine bone marrow and liver after intravenous injection. Most importantly, we observed that singly sorted cells efficiently expanded ex vivo into cell populations that represented all phenotypes of the parental cell line. Thus, our data indicate that cells expressing a certain set of markers, e.g., CD24, have at any given moment a higher potential to migrate and metastasize. However, cells that are CD24-negative, if expanded from a singly sorted cell, may give rise to cells containing all of the markers, including CD24. Based on this finding, we propose that the CSC phenotype in cell lines fluctuates with cell expansion.","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67065815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High expression of miR-9 in CD133⁺ glioblastoma cells in chemoresistance to temozolomide.","authors":"Jessian L Munoz,&nbsp;Vivian Rodriguez-Cruz,&nbsp;Pranela Rameshwar","doi":"10.14343/JCSCR.2015.3e1003","DOIUrl":"https://doi.org/10.14343/JCSCR.2015.3e1003","url":null,"abstract":"<p><p>Glioblastoma Multiforme (GBM), a uniformly lethal stage IV astrocytoma, is currently treated with a combination of surgical and radiation therapy as well as Temozolomide (TMZ) chemotherapy. Resistance to TMZ is rapidly acquired by GBM cells and overcoming this resistance has been an area of signi?cant research. GBM 'cancer stem cells' (CSC) also known as 'cancer initiating cells' are often positively selected by CD133 expression and TMZ resistance. In this project, we selected GBM CSC from two cell lines based on CD133 expression. CD133⁺ and CD133^- GBM cells showed comparable cell cycle status. The expression of genes within the Sonic Hedgehog Signaling pathway, PTCH1 (SHH receptor/basal signaling repressor) and Gli1 (effector transcription factor) were increased. The recent literature indicated a decreased in PTCH expression by miRNA and this was independent of SHH expression. We analyzed 5 potential PTCH-targeting miRNA and identi?ed an increase in miRNA-9-2. The CD133⁺ cells showed an increase in the Multiple Drug Resistance 1 gene (<i>MDR1</i>). Knockdown of Gli1 and MDR1 with siRNA enhanced TMZ induced cell death. Taken together, these studies show CD133⁺ GBM CSCs expressed greater levels of miR-9 and activation of the SHH/PTCH1/MDR1 axis. This axis has been shown to impart TMZ resistance. In the case of the CD133⁺ cells, the resistance is not acquires but seems to be inherent. Identi?cation of this pathway as well as the identi?cation of miR-9 may allow for the development of miRNA-targeted approach to Cancer Stem Cell therapy in GBM.</p>","PeriodicalId":90887,"journal":{"name":"Journal of cancer stem cell research","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917210/pdf/nihms-759000.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34613400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}