bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3314: Side population in renal cell carcinoma cell line is enriched with drug resistant, but not tumor initiating cells
Authors: Ong Choon Kiat , Wong Bernice Hui Min , Wong Jacey Jing Chii , Huang Da Chuan , Ooi Aik Seng , Qian Miles Chao Nan , Teh Bin Tean 
Published: February 2011

Abstract
Several lines of evidences suggested the presence of tumor initiating cells in renal cell carcinoma (RCC) and side population (SP) may be enriched with these “cancer stem cells (CSC)”. Herein we demonstrated the presence of Side population in 10 RCC cell lines ranging from 0.19 - 36.1%. Lineage tracing experiments showed that the SP can be enriched through sequential sorting and can differentiate into non-SP (NSP) which constitutes the bulk of the cells. The NSP can also formed back the original population of the SP in CRL1611 cells. Interestingly, the presence of NSP seem to prevent the SP from differentiating into NSP. The SP cells have about 15% higher proliferation rate and 50% greater colony forming efficiency which are reported characteristics of CSC. SP expresses higher level of cMyc, but lower level of CD105 as compared to the NSP. On the contrary, there is no difference in tumorigenic potential between SP and NSP using both correlation and in vivo studies. However, we verified that SP are 10% more resistance to mTOR inhibitor, RAD001 which coincide with higher expression of drug resistance membrane transporters ABCB1 and ABCG2 in SP cells. Treatment with RAD001 increases the amount of SP concomitantly up regulate ABCB1 and ABCC1 significantly. Taken together, Hoechst dye exclusion did not define tumor initiating cells, but is a valuable technique for identifying drug resistance cells in RCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3314.
Abstract 3315: TAC-101 induces the differentiation of cancer stem-like cells
Authors: Honda Shizu , Yamamoto Yasuji , Masuko Norio , Yokoi Hiromi , Ito Kenjiro , Fujita Ryoto , Matsuo Ken-ichi 
Published: February 2011

Abstract
TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), is an orally bioavailable synthetic retinoid, binding to nuclear retinoic acid receptor (RAR), activates selectively RAR alpha transcriptional. And TAC-101 has demonstrated anti-tumor activity and proplongation of survival in primary and metastatic liver cancer pre-clinical models.
In Phase I study, the lymph nodes of a non-small cell lung cancer patient with nodal metastasis returned to normal size, constituting a complete radiologic response. In a Phase I/II trial of TAC-101 in patients with advanced hepatocellular carcinoma, TAC-101 showed significant disease stabilization, 2 PRs after discontinuing TAC-101 treatment, and prolonged median survival, suggesting that TAC-101 provides meaningful patient'ss benefit.
Recently, many researchers have reported correlation between cancer stem-like cells and tumor malignancy, such as therapy-resistance. In addition, retinoids were reported to reduce the number of cells with the cancer stem cell marker.
So, we hypothesize that TAC-101 induces the differentiation of cancer stem-like cells, and contributes life span prolongation of patients of solid tumor.
We cultured A549 cancer cells in mediummedium containing 0.1 and 1 μM of TAC-101 for 8 weeks and analyzed the expression of several stem cell markers using flow cytomoetry technique. Detection method of side population was validated by the result that fumitremorgin C, inhibitor of ABCG2, could eliminate the side population.
We found that TAC-101 reduced side-population, CD326 (EpCAM) positive population and standard deviation of side scatter.
From these results, it is estimated that treatment of TAC-101 for a certain period of time will be enough to induce of differentiation and to reduce cancer stem-like cells, may result in the tumor shrinkage and prolongation of patient's survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3315.
Abstract 332: Analysis of HER gene family status in hepatocellular carcinoma by FISH
Authors: Chen Hui Wen , Chang Pi Chuan , Hsieh Sen Yung , Weng Wen Hui 
Published: February 2011

Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The incidence rate is much higher in developing countries than in industrialized countries. More than 75% of HCC cases occur in the Far East and Southeast Asia. Gene HER1 was known commonly overexpressed in many cancers including HCC. Overexpression of HER1 would lead to cell proliferation, migration, metastasis, antiapoptosis and angiogenesis. Therefore, HER1 has been widely considered as a predict biomarker in clinical purpose. For other epidermal growth factor receptor (EGFR; HER) family members, for example HER2, HER3, and HER4, except the HER1 and HER2, HER3, HER4 are seldom to be studied in HCC so far. To our knowledge, the role of HER3 play a distinct behavior in the EGFR family, which required heterodimerization with other HER family members, then follow to trigger the signaling transduction and, therefore, result in tumor cell proliferation, migration, invasion, anti-apoptosis, and increase angiogenesis. The high level expression of HER3 has been observed in breast, ovarian, and lung cancer etc. Hence, HER3 protein expression in HCC using immunohistochemistry was also showed significantly related to cell proliferation activity, tumor size, intrahepatic metastasis, portal invasion and carcinoma differentiation. Accordingly, we hypothesized that not only HER1 but also HER3 may play an important role in HCC, and the structure of gene and copy number changes may need further investigated.
We study the gene expression level of HER1 and HER3 in six HCC cell lines and twenty paraffin tissue samples using fluorescence in situ hybridization (FISH). Their expression level was also correlated with gene structures and/or gene copy number alterations.
Our result showed that the gene expression of HER1 consistent the previous reports. Most notably, the gene HER3 presented either the different level of copy number changes or gene structure alterations in all six cell lines. For, most of the clinical samples only gene structure aberrations could be observed. In addition, both gene HER1 and HER3 were highly expressed in Tong cell line when compared to other HCC cell lines.
The FISH results showed the alteration of genes structure and increased copy number of gene HER1 and HER3 in all cell lines. While the study on the clinical HCC samples revealed that the gene structural aberrations were more common than gene copy number alterations. However, further evidence from larger clinical samples is needed to clarify our current findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 332.
Abstract 3327: G-quadruplex-stabilizer, Telomestatin, preferentially induces apoptosis of brain tumor stem cells with less effect on survival of normal stem cells
Authors: Miyazaki Takeshi , Shin-ya Kazuo , Nakano Ichiro 
Published: February 2011

Abstract
Introduction: Recent studies have demonstrated the phenotypic and genetic similarities between brain tumor stem cells (BTSC) and their somatic counterparts in the brain, neural stem cells (NSC). To target the common pathways that play essential roles for survival of both BTSC and NSC, however, may eradicate both stem cell types. A better strategy would be to uncover the mechanisms that specifically regulate initiation of brain tumors and maintenance of the stem-like phenotype of BTSC. In this study, we hypothesized that formation of secondary DNA structure, G-quadruplex, is disrupted only in BTSC and targeting G-qudruplex results in eradication of BTSC without sacrificing the normal counterpart.
Experimental procedures: The effect of the G-quadruplex stabilizer, telomestatin was investigated on survival and proliferation of 3 different cell types; patient-derived BTSC, non-stem tumor cells derived from the matched samples, and normal neural precursors derived from fetal brains. We then investigated the mechanism of telomestatin action in BTSC. Lastly, we performed xenotransplantation of tumor cells pretreated with telomestatin into immunodeficient mouse brains to verify the effect of telomestatin on in vivo tumor growth.
Results: Treatment of patient-derived BTSC with telomestatin resulted in inhibition of proliferation and induction of apoptosis in vitro, and this phenotype was partially rescued by pretreatment with the PARP-1 inhibitor, suggesting that the action of telomestatin in BTSC is likely dependent on the PARP-1 pathway. In contrast, treatment of normal precursors with the same dose of telomestatin did not significantly affect their survival and proliferation. Growth of a glioma cell line in vivo was decreased by pretreatment with telomestatin.
Conclusions: Differential susceptibility of BTSC, compared to the normal counterpart, to telomestatin treatment indicates the significance of G-quadruplex structure in malignant gliomas and their tumor stem cells. Currently, we are investigating the effect of telomestatin treatment on mouse brain tumors derived from patient BTSC. The novel strategy targeting molecular aberrations in BTSC may offer innovative therapeutic approaches for malignant gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3327.
Abstract 3328: Cytotherapy with naïve rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases mouse survival in syngeneic mice
Authors: Doi Chiyo , Maurya Dharmendra K. , Pyle Marla , Troyer Deryl , Tamura Masaaki 
Published: February 2011

Abstract
Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. It is the fourth leading cause of cancer-related morbidity and mortality in the United States. MSC derived from the human umbilical cord matrix (UCMSC) have a great potential for therapeutic use in cancer. UCMSC-based targeted gene/therapeutic-delivery and successful tumor attenuation has been demonstrated. However, the targeted stem cell therapy would be significantly safer and more applicable to human patients if unmodified postnatal stem cells alone were shown to cause tumor cell death and regress tumors, without any foreign gene transfection. Accordingly, the aim of this study was to determine the anti-cancer effect of un-engineered naïve rat UCMSC on the growth of murine pancreatic ductal carcinoma in vitro and in vivo. A mouse peritoneal model was used to test the ability of un-engineered rat UCMSC to control growth of pancreatic cancer. In addition, MTT, direct cell count, [3H] thymidine uptake, and soft agar colony assays were carried out as in vitro studies. Co-culture of rat UCMSC with PAN02 murine pancreatic carcinoma cells (UCMSC:PAN02, 1:6 and 1:3) caused G0/G1 arrest and significantly attenuated the proliferation of PAN02 carcinoma cells as monitored by MTT assay, direct cell counts, and [3H] thymidine uptake assay. Rat UCMSCs also significantly reduced PAN02 colony size and number as measured by soft agar colony assay. The in vivo mouse studies showed that rat UCMSC treatment significantly decreased the peritoneal PAN02 tumor burden 3 weeks after tumor transplantation and increased mouse survival time. Histological study revealed that intraperitoneally administered rat UCMSC survived for at least 3 weeks and the majority were found near or inside the tumor. These results indicate that naïve rat UCMSC alone remarkably attenuate the growth of pancreatic carcinoma cells in vitro and in a mouse peritoneal model. Thus, these studies imply that UCMSC could be a potential tool for targeted cytotherapy for pancreatic cancer. This work was supported by Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU College of Veterinary Medicine Dean's fund, Kansas State Legislative Appropriation, NIH P20RR017686, P20RR015563 and R21 CA135599.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3328.
Abstract 3330: Nanog, cancer stem cells, and resistance to chemotherapy
Authors: Wang Man-Tzu , Nie Daotai 
Published: February 2011

Abstract
It has been increasingly appreciated that cancer stem cells are responsible for initiating tumor formation as well as resistance to chemoradiotherapy, but the mechanisms involved remain unknown. Nanog is a transcription factor essential for self-renewal of embryonic stem cells. The expression of Nanog has been reported in some cancer cells but its role in tumor initiation and resistance to chemotherapy has not been convincingly demonstrated. Herein, we report that Nanog is expressed in tumorigenic prostate cancer cells and further it plays an essential role of Nanog in tumor formation and resistance to chemotherapy. Enrichment for Nanog-expressing tumor cells led to an increase in the number of cells positive for stem/progenitor markers, increased clonogenic growth, and increased ability to form prostaspheres. When injected into mice, enriched Nanog-expressing cells formed tumors earlier and formed larger tumors than the vector control cells did. Knockdown of Nanog in tumorigenic cancer cells, via small hairpin RNAs, reduced clonogenic growth, stimulated epithelial differentiation, and significantly compromised their tumor initiating ability. Prospective enrichment of tumor cells with endogenous Nanog expression also led to enrichment of tumor cells resistant to Taxol, vinblastine, and doxorubicin, but not camptothecin (CPT). The increased resistance in Nanog expressing cells was attenuated, but not abolished, by inhibitors of p-glycoprotein, the ATP-bind cassette efflux transporter B1 (ABCB1), or by knockdown of ABCB1 via small hairpin RNAs (shRNAs). Expression of ABCB1 was increased in tumor cells enriched with endogenous Nanog expression while knockdown of Nanog reduced the expression of ABCB1 and sensitized tumor cells toward chemotherapeutics. Taken together, the data from gain-of-function and loss-of-function studies suggest an essential role of Nanog for prostate cancer cells to self-renew or propagate, to initiate tumor formation, and to resist chemotherapy via regulating the expression of ABC transporters.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3330.
Abstract 3337: Characterization of tumor initiating cells response to chemotherapy in human colorectal cancer
Authors: da Silva-Diz Victoria , Riba-Artés Diana , Gausachs Mireia , Urpí María , Capella Gabriel , Salazar Ramón , Villanueva Alberto , Muñoz Purificación 
Published: February 2011

Abstract
Current chemotherapy for colorectal cancer is still based in combined 5-fluorouracil (5-FU) and oxaliplatin administration with or without other new drugs. However, an important percentage of patients show resistance to this treatment. Tumor initiating cells (TICs) or cancer stem cells, are able to reconstitute a tumor of similar characteristics to the primary tumor after transplantation into immunodeficient mice. TICs show the ability to self-renew and give rise to non-TIC progeny, supporting the tumor growth. Recent studies suggest that TICs may be intrinsically resistant to therapy, leading to tumor relapse after chemotherapy. To gain insight into the dynamics of TICs during tumor progression and in response to chemotherapy, we have orthotopically implanted and perpetuated in nude mice 14 human colorectal carcinomas (CRC) that produce local and distal dissemination. We have characterized the chemotherapy response in 7 of these perpetuated xenografts. Four of these tumors showed a significant reduction of growth after 5-FU and oxaliplatin combined treatment (FUOX treatment) compared to the correspondent non-treated control tumors. To evaluate the role of TICs in chemotherapy response, we analyzed survival of non-TICs and TICs -identified by CD133/CD44/EpCAM cell surface markers- after chemotherapy. Our results show that, although in 2 out of 4 of the tumors showing efficient response to chemotherapy, TICs were more resistant to FUOX than the rest of tumor cells, in the other 2 tumors TICs and non-TICs were similarly sensitive to treatment. These results indicate that the resistance to chemotherapy is not an intrinsic characteristic of TICs and offer the possibility to characterize sensitive and resistant TICs to FUOX to identify genes and pathways directly involved in chemoresistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3337.
Abstract 3338: DLK1 could be a potential target against the cancer stem/progenitor cells of hepatocellular carcinoma
Authors: Xu Xiao , Zhang Xin , Liu Rui-Fang , Huang Li-Yu , Chen Fei , Han Ze-guang 
Published: February 2011

Abstract
Introduction: DLK1 is considered to play a vital role in the development of liver, and the oncogenesis and progress of hepatocellular carcinoma (HCC). It has been reported that mouse DLK1(+) fetal hepatic cells are able to differentiate into hepatocytes and biliary epithelial cell lineages and exhibit more proliferative than DLK1(−) cells. Recently, some studies demonstrated that DLK1 was frequently up-regulated in HCC, concomitant with known potential cancer stem/progenitor markers, and ectopic DLK1 promoted the proliferation of HCC cells. However, the biological behaviors of DLK1(+) HCC cells remain largely unknown, and whether DLK1 as a membrane protein could serve as a potential therapeutic target for HCC need further investigation.
Methods: The proportion of DLK1(+) cells in HCC cell lines was evaluated by flow cytometry. Both DLK1(+) and DLK1(−) cells were isolated by fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), respectively. Self-renewal, chemoresistance, colony formation and spheroid colony formation ability of the two cell populations were evaluated. In vivo tumorigenicity experiment was performed in BALB/c nude mice or NOD/SCID mice. In addition, cell proliferation, colony formation, spheroid colony formation assays and tumorigenicity experiments were also employed to assess the effect of RNA interference against DLK1 on HCC cells.
Results: DLK1(+) population was less than 10 percentage of all 10 HCC cell lines examined by flow cytometry analysis. Interestingly, DLK1(+) HCC cells sorted by FACS or MACS showed stronger ability of chemoresistance, colony formation and spheroid colony formation in vitro, and increased tumorigenicity ability in vivo, as compared with DLK1(−) cells. The DLK1(+) HCC cells with the property of self-renewal could generate differentiated progeny without DLK1 expression. Furthermore, DLK1 knockdown by adenovirus-mediated short hairpin RNA interference could significantly suppress the ability of proliferation, colony formation and spheroid colony formation, as well as in vivo tumorigenicity of HCC cells.
Conclusion: DLK1(+) human HCC cells are endowed with characteristics similar to those of cancer stem/progenitor cells. RNA interference against DLK1 can suppress the tumorigenicity of HCC cells, possibly through inhibiting the malignant behaviors of cancer stem/progenitor cells, which suggested that DLK1 could be a potential therapeutic target against the HCC stem/progenitor cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3338.
Abstract 3340: Salinomycin displays more potent anticancer effect against brain tumor stem cells than temozolomide
Authors: Alonso Marta M. , Gomez-Manzano Candelaria , Vaillant Brian , Xu Jing , Liu Dan , Jiang Hong , White Erin J. , Colman Howard , Fueyo Juan 
Published: February 2011

Abstract
Background: Salinomycin has recently proven to be highly effective against a model of breast cancer stem cells in vitro and in vivo. Moreover, treatment with this compound induced epithelial differentiation of tumor cells. A population of Brain Tumor Stem Cells (BTSCs) has been identified in malignant brain tumors. This population of cells has been found responsible for the initiation of these malignancies and may constitute the cause of resistance of malignant brain tumors to chemotherapy and radiotherapy and therefore responsible for the lethal recurrence after surgery. We hypothesize that salinomycin could be successfully implemented for the treatment of brain tumors and specifically for the eradication of BTSCs.
Material and Methods: In vitro cytotoxic effect of salinomycin or TMZ was assessed in a panel of BTSCs lines (n=11), established glioma cell lines (n=4) and normal human astrocytes (NHA) by MTT. Self-renewal was assayed by single cell plating and limited dilution assay. Cell cycle was evaluated by flow cytometry using PI staining. In addition, we performed QT-RT-PCR and western blot analysis to assess the expression of different stem cells markers before and after the treatment. In addition, global gene expression analysis was performed using an affymetrix array. Survival studies in animal models are in progress.
Results: Our results showed that salinomycin presents a potent antitumoral effect against BTSCs and glioma cell lines. Importantly, salinomycin displayed an IC50 ranging from 100 to 10000 folds lower than TMZ (currently the gold standard treatment for malignant brain tumors) in the same cell lines. Interestingly, salinomycin reduced the number of self-renewal cells in treated-BTSCs. This was confirmed with the decreased in the expression of stem cell markers such as Sox2 and Bmi1. Cell cycle analysis showed that unlike TMZ treated cells, which arrest in G2, salinomycin treated cells did not experienced growth arrest and progress through the cell cycle to end up dying.
Conclusions: Altogether our data show that salinomycin is more potent than temozolomide for the treatment of brain tumor stem cells and therefore could be a promising agent against malignant brain tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3340.