bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2117: The Wnt inhibitory factor 1 (WIF-1) has tumor suppressing functions in glioblastoma potentially by inducing cellular senescence
Authors: Vassallo Irene , Lambiv Wanyu , Delorenzi Mauro , Shay Tal , Diserens Annie-Claire , Misra Anjan , Feuerstein Burt , Murat Anastasia , Migliavacca Eugenia , Hamou Marie-France , Domany Eytan , Stupp Roger , Hegi Monika E. 
Published: July 2012

Abstract
Glioblastoma multiforme is the most aggressive form of human glioma and despite recent progress in therapy the prognosis remains dismal with a median survival of 15 months. Expression based prediction of gene alterations identified Wnt inhibitory factor I (WIF1) as a new candidate tumor suppressor gene involved in glioblastoma. WIF1 encodes a secreted Wnt antagonist and it was strongly down-regulated in most glioblastoma as compared to normal brain, implying deregulation of Wnt signaling. Silencing of the WIF1 gene was found to be mediated by deletion and WIF1 promoter hypermethylation. Ectopic expression of WIF1 in glioblastoma cell lines revealed a dose dependent decrease of Wnt pathway activity. To further dissect the biological effects of WIF1 re-expression, we established WIF1 overexpressing glioblastoma cell lines. We observed that WIF1 re-expression inhibited cell proliferation in vitro and strongly reduced anchorage independent growth. The ability of forming colonies in soft agar was reduced to less than 11% of the control. Moreover, the expression of WIF1 was able to completely abolish tumorigenicity in a respective xenograft model in nude mice. Interestingly, WIF1 overexpression in glioblastoma cells induced a senescence-like phenotype characterized by the appearance of enlarged flattened and multinucleated cells positive for the presence of β-galactosidase, a late marker of senescence. These results provide evidence that WIF1 has tumor suppressing properties in glioblastoma, hence, the implication of a deregulated Wnt pathway may render glioblastoma sensitive to Wnt signaling inhibitors, potentially by diverting the tumor cells into a senescence-like state.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2011-2117
Abstract 2128: Salvianolic acid B inhibits both ER-α +/- breast cancer cell growth in vivo and in vitro
Authors: Sha Wei , Gu Xinbin , Guo Yinhan , Wang Paul , Sukumar Saraswati , Zhou Yanfei 
Published: July 2012

Abstract
PURPOSE: Estrogen receptor α negative (ER-α/-) breast cancer cells are found to respond poorly to chemotherapeutic agents. Salvianolic acid B (Sal-B) is an active depside compound isolated from Salvia miltiorrhiza Bge, which is a well-known Chinese medicine that has been widely used to treat various disorders including cancers. In this study, we evaluated the anti-cancer activity of Sal-B leading to ceramide-mediated apoptosis in ER-α + and ER-α – cancer cell lines. DESIGN METHODS: Using MCF-7-luc (ER-α/+) and MDA-MB-231-luc (ER-α/-) human breast cancer cell lines as a test model, cell-based bioluminescence assay and colony assay for cell viability, Western Blot analysis for ER-α and apoptosis-related proteins expression, flow cytometry analysis for cell cycle, and tumor xenografts were performed. RESULTS: Significant decreased cell viabilities (p&lt;0.05) were observed in Sal-B treated ER-α + and ER-α – cells. The expression of anti-apoptotic proteins (Bcl-2, Bcl-XL and surviving) and ceramide metabolism enzymes (GCS and GM3 synthase) all markedly decreased. Sal-B treatment suppressed cell cycle related protein expression, such as cyclin A and B. Further analysis using flow cytometry confirmed these observations. The tumor size was significantly lower in Sal-B treated MDA-MB-231-luc cells transplanted mice group compared to untreated control group and doxorubicin treated group. CONCLUSION: Sal-B effectively inhibits the growth of cultured ER-α +/- cell lines and MDA-MB-231-luc tumor xenografts. In addition, Sal-B is able to modulate ceramide-mediated apoptosis by inhibiting ceramide metabolic enzymes (GCS and GM3 synthase). Thus, Sal-B has high potential to be a new therapeutic strategy to improve ER-α/- cancer treatment. Research supported in part by grants P20 CA118770 and U54 CA091431 from NCI/NIH and 2G12 RR003048 from the RCMI Program/NCRR/NIH.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2128. doi:10.1158/1538-7445.AM2011-2128
Abstract 2132: Deferoxamine and Deferasirox enhance anticancer effects of apoptosis in gastric cancer cells
Authors: Oh Go Oun , Kang Myoung-Hee , Kang Han-Na , Kim Jung-Lim , Kim Jun-Suk , Oh Sang-Cheul , Yoo Young-A Yoo , Lee Seung-Young Lee 
Published: July 2012

Abstract
Deferoxamine(DFO) and Deferasirox(DFRA) is an iron chelating agent that has been used extensively to treat acute iron detoxification and chronically iron overloaded patients. Recent reports have been shown that iron chelators induce anti-proliferative effect in multiple leukemia cells. However, their roles and the underlying mechanism in anti-tumorigenic function of solid tumor, especially gastric cancer, are not yet known. In this work, we evaluated the anti-tumorigenic action of these two iron chelating agent with gastric cancer cell line, and investigated their apoptosis-inducing effects as the potential mechanism in this process.
The results show that both of them induce the growth inhibitory effects in both dose- and time-dependent fashion in gastric cancer cell line AGS and SNU-638. Cell cycle analysis by FACS indicated that both DFO/DFRA-treated cell lines showed an increase in the proportion of cells in sub-G1 phase, compared to untreated cells. Exposure of gastric cancer cells to DFO/DFRA also resulted in the increase in the percentage of annexin V- positive and PI-negative cells. The results by multiple in vitro experimental model, showed that DFO /DFRA induce these gastric cancer cells to undergo apoptosis with a release of cytichrome C from mitochondria, the activation of caspase-3/9, the cleavage of PARP, the cleavage of anti-apoptotic protein Bcl-2, together with the accumulation of pro-apoptotic protein Bax and Bim. Furthermore, knock-down of Bax and Bim expression by RNA interference virtually eliminated DFO/DFRA-induced apoptosis. Importantly, inhibition of JNK kinase activity demonstrated that DFO/DFRA-induced apoptotic pathway was regulated by the JNK signaling cascade
In conclusion, this finding indicates that iron-chelating agent, DFO and DFRA, promotes apoptosis of gastric cancer cells by sequential activation of the JNK signaling pathway followed by the up-regulation of intrinsic pathway of Bax/Bim-caspase 3/9.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2132. doi:10.1158/1538-7445.AM2011-2132
Abstract 2133: Phenylenebis(1,2-ethanediyl)bisisoselenourea (PBISe), a novel selenium drug for the treatment of hepatocellular cancer (HCC)
Authors: Tagaram Hephzibah R. , Desai Dhimant , Ongsansoy Sherwin , Dasari Anthia P. , Gowda Kavitha , Liu Dai , Liu Guangfu , Amin Shantu , Staveley-O'Carroll Kevin 
Published: July 2012

Abstract
Hepatocellular cancer (HCC) is an aggressive tumor that frequently arises in a setting of chronic liver disease and cirrhosis. Appearing 20 to 30 years from initial insult, it is more likely to be discovered in its late stage. The median survival following diagnosis is approximately 6 to 20 months. Although the definitive treatment is tumor resection, most patients are not eligible because of tumor extent or underlying liver dysfunction. Alternative chemopreventive approach in reducing HCC mortality is to be explored. Earlier we have shown the efficacy of PBISe against colon adenocarcinoma and metastatic melanoma with a negligible systemic toxicity in animal studies. In the present study, we intend to demonstrate the chemotherapeutic effects of PBISe on the human HCC. We analyzed the role of PBISe and the underlying mechanism in HCC. PBISe in our study suppressed cell growth, and induce apoptosis. Evaluation of PBISe was performed in vitro on human SK-HEP-1, HepG2, C3A and HUH-7 cells by cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation by Tunnel, cell cycle analysis and AKT, ERK, STAT, SAPK/JNK phosphorylation. PBISe promotes apoptosis by upregulating caspase 3/7, annexin-V, and cPARP. Increased DNA fragmentation was observed with PBISe in all the HCC cell lines tested. PBISe also mediated the cellular proliferation by AKT signaling and downstream pPRAS40 by inducing the cell cycle arrest at G2-M phase. Decreased pERK, pSTAT and pAKT shows that PBISe has a potential to target several signaling pathways. Overall our results suggest that PBISe is a potent chemotherapeutic agent with novel properties for the treatment of HCC. The chemotherapeutic effect of PBISe in the murine HCC model will be discussed. Supported by Penn State Deans Feasibility Grant to H.R.T, NIH RO3 CA 137763-01 to D. D., NIH KO8 417-67HY to K.S.O.C.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2133. doi:10.1158/1538-7445.AM2011-2133
Abstract 2138: Vinblastine acutely sensitizes hematopoietic cancers to Bcl-2 targeting drugs
Authors: Bates Darcy J.P , Lowrey Christopher , Eastman Alan 
Published: July 2012

Abstract
Chronic lymphocytic leukemia (CLL) characteristically maintains high levels of the anti-apoptotic protein Bcl-2, thus protecting them from apoptotic death and leading to an accumulation of mature resting B cells. Many other hematopoietic malignancies including acute promyelocytic leukemia (APL) also depend upon Bcl-2 family proteins for survival, suggesting that Bcl-2 proteins are excellent targets for anti-cancer therapies. We have previously shown that some leukemia and lymphoma cell lines undergo rapid apoptosis (≤6 h) when incubated with the microtubule disrupting agent vinblastine. Several other cell lines undergo this rapid apoptosis when vinblastine is combined with various approaches that target the anti-apoptotic proteins Bcl-2 or Mcl-1. These approaches include incubation with ABT-737 that inhibits Bcl-2 and Bcl-X, and SCH727965 (dinaciclib) that inhibits CDK7/9, thereby inhibiting translation which results in rapid loss of Mcl-1. In this study, we have assessed the ability of these agents alone or in combination to induce apoptosis in freshly isolated CLL and APL cells. Incubation with vinblastine alone induced variable apoptosis within 6 h (5-60%). ABT-737 induced rapid and almost complete apoptosis in CLL and in 50% of APL cells ex vivo. However, when combined with vinblastine, a 10-fold lower concentration of ABT-737 was required to induce complete apoptosis. Dinaciclib alone also induced variable levels of apoptosis (5-90%), but again the combination with vinblastine induced extensive apoptosis at lower concentrations of both drugs. Normal peripheral blood mononuclear cells were resistant to single agent or combination treatments. Sensitivity to ABT-737, dinaciclib or vinblastine was independent of CD38 and ZAP70 status and previous clinical treatment (untreated or relapsed patients). These results suggest that combinations of vinblastine and ABT-737 or dinaciclib are more effective than single agent therapy. Furthermore, these combinations may overcome resistance to individual drug therapies in patients with CLL or APL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2138. doi:10.1158/1538-7445.AM2011-2138
Abstract 2140: Assessment of curcumin-induced apoptosis and detection of cancer stem cell-like subpopulations in human esophageal cancer cell lines
Authors: Al Manaa Taghreed N. , Geusz Michael E. , Jamasbi Roudabeh J. 
Published: July 2012

Abstract
Curcumin, the major active ingredient of turmeric, has been shown to kill several types of malignant cells while it has little or no effect on normal cells, suggesting that it may be an effective therapeutic agent. Although some studies have investigated curcumin effects on esophageal cancer cell lines, no studies have characterized the curcumin-surviving cells, an important population that might show resistance to curcumin. There is increasing evidence that many cancers contain subpopulations that display stem cell characteristics. Cancer stem cells (CSCs) appear to play a central role in tumorigenesis, recurrence, metastasis, and resistance to cancer therapy. The aims of the current study were to assess curcumin-induced cell death and detect CSC subpopulations in six human esophageal cancer cell lines (TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2). Aldehyde dehydrogenase-1A1 (ALDH1A1) expression was used as one marker for CSCs. To evaluate curcumin effects, the cell lines were exposed to 20-80 µM of curcumin for 30 hrs. In all six lines, cell death increased continuously with increasing dosage of curcumin based on a standard crystal violet assay. No cells survived at 80 µM, and the range of cell death across the six cell lines was 66 to 89% at 60 µM. To characterize the progeny of cells that survived curcumin, 1×105 cells from each line were exposed to 40-60 µM curcumin for 30 hours, and the colonies that formed from surviving cells were counted. The number of colonies present after 60 µM treatment varied between the cell lines (ranging from 8 to more than one hundred). The Yes-2 cell line did not survive at 60 µM, but produced 15 colonies after 40 µM treatment. Staining with an antibody against ALDH1A1 was used to compare CSC-like subpopulations within and among the original cells lines as well as cell lines established from the curcumin-treated lines. All cell lines were heterogeneous with respect to ALDH1A1 staining, revealing two subpopulations within each line. The intensity of staining was at least two times higher in the population considered to be CSCs. Interestingly, the curcumin-surviving cell lines showed a significant loss in the high-staining population compared to the untreated cells (T-test, p&lt;0.05), suggesting that curcumin not only can kill cancer cells but also CSCs. Thus, esophageal CSCs appear to be highly sensitive to curcumin. Therefore, curcumin may be a more effective compound for esophageal cancer therapy than other chemotherapeutic agents.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2140. doi:10.1158/1538-7445.AM2011-2140
Abstract 2141: The differential apoptotic responses of normal breast cells versus luminal and triple negative breast cancer cells to chemotherapeutic agents
Authors: King Jamie L. , Gurley Kashenya M. , Rorie Checo J. 
Published: July 2012

Abstract
Triple negative breast cancer is characterized by the loss or low expression of estrogen receptor, progesterone receptor, and HER2 proteins which have been targeted and established as somewhat effective therapy regiments in other breast cancer subtypes including luminal tumors. Since triple negative tumors are missing these established drug targets, there has been little advancement in the establishment of targets in this breast cancer subtype. Triple negative breast cancer is described as aggressive due to their invasiveness and metastatic properties. One potential mediator of triple negative breast cancer aggressive behavior may be due to the fact this breast cancer subtype may have as high as an 80% p53 tumor suppressor gene mutation rate. While p53 may be mutated at high rates, it may be possible to design drugs to target some of the downstream genes that p53 transactivates, including the cyclin dependent kinase inhibitor p21 and the pro-apoptotic gene PUMA, in order to inhibit the further growth of the triple negative breast cancer cells. Here, we stressed a normal breast cancer control, luminal subtype, and triple negative subtype cancer cell lines with Actinomycin D, doxorubicin, and staurosporine. We show that all cell lines responded to the various DNA damaging agents via apoptosis as observed by light microscopy and by PARP cleavage using Western blot analysis. Interestingly, the “normal” breast cell line, AG1132, showed a delayed apoptosis response to doxorubicin treatment as compared to the breast cancer cell lines, HCC1806, HCC70, and HCC1500. We are monitoring the p53 tumor suppressor pathway network in all of these cells to determine its integrity and whether there is a direct or indirect involvement of p53 on the apoptosis responses. We are also further analyzing the chemotherapeutic agents to determine their effectiveness in killing breast cancer cells with limited cytotoxic effects to normal breast cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2011-2141
Abstract 2144: Characterization of HMGB1-induced cell death in colon carcinoma cells
Authors: Gdynia Georg , Keith Martina , Schirmacher Peter , Roth Wilfried 
Published: July 2012

Abstract
The danger protein HMGB1 induces a distinct form of cell death in cancer cells which is different from classical necrosis, apoptosis, autophagy, or senescence. Interestingly, colon carcinoma cells are less sensitive for the cytotoxic activity of HMGB1 than other types of cancer cells. The aim of this study was to characterize the molecular and metabolic pathways regulating the susceptibility to HMGB1 in colorectal carcinoma. Stable ectopic over-expression of HMGB1 inhibited significantly the proliferation of colon carcinoma cells. Treatment of cells with recombinant human (rh) HMGB1 induced significant cytotoxicity in a concentration range of 80 – 200 nM. Cancer cells depleted of mitochondrial DNA were less susceptible to the cytotoxic effects of rhHMGB1. In ATP luciferase assays, after 72 h of incubation with rhHMGB1 a significant depletion of intracellular ATP was observed, paralleled by the formation of giant mitochondria. RhHMGB1 modulated the specific activity of the mitochondrial respiratory enzymes and the electron flux in the electron transport chain in a dose-dependent manner. Interestingly, addition of NAD+, L-pyruvate, or ATP did not protect the cells from rhHMGB1-induced cell death. RhHMGB1-induced mitochondrial and metabolic events were further characterized by tracking radioactive glucose and pyruvate isotopes. In summary, the HMGB1 protein induces a novel form of cell death in diverse types of cancer cells. In colon cancer cells, HMGB1 modulates the activity of the mitochondrial respiratory enzymes leading to a change in glycolytic flux and a strong depletion of intracellular ATP. These observations implicate a new functional link between the HMGB1 protein and mitochondrial respiratory regulation as well as glycolysis activity in cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2144. doi:10.1158/1538-7445.AM2011-2144
Abstract 2145: AR-42, a novel histone deacetylase inhibitor with selectivity against leukemia stem cell via apoptosis induction, inhibition of chaperone function of heat shock protein 90 in acute myeloid leukemia
Authors: Yang Neng , Hassane Duane C. , Balys Marlene , Corbett Cheryl A. , Jordan Craig T. , Guzman Monica L. 
Published: July 2012

Abstract
AML is a fatal disease where most patients relapse and die of their disease. Increasing evidence indicates that disease relapse is driven by leukemia stem cells (LSCs). Thus, it is imperative to identify new therapies that can ablate LSCs. We have previously reported that screening the NCBI Gene Expression Omnibus (GEO) can accelerate the identification of anti-LSC compounds by searching for those mimicking the gene expression pattern of a known anti-LSC compound, parthenolide (PTL). One of our “hits” was the HDACi, AR-42 (Arno Therapeutics, Inc). This compound represents a novel class of HDACis that are structurally similar to phenylbutyrate, but with improved HDACi activity at sub-micromolar concentrations.
At first, we investigated effects of AR-42 on growth and colony forming ability by using AML cell lines and primary human AML samples. AR-42 exhibits low micromolar potency in biochemical and cellular assays. AR-42 efficiently suppressed AML cell growth at a low dosage (1 μM) after 24 hours of treatment. Just like PTL, AR-42 preferentially targets AML progenitor and stem cell populations. More than 50% cell death was induced by AR-42 in phenotypically defined AML stem / progenitor. Colony forming capability of LSCs treated with 1 μM AR-42 for 24 hours was significantly diminished. Furthermore, 1 μM AR-42 significantly impaired the potential of LSCs in a nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenograft model.
Surprisingly, even though AR-42 partially mimics the gene expression pattern of PTL, it does not activate Nrf2-controlled cytoprotective responses like PTL. AR- 42 inhibits NF-κB but, unlike PTL, does not activate HMOX-1. AR-42- mediated apoptosis is associated with activation of caspase 8, PARP cleavage. Further studies found that AR-42 induced inhibition of HSP90 in conjunction with degradation of FLT3 protein. Altogether, these findings indicate that AR-42 may be a promising LSC-targeted therapeutic agent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2145. doi:10.1158/1538-7445.AM2011-2145