bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 421: Epidermal growth factor-like repeats of tenascin C alter melanoma cell migration both directly and through alteration of the ECM
Authors: Grahovac Jelena , Wells Alan 
Published: July 2012

Abstract
In melanoma, the most aggressive type of skin cancer, invasion through the extracellular matrix (ECM) is a harbinger of dissemination and mortality. Highly upregulated in both primary invasive and metastatic melanoma is tenascin C (TNC), a hexameric ECM protein with a multidomain structure composed of the globular N-terminal domain, 14.5 epidermal growth factor (EGF)-like repeats, fibronectin-III like repeats and the C-terminal globular fibrinogen-like domain. Our group previously showed that the EGF-like repeats of TNC are able to bind the EGF receptor (EGFR) with μM affinity and preferentially activate the motogenic signaling cascades. Both normal melanocytes and melanoma cells migrate faster on surfaces coated with TNC. Therefore, we hypothesize that the increased levels of TNC in melanomas promote tumor cell migration and invasion heralding dissemination through enhanced EGFR signaling. We expressed EGF-like repeats of TNC (TNC-EGFL) in melanoma cell lines already expressing endogenous TNC and observed change in the cell morphology, and more importantly a prominent anti-adhesive phenotype. TNC-EGFL expressing cells attached with a four-hour lag compared to parental cell lines and detached to a greater extent in inverted centrifugation adhesion assays. This was not due to decreased viability of TNC-EGFL expressing cells as determined by dye exclusion assay. As this phenotype could not be reverted by adding anti-EGFR antibody, we speculate that EGFR signaling might be intracellular. In two-dimensional migration assays, TNC-EGFL expressing cells closed a gap more slowly, possibly due to inability to properly attach during migration, emphasizing the need of concerted action of different TNC domains in regulating migration. On the other hand, quantitative PCR array analysis of a panel of ECM and adhesion molecules revealed changes in matrix metalloproteinase (MMP) expression, specifically MMP-2, MMP-9 and MMP-14, and increase in TGF β1 expression, proteins associated with melanoma invasiveness and vasculogenic mimicry. These results imply that TNC-EGFL repeats are involved in melanoma invasion both by directly influencing cell migration and indirectly by altering the tumor microenvironment and may have implications for development of anti tumor therapies directed at the extracellular matrix.
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 421. doi:10.1158/1538-7445.AM2011-421
Abstract 4212: Prevention of estrogen-induced breast cancer by antioxidants: Role of N-quinone oxidoreductase 1 (NQO1)
Authors: Bhat Hari K. , Singh Bhupendra 
Published: July 2012

Abstract
The importance of estrogens in the etiology of breast cancer is widely recognized. However, the exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. The objective of the current study was to characterize the role of NQO1 in the prevention of estrogen-induced DNA damage and mammary tumorigenesis by antioxidants vitamin C or butylated hydroxyanisole (BHA). NQO1 converts 17β-estradiol (E2)-quinones back to E2-catechols, thus making E2-quinones unavailable for oxidant damage. Female ACI rats were treated with E2 (3 mg); vitamin C (1% in drinking water); E2 + vitamin C; BHA (0.7% in diet); and E2 + BHA for up to 8 months. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. No tumors were detected in the sham control, vitamin C and BHA treatment groups whereas in the E2 + vitamin C, E2 + BHA, and E2 treatment groups, the breast tumor incidences were 29, 24 and 82% respectively. mRNA and protein expression of NQO1 was analyzed in breast and breast tumor tissues of rats treated with E2 and antioxidants vitamin C or BHA. NQO1 was suppressed in E2-exposed mammary tissue after treatment of rats with E2 for 8 months and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. NQO1 enzyme activity was unchanged in mammary tissue of rats from all the treatment groups. However, NQO1 enzyme activity was decreased in E2-induced mammary tumors. Catechol-O-methyltransferase (COMT) activity was unchanged in the mammary tissue of all the groups except in the E2-treated group. Vitamin C or BHA co-treatment significantly decreased E2-mediated increase in 8-hydroxydeoxyguanosine (8-OHdG, an oxidative DNA damage marker) levels in mammary tissue. To investigate the relationship between NQO1 and 8-OHdG damage, human breast epithelial cell line MCF10A was treated with E2, vitamin C, BHA, dicumarol (NQO1 inhibitor), E2 + vitamin C, and E2 + BHA. E2 and dicumarol significantly increased 8-OHdG levels in MCF-10A cells whereas co-treatment with E2 and antioxidants reverted them back to the normal levels. Our studies suggest a protective role of NQO1 in E2-induced DNA damage and breast carcinogenesis. NQO1 may thus have a unique potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia.
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 4212. doi:10.1158/1538-7445.AM2011-4212
Abstract 4215: Apoptosis induction in breast cancer cell lines by the dietary flavonoid fisetin
Authors: Smith Matthew L. , Giacomantonio Carman , Hoskin David 
Published: July 2012

Abstract
Canadian women have a lifetime probability of diagnosis of breast cancer of approximately 1 in 9. Although the current management of breast cancer is effective, significant morbidity and mortality are associated with the disease and its treatments. Fisetin, a phytochemical present in many fruits and vegetables, has demonstrated anticancer activity for both prostate and colon cancer. This study explores fisetin as a possible novel therapeutic modality for breast cancer. Breast cancer cell lines (MDA-MB-468, MDA-MB-231, MCF-7, T47-D, SKBR-3; mitozantrone-resistant (MITX) and paclitaxel-resistant (Tx400) cell lines) were exposed to fisetin and cell survival was assessed by MTT, crystal violet, acid phosphatase, and colony-forming assays. Normal cells (human mammary epithelial cells, fibroblasts, human umbilical vein endothelial cells) were used as negative controls. The mechanism of action of fisetin was explored using cell cycle analysis and assays for apoptosis/necrosis, including Annexin V-propidium iodide staining, DNA fragmentation measured by JAM assay, and LDH-release assay. Apoptosis induction pathways were studied using Western blotting, as well as caspase inhibitors and cell viability assays. Flow cytometry was used to assess mitochondrial membrane stability (DiOC6 staining) and reactive oxygen species (ROS) production (dihydroethidium staining). Fisetin exhibited a dose- and time-dependent cytotoxic effect on breast cancer cell lines (e.g., 100 µM fisetin decreased MDA-MB-468 cell viability by 70% at 72h in both crystal violet and acid phosphatase assays). In contrast, the viability of normal cells was not substantially affected by concentrations of fisetin that killed breast cancer cells. Fisetin-treated breast cancer cells showed cell cycle arrest (MDA-MB-468 cells arrested at G2/M phase; MDA-MB-231 cells arrested in S-phase) and death by apoptosis (e.g., MDA-MB-468 cells showed up to 50% apoptosis and 8% late apoptosis/necrosis by Annexin V-staining; cell cycle analysis and LDH-release assays supported these results). Fisetin-induced apoptosis was associated with mitochondrial membrane permeabilization but did not involve caspase activation since Western blotting showed that caspase-3 was not cleaved in fisetin-treated breast cancer cells and cell viability was not preserved in the presence of a pan-caspase inhibitor. In addition, fisetin did not cause ROS production in MDA-MB-468 or 231 cells, indicating that ROS do not contribute to the cytotoxic effect of fisetin. Together, these findings suggest that fisetin may be useful in the treatment of breast cancer. Ongoing studies are using Zebra fish as a model to explore the in vivo anticancer activity of fisetin.
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 4215. doi:10.1158/1538-7445.AM2011-4215
Abstract 4228: Ganoderma lucidum (Reishi) reduces inflammatory breast cancer progression via protein synthesis inhibition
Authors: Rosario-Acevedo Raysa , Cubano Luis A. , Dharmawardhane Suranganie F. , Martinez-Montemayor Michelle M. 
Published: July 2012

Abstract
The anti-cancer effects of the medicinal mushroom Ganoderma lucidum (Reishi) were tested as a potential therapeutic for Inflammatory Breast Cancer (IBC). IBC is a rare, lethal and aggressive form of locally advanced breast cancer that manifests itself without a typical tumor mass. Studies suggest that the mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth via the regulation of protein synthesis. The mTOR effectors for protein synthesis are eukaryotic initiation factor 4E-binding protein 1 (4EBP-1) and the ribosomal protein S6 kinase (p70S6K). The 4EBP-eIF4E complex exerts control over cap-dependent translation, while p70S6K stimulates eIF4F translation of specific mRNAs with highly structured 5′UTRs, promoting cell growth, and tumor progression. In IBC the eukaryotic initiation factor, eIF4GI is overexpressed, which reprograms protein synthesis for cap-independent translation via increased initiation of internal ribosome entry site (IRES)-dependent translation. eIF4GI increased mRNA translation is partly responsible for the unique IBC pathological properties: overexpression of E-cadherin, strong homotypic IBC cell interaction, and formation of tumor emboli to promote IBC cell invasion. Using the patient derived IBC cell line, SUM 149, we previously demonstrated that Reishi extract selectively inhibits IBC cell growth and invasion by downregulating the expression of genes involved in invasion, survival and proliferation, and the protein expression of E-cadherin. The present study demonstrates that Reishi extract reduces the expression of AKT, which signals to activate the translational machinery by mTOR. Reishi extract reduced the expression of p70s6K and eIF4G, and diminished the expression of the IRES dependent mRNA containing proteins: c-Myc, p120 catenin, vascular endothelial growth factor (VEGF), BCL-2 and BCL-XL. Furthermore, Reishi extract reduced the expression of eIF4E and the phosphorylation of its inhibitor, 4EBP-1. Our results provide evidence that Reishi suppresses protein synthesis potentially by both cap-dependent and cap independent mechanisms. Our findings suggest that Reishi is a potential natural therapeutic that can be used in combination with traditional therapy to treat this intractable and deadly disease.
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 4228. doi:10.1158/1538-7445.AM2011-4228
Abstract 4229: Dichamanetin, a C-benzylated flavonoid from Piper sarmentosum inhibits cell growth and induces G1 cell cycle arrest in cancer cells through mitochondrial-mediated apoptosis
Authors: Matthew Susan , Pan Li , Shen Qi , Kinghorn A. Douglas , Swanson Steven M. , Carcache de Blanco Esperanza J. 
Published: July 2012

Abstract
Dichamanetin (C29H24O6) is a rare C-benzylated flavanoid isolated as a major metabolite from Piper sarmentosum Roxb. (Piperaceae). Dichamanetin significantly decreased the cell viability of various types of cancer cells in a dose- and time-dependent manner, characterized by G1 arrest of the cell cycle. In the present study, we investigated the molecular mechanism whereby dichamanetin exerts its cytotoxic effect on human cancer cells in vitro. We examined the involvement of ROS-signaling components (ROS levels, NF-kB transcription factor, mitochondrial membrane potential, DNA damage, and proteasome inhibition) and demonstrated that the antiproliferative effect of cancer cells is partially mediated by induction of oxidative stress. Dichamanetin treatment did not significantly inhibited proteasome, but inhibited moderately PARP-1 enzyme activity. Additionally, FACS analysis with JC-1 fluorescent dye established significant deviation of mitochondrial membrane potential by dichamanetin in treated cells. The present data therefore supports dichamanetin as an active anti-proliferative metabolite that acts in part through mitochondrial-mediated apoptosis.
Acknowledgment
This research was supported by Program Project Grant P01-CA125066 funded by the National Cancer Institute, NIH.
We also wish to acknowledge the plant taxonomists who collected the plant material used in this investigation.
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 4229. doi:10.1158/1538-7445.AM2011-4229
Abstract 4233: Protolimonoids potently suppress mitochondrial respiration and disrupt protein translation in breast tumor cells
Authors: Zhou Yu-Dong , Li Jun , Mahdi Fakhri , Du Lin , Datta Sandipan , Nagle Dale G. 
Published: July 2012

Abstract
Hypoxia (decreased oxygen tension) is a common feature of solid tumors and represents an obstacle for cancer treatment. The transcription factor hypoxia-inducible factor-1 (HIF-1) has emerged as an important molecular target for antitumor hypoxia drug discovery. A natural product chemistry-based approach was utilized to identify small-molecule HIF-1 inhibitors. Over 20,000 extracts of plants and marine organisms were evaluated for HIF-1 inhibitory activities. An active extract of the sacred medicinal Bael Tree (Aegle marmelos) trunk bark was subjected to bioassay-guided isolation and de-replication-based structure elucidation yielded two known protolimonoids skimmiarepin A (1) and C (2). Compounds 1 and 2 inhibited hypoxia-induced HIF-1 activation in a human breast tumor T47D cell-based reporter assay (IC50 values 0.063 and 0.068 μM, respectively). The hypoxic induction of HIF-1 target genes GLUT-1 and VEGF were also inhibited by 1 and 2. Mechanistic investigation revealed that 1 and 2 suppressed HIF-1 activation by blocking the accumulation of nuclear HIF-1α protein under hypoxic conditions. To test the hypothesis that these protolimonoids may interfere with hypoxic signaling by disrupting mitochondrial function, the effects of 1 and 2 on cellular respiration were examined. Both compounds inhibited T47D cell respiration at the range of concentrations that inhibited hypoxic HIF-1 activation. Compound 1 suppressed mitochondrial electron transport chain at complex I (NADH dehydrogenase). Under experimental conditions, neither 1 nor rotenone (positive control for complex I inhibitor) decreased cellular ATP content following a two-day exposure. However, rotenone and 1 suppressed cellular signaling pathways that control protein translation. While it is commonly believed that the antitumor activity of mitochondrial inhibitors is a consequence of their ability to inhibit cellular ATP production, the disruption of protein translation appears to constitute an important mechanism by which mitochondrial inhibitors obstruct tumor cell proliferation.
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 4233. doi:10.1158/1538-7445.AM2011-4233
Abstract 4235: Antiproliferative effects of cucurbitacin B in breast cancer cells: Down-regulate c-Myc/hTERT/telomerase pathway and obstruct the cell cycle
Authors: Duangmano Suwit , Dakeng Sumana , Jiratchariyakul Weena , Suksamrarn Apichart , Smith Duncan R. , Patmasiriwat Pimpicha 
Published: July 2012

Abstract
Abstract: Naturally occurring cucurbitacins have been shown to have anticancer, antimicrobial and anti-inflammatory activities. In this study, we determined the effects of cucurbitacin B extracted from Thai herb Trichosanthes cucumerina L. on the regulation of telomerase in three human breast cancer cell lines (T47D, SKBR-3, and MCF-7) and a mammary epithelium cell line (HBL-100). Cell viability after treatment with cucurbitacin B which is an active ingredient of this herb, was assessed by MTT assay and cell cycle analysis by flow cytometry. Telomeric Repeat Amplification Protocol (TRAP) assays and RT-PCR (qualitative and realtime) were performed to investigate activity of telomerase as well as expression of human telomerase reverse transcriptase (hTERT) and c-Myc. The c-Myc protein level was also determined in SKBR-3 and HBL-100. Our results show that the cucurbitacin B inhibits growth and telomerase activity in the three breast cancer cell lines and an obvious inhibitory effect was seen in the estrogen receptor (ER)-negative breast cancer cell SKBR-3 rather than ER-positive MCF-7 and T47D cells. The expressions of hTERT and c-Myc were also inhibited by cucurbitacin B, In addition, the reduction of c-Myc protein after the treatment was clearly observed in SKBR-3 cells even at the ten times lower concentration of cucurbitacin B compared to the concentration used for the HBL-100. DNA flow cytometric analysis indicated that treatment with cucurbitacin B resulted in G2/M arrest. These results imply that cucurbitacin B exerts anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression and arrest of the cell cycle at G2/M phase in breast 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 4235. doi:10.1158/1538-7445.AM2011-4235
Abstract 4261: Anti-angiogenic effects of zoledronic acid on osteotropic breast cancer cells
Authors: Contreras Cynthia , Hamud Walid , Dhakal Bishal , Khanal Bijay , Bush Jason 
Published: July 2012

Abstract
Emerging data suggest the bisphosphonate, zoledronic acid (ZOL), exerts both indirect and direct anti-tumoral effects by decreasing tumor cell proliferation, increasing apoptosis, and inhibiting angiogenesis. Recent data indicate that anti-angiogenic factors exert cellular effects via suppression of mitochondrial oxidative phosphorylation/respiration and elevation of intracellular ROS levels. This project intended to define proteins involved in response to ZOL-treatment of an osteotropic breast cancer cell line, MDA-231BO. Results demonstrate that MDA-231BO cells are more sensitive to ZOL cytotoxicity and salutary effects are both media- and calcium-dependent. To investigate pro-apoptotic mechanisms of ZOL, total RNA, whole cell protein lysates, or mitochondrial-enriched fractions were isolated from MDA-231BO cells and using a combination of RT-PCR, 1D/2D-PAGE separation and MALDI-MS/MS, we identified several angiogenesis inhibitors that were upregulated and pro-angiogenic factors that were downregulated after ZOL treatment. Functional studies demonstrate the improved efficacy of ZOL on MDA-231BO compared to MDA-MB-231 controls. Taken together, these results further support a model that ZOL tips the ‘angiogenic switch’ in favor of anti-angiogenic factors in cancer cells with a propensity for bone metastases. Partial research support came from NIH 5P20MD002732
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 4261. doi:10.1158/1538-7445.AM2011-4261
Abstract 4266: Acquired resistance to sorafenib yields CXCL12 (SDF1α) over-expression and increases invasion in hepatocarcinoma cells
Authors: Riveiro Maria E. , Serova Maria , Huet Guillemette , Dumont Patrick , Dokmak Safi , Albert Sébastien , Bieche Ivan , Raymond Eric , Faivre Sandrine 
Published: July 2012

Abstract
Background: Sorafenib has a well known efficacy in patients with advanced hepatocellular carcinoma (HCC). Sorafenib displays antiangiogenic effects by targeting receptors for VEGF (VEGFR2 and VEGFR3) and PDGF (PDGFRβ) and blocks cancer cell proliferation by targeting RAF/MEK/ERK signalling. However, disease-stabilizing effects are eventually followed by emergence of resistance in patients. The aim of the present work was to describe mechanisms associated with acquired resistance to sorafenib.
Materials and Methods: Cell proliferation and clonogenic survival were evaluated in sorafenib-sensitive and -resistant HCC models. Invasiveness of cells was determined by Matrigel invasion assay. qRT-PCR and western blot assays were used to assess a panel of genes and proteins. In vivo sorafenib efficacy was determined in SCID mice bearing SK-HEP1 xenografts. The drug was administered orally, once daily at dose levels of 10 and 30 mg/kg until sorafenib-resistance appearance, starting when tumors were detectable (100-300mm3).
Results: The SK-sora cell line was established from the parental SK-HEP1 cell line using a stepwise exposure to increasing sorafenib concentrations for more than 6 months. Exposure to 48-hour sorafenib led to IC50s of 8.3 and 15.9 µM in SK-HEP1 and SK-sora cells, respectively. Clonogenic assay also indicated a significant sorafenib resistance in SK-sora cells. Sorafenib-resistant cells did not display cross-resistance to sunitinib, another multitarget inhibitor. In addition, 30 days sorafenib withdrawal did not restore the sensitive to the drug in Sk-sora cells. Protracted exposure to sorafenib led to a 3-fold increase mRNA expression of VEGFA, VEGFD, erbb4, IGFR1, CXCL12 (SDF-1α) and MIF in SK-sora respect to parental SK-HEP1 cells. In addition we observed a basal up regulation of MAPK and AKT survival signalling pathways as measured by p-ERK1/2, p-AKT and p-S6rp levels in SK-sora cells. Matrigel assay revealed a 3 fold (p&lt;0.05) increase in the number of invasive SK-sora cells respect to SK-HEP1 cells. Current in vivo studies point out that sorafenib (30 mg/kg/day) significantly suppressed SK-HEP1 xenograft tumor growth (34.6%; p&lt;0.05) after 25 days of treatment. Mechanisms associated with resistance to sorafenib in mice will be explored.
Conclusions: Our data show that acquired resistance to sorafenib is associated with the activation of the AKT and MAPKs pathways together with an increased invasion in HCC cells. The role of CXCR4/CXCL12 axis in this model will be explored.
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 4266. doi:10.1158/1538-7445.AM2011-4266