tbuckley/cabot-search huggingface dataset:
Abstract 1681: Inhibition of tumor growth in vivo through neutralization of the interaction of MCAM with laminin alpha 4
Authors: Ken Flanagan, Lauri W. Li, Carlos Lorenzana, Stephen J. Tam, Yue Liu, Philip J. Dolan, Lana Alexander, Josh Salmans, Robin M. Barbour, Jeffrey N. Higaki, Tarlochan Nijjar, Wagner Zago, Ted A. Yednock, Gene Kinney
Journal: Cancer Research (2015)

Abstract Melanoma cell adhesion molecule (MCAM/CD146) is highly expressed on a subset of many tumor types including melanoma and glioblastoma, and expression of MCAM correlates with enhanced cellular invasion, increased metastasis, and poor patient prognosis. The expression of MCAM on tumor cells confers unique migratory and adhesion capacity, which, if specifically targeted, could result in interruption of multiple biological processes required for tumor growth and spread. Although a role for MCAM in tumor progression has long been appreciated, the unidentified ligand for MCAM precluded the development of targeted approaches to inhibit extracellular interactions mediated by MCAM. Recently, we identified the MCAM ligand as laminin alpha 4. Laminin alpha 4 is present within the extracellular matrix of the tumor in addition to the vasculature throughout the body, providing an adhesive substrate for MCAM expressing tumor cells both within the tumor microenvironment and the blood vessels. The presence of laminin alpha 4 within the tumor and the vasculature may allow for a biological interaction by which MCAM mediated adhesion could be involved in both the homotypic aggregation required for tumor growth, in addition to the vascular adhesion required for the processes of metastasis and angiotropism. We generated monoclonal antibodies that bind to the epitope required for MCAM interactions with laminin alpha 4. Such antibodies entirely abrogate interactions of the tumor cell with laminin alpha 4 in vitro. Furthermore, we characterized the inhibition of tumor growth in vivo mediated by neutralization of MCAM/laminin alpha 4 interactions. Notably, tumor growth was delayed by blockade of MCAM, but required inhibition of both the MCAM expressed by the tumor, as well as vascular MCAM. We further characterize the unique pattern of MCAM expression on tumor cells within the perivascular extracellular matrix in human tumors, which suggest that these interactions are involved in human disease pathogenesis. Thus, antibodies neutralizing the interaction between MCAM and laminin alpha 4 have potential to inhibit a critical molecular interaction used by myriad tumor types. Citation Format: Ken Flanagan, Lauri W. Li, Carlos Lorenzana, Stephen J. Tam, Yue Liu, Philip J. Dolan, Lana Alexander, Josh Salmans, Robin M. Barbour, Jeffrey N. Higaki, Tarlochan Nijjar, Wagner Zago, Ted A. Yednock, Gene Kinney. Inhibition of tumor growth in vivo through neutralization of the interaction of MCAM with laminin alpha 4. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1681. doi:10.1158/1538-7445.AM2015-1681
Inversely to DNMT3A, IDH1/IDH2 Are Good Targets for Monitoring Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML): A Pilot Study of the ALFA Group
Authors: Houria Debarri, Delphine Lebon, Christophe Roumier, Meyling Cheok, Alice Marceau-Renaut, Olivier Nibourel, Sandrine Geffroy, Nathalie Helevaut, Philippe Rousselot, Jean-Pierre Marolleau, Claude Gardin, Denis Caillot, Martin Figeac, Céline Berthon, Bruno Quesnel, Nicolas Boissel, Sylvie Castaigne, Hervé Dombret, Aline Renneville, Claude Preudhomme
Journal: Blood (2014)
Abstract 5048: The cholesterol metabolite, 27-hydroxycholesterol stimulates cell proliferation in prostate epithelial cell lines via estrogen receptor beta
Authors: Shaneabbas Raza, Jared Schommer, Megan Meyer, Bin Guo, Kimberly Hammer, Othman Ghribi
Journal: Cancer Research (2015)

Abstract For every 6 men, 1 will be diagnosed with prostate cancer (PCa). Estrogen receptors are known to play a role in prostate carcinogenesis however, it is unclear whether the estrogenic effects are estrogen receptor α (ERα) or estrogen receptor β (ERβ) mediated. Although, it is speculated that ERα is associated with harmful effects on PCa while ERβ plays a more protective role on PCa, clinical trials using ERβ selective modulators have not shown improved clinical outcomes. Hence, the role of ERβ in PCa is yet to be understood. Recently a cholesterol oxidized metabolite (oxysterol), 27- hydroxycholesterol (27-OHC), was found to bind to both estrogen receptors (ERs) and act as a selective ER modulator (SERM). 27-OHC is the most prevalent cholesterol metabolite present in the blood with levels increasing with oxidative stress and age, especially in men. Increased 27-OHC levels are also found in individuals with hypercholesterolemia, which is also a risk factor for PCa. The role of 27-OHC through its action on estrogen receptors in the context of PCa is yet to be determined. We hypothesize that 27-OHC through ER activation has deleterious effect in PCa. We found that incubation with 27-OHC of RWPE-1, LNCaP and PC3 cells increased cell proliferation significantly. Using the ER inhibitor, Fulvestrant, we demonstrate that upon co-treatment with 27-OHC and fulvestrant, cell proliferation is reduced to basal levels, indicating the involvement of ERs. Interestingly, levels of ERβ, and to a lesser extent ERα, were increased following incubation of RWPE-1, LNCaP and PC3 with 27-OHC. Furthermore, in the presence of the ERβ specific inhibitor, PHTPP, we show that 27-OHC- induced proliferation is attenuated. Unexpectedly, while 27-OHC increases cell invasion in the moderately metastatic LNCaP, it decreases cell invasion in normal cells, RWPE-1 and highly metastatic, PC3. Altogether, our results propose dysregulated levels of 27-OHC as a new risk factor for prostate cancers with low metastatic potential. This indicates a novel role for 27-OHC in the etiopathogenesis of in PCa. Note: This abstract was not presented at the meeting. Citation Format: Shaneabbas Raza, Jared Schommer, Megan Meyer, Bin Guo, Kimberly Hammer, Othman Ghribi. The cholesterol metabolite, 27-hydroxycholesterol stimulates cell proliferation in prostate epithelial cell lines via estrogen receptor beta. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5048. doi:10.1158/1538-7445.AM2015-5048
Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab
Authors: Yasmin Abaza, Hagop Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O’Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
Journal: Blood (2016)
Abstract 4645: Decursin, a coumarin compound, inhibits the growth of human hepatoma cells involving cell cycle arrest, apoptosis, and autophagy
Authors: Praveen K. Kujur, Dongsool Yim, Rana P. Singh
Journal: Cancer Research (2015)

Abstract Although recent advances have been made for the treatment of liver cancer, it still remains the sixth most diagnosed cancer worldwide and second most cause of mortality related to cancer. Decursin, a naturally occurring coumarin compound isolated from Angelica gigas Nakai is known for its hepatoprotective activity. For the first time we show that decursin has strong cytotoxic and growth inhibitory effects against liver cancer cells. Decursin (1-25 μM) resulted in a dose-dependent inhibition of Hep3B cell proliferation by upto 65-85% (p&amp;lt;0.005-0.001) in 24-48 h. Similarly in HepG2 cells, decursin (25-100 μM) decreased cell number by upto 61-74% (p&amp;lt;0.005-0.001) at 24-48 h. Growth inhibition was not due to the cell death in HepG2 cells, whereas, Hep3B cells showed an increased cell death (9-45%; p&amp;lt;0.001). Decursin enhanced sub-G1 population of cells in Hep3B but not in HepG2. Further, decursin induced G1 arrest at lower doses, however, at the higher doses cell death prevailed over cell cycle arrest. A consistent G2/M phase arrest in HepG2 cells at all the time points, however, at 100 μM, there was an induction of S-phase arrest. Decursin strongly decreased the colony forming efficiency of Hep3B cells. Decursin induced both apoptotic and autophagic cell death. In flow cytometry analyses, an increase in the acidic vesicular organelle development was observed at 24 and 48 h in Hep3B cells. Interestingly, in decursin treated HepG2 cells, autophagic induction occurred much later (48 h). This was further validated by MDC staining. Mechanistic studies for cell cycle regulators showed that decursin mediated G1 arrest could be via an increase in p21/cip1. Concomitantly, we observed reduced levels of Cyclin A and B1 and their respective kinases. PCNA, a marker of proliferation showed decreased in expression. Decursin mediated induction of apoptosis involved cleavage of caspase-3 and PARP and reduction in survivin level. This was accompanied by an enhanced Bax/Bcl-2 ratio. Additionally, a potent decrease in the phosphorylation of IGF-IR and its downstream effector Akt, was observed. Decursin increased Erk1/2 phosphorylation, however, it was not associated with cell growth or survival. Collectively, these findings suggest that decursin strongly inhibits liver cancer growth and proliferation involving induction of cell cycle arrest, apoptosis and autophagy and could be further explored and developed as novel treatment option for the hepatic malignancies. Citation Format: Praveen K. Kujur, Dongsool Yim, Rana P. Singh. Decursin, a coumarin compound, inhibits the growth of human hepatoma cells involving cell cycle arrest, apoptosis, and autophagy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4645. doi:10.1158/1538-7445.AM2015-4645
Treatment Outcomes and Prognostic Factors of Ifosfamide, Etoposide, Cytarabine, Methotrexate, and Dexamethasone (IVAMdex) Regimen As 3rd Line (2nd salvage) Chemotherapy in Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma
Authors: Yong Park, Seh Jong Park, Seok Young Lee, Se Ryeon Lee, Hwa Jung Sung, Seok Jin Kim, Chul Won Choi, Byung Soo Kim
Journal: Blood (2011)
Abstract 1145: The TDP-43 confers resistance to metabolic stress condition via activating autophagy in GBM cells
Authors: Tzu-Wei Lin, Chen-Wen Wu
Journal: Cancer Research (2015)

Abstract Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. TDP-43 (TARDBP), a DNA and RNA binding protein, is well known to play a key role in RNA processing, including involving in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recent reports suggested that TDP-43 participate to the regulation of metabolic glycolysis in cancer. Overcoming metabolic stress is critical for cancer cell survival and growth in nutrient deprivation condition. Herein we found protein level of TDP-43 was increased in nutrient deprivation. Overexpression TDP-43 promotes glioblastoma cell survival and suppressed the activated-form levels of caspase 3 protein under nutrient deprivation. Overexpression of TDP-43 increased the tumorigenicity as determined by anchorage-independent growth assay and xenografts in immunocompromised mice model. Under nutrient deprivation, we also found that TDP-43-overexpression induced autophagy. Recent evidence suggests that autophagy is a cell survival mechanism in cancer cells. Finally, treatment of autophagy inhibitor blocks the survival of TDP-43 overexpressing GBM cells in nutrient deprivation condition. By this study, we presume TDP-43 enhanced GBM cells tumorigincity, activated autophagy and inhibited cell death under nutrient deprivation condition. TDP-43 is potentially the new aspects for understanding the tumorigenicity and metablolic regulation for malignant brain tumors and GBM. Citation Format: Tzu-Wei Lin, Chen-Wen Wu. The TDP-43 confers resistance to metabolic stress condition via activating autophagy in GBM cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1145. doi:10.1158/1538-7445.AM2015-1145
Abstract 3713: Second malignant neoplasms after non-CNS embryonal tumors in North America
Authors: Xuchen Zong, Jason D. Pole, Paul Grundy, Salaheddin M. Mahmud, Louise Parker, Rayjean J. Hung
Journal: Cancer Research (2015)

Abstract Background: Childhood cancer survivors are known to face an increased risk of adverse medical conditions related to the initial disease or cancer treatment; however, few studies have quantified the risk of second malignant neoplasms (SMNs) among survivors of childhood non-CNS embryonal cancer due to its rarity. In this study, we combined data from the U.S. and Canada to investigate the risk of SMNs. Methods: Data from 13,107 survivors of childhood non-CNS embryonal tumors reported to the Surveillance Epidemiology and End Results (SEER) program in the U.S. and 8 population-based cancer registries in Canada (between 1973 to 2010) were analyzed. We calculated standardized incidence ratios (SIRs) for all types of second primaries by type of first primary, age at first cancer diagnosis, and follow-up duration. Expected numbers of SMNs were obtained by applying age-, sex-, calendar year-, and registry-specific cancer incidence rates to person-years contributed by these cancer survivors. Results: One hundred and ninety SMNs were reported over 134,548 person-years of follow-up, with bone and joint cancer and leukemia being the most common SMNs (19% and 16% respectively). The SIR for all SMNs combined was 6.4 (95% CI: 5.53-7.35). Most site-specific SIRs were significantly increased, ranging from 36.4 (95% CI: 25.5-49.2) for bone and joint cancer, to 3.1 (95% CI: 1.54-5.2) for brain tumor. Among all the survivors, those who survived rhabdomyosarcoma carried the greatest risk of SMN development with SIR of 11.5 (95% CI: 8.7-14.6). Bone and joint tumors were mostly seen among retinoblastoma survivors, reflecting a markedly risk of 139.3 (95% CI: 85-207). When stratified by follow-up period, we observed that the risk patterns varied by SMN site. For example, the risk for a second malignancy in the thyroid remained significantly increased even after 20 years of follow-up, whereas the elevated risk of secondary leukemia persisted for 10 years but decreased rapidly afterwards. Details of stratified analyses by first primary tumor site, age at first diagnosis, and follow-up duration will be presented. Conclusion: Survivors of childhood non-CNS embryonal tumors have increased risks of developing SMNs compared to the general population. Increased surveillance may explain the elevated risks within the first few years of the initial diagnosis, but treatment effects and shared etiology most likely account for the excess risk later in life. Citation Format: Xuchen Zong, Jason D. Pole, Paul Grundy, Salaheddin M. Mahmud, Louise Parker, Rayjean J. Hung. Second malignant neoplasms after non-CNS embryonal tumors in North America. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3713. doi:10.1158/1538-7445.AM2015-3713
Prospective randomized controlled study on the effects of <i>Saccharomyces boulardii</i> CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers
Authors: Toufic A. Kabbani, Kumar Pallav, Scot E. Dowd, Javier Villafuerte-Galvez, Rohini R. Vanga, Natalia E. Castillo, Joshua Hansen, Melinda Dennis, Daniel A. Leffler, Ciarán P. Kelly
Journal: Gut Microbes (2016)

Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis. This study aimed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms of healthy humans.Healthy subjects were randomized to one of 4 study groups: SB for 14 days, AC for 7 days, SB plus AC, Control (no treatment). Participants gave stool samples and completed gastro-intestinal symptom questionnaires. Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing (bTEFAP).Only one subject withdrew prematurely due to adverse events. Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone. Control subjects had a stable microbiota throughout the study period. Significant microbiota changes were noted in the AC alone group during antibiotic treatment. AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter. Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotherapy. No significant shifts in bacterial genera were noted in the SB alone group. Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores.Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera. S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea.
Immunohistochemical profiles of normal and tumor breast from BRCA1 carriers and matched sporadic controls: Clues for chemoprevention
Authors: V. Suciu, M. C. Mathieu, I. Kloos, R. Rouzier, V. Vélasco, J. C. Sabourin, B. Bressac -De Paillerets, A. Chompret, S. Delaloge
Journal: Journal of Clinical Oncology (2004)

9686 Background: Alternatives to surgical prophylaxis are hardly needed in women with a hereditary risk of breast cancer. The aim of this study was to screen BRCA1-related and sporadic breast tumors and non-tumor distant breast tissues for alterations susceptible to be targets for chemoprevention. Methods: 25 breast samples of BRCA1 mutation carriers and carefully matched sporadic controls were selected from the tumor bank of our institution. Tumor samples were screened using a tissue array, and normal and intermediate tissues from the same individuals by standard immunohistochemistry (IHC). Results: Both groups were comparable regarding the matching criteria: age (med 39 and 41), tumor size (med 23 and 22 mm), SBR grade (grade 3: 76 and 71%), histological type. In tumors, p53 over expression and high Ki67 expression rates did not differ between both groups, while PR (12 vs 38%, p=0.03) and, to a lesser extent, ER (p=0.08) were less often expressed in BRCA1-related tissues than in controls. In normal tissues, ER was significantly more often expressed (78 vs 45%, p=0.02) and Cox 2 over expression tended to occur more frequently in BRCA1-related samples (48%) than in controls (23%, p=0.07). Cox2 expression tended to be correlated with ER and PR negativity in BRCA1-related and control breast tumors, and the opposite in normal breast samples. Her2 and EGF-R expression did not differ significantly between both groups. 17% of normal BRCA1-related but none of the control normal breast tissues over expressed p53. Proliferative benign breast lesions were rare, as many in both groups. ER and Cox2 were expressed in most benign lesions in BRCA1 carriers as well as controls. Conclusions: Both the tumor and normal breast IHC profiles differ between BRCA1 mutation carriers and sporadic patients. The loss of ER expression is not an early event in BRCA1-related breast carcinogenesis. Cox2 is over expressed early in BRCA1 tissues independently of ER and PR expression, and may be a target for chemoprevention in this population. No significant financial relationships to disclose.
Abstract 4486: Antiangiogenic platinum through glycan targeting
Authors: Erica J. Peterson, Susan J. Berners-Price, Anna Bezos, Lisa Bohlman, Samantha J. Katner, A. Gerard Daniel, Chih-Wei Chang, Mark von Itzstein, Christopher R. Parish, Nicholas P. Farrell
Journal: Cancer Research (2015)

Abstract Heparanase is an endo-β-D-glucuronidase that cleaves heparan sulfate glycosaminoglycans (HS-GAGs) in the extracellular matrix and basement membrane. Cancer cells that aberrantly express heparanase potentiate tumor progression, invasion and metastasis in two distinct ways; (1) cleavage of HS-GAGs releases growth-factors to directly activate growth receptors and (2) degradation of the heparan sulfate structural component of the extracellular matrix (ECM) allows metastatic spread of cancer cells. Recently, we determined that accumulation and cytotoxicity of polynuclear platinum compounds (PPCs), including the Phase II clinical trial compound, BBR3464 (+4), are dependent on the presence of cell-surface GAGs. Here, we demonstrate that high affinity PPC-GAG binding provides a new approach to glycan-based targeting by protection against enzymatic cleavage by heparanase. It was determined by NMR spectroscopy, that PPCs, especially the higher charged compound, TriplatinNC (+8), inhibit heparanase cleavage of the oligosaccharide, Fondaparineaux. Further, using the human umbilical primary cell line, HUVEC, it was determined that PPCs reduce heparanase cleavage of the GAG-bound growth factor, bFGF, from ECM. The end result of inhibition of heparanase cleavage is a reduction in tumor invasion and angiogenesis. Using the matrigel invasion assay, we show that sub-cytotoxic doses of PPCs, but not cisplatin, reduces serum-induced invasion of HCT116 cells through basement membrane. In an ex vivo rat aorta model, PPCs exhibit antiangiogenesis activity, measured by the inhibition of new blood vessel growth sprouting from the original aortic ring. Together, these encouraging results support the potential to combine anti-metastatic and cytotoxic activity in the development of dual-function platinum-based drugs. Citation Format: Erica J. Peterson, Susan J. Berners-Price, Anna Bezos, Lisa Bohlman, Samantha J. Katner, A. Gerard Daniel, Chih-Wei Chang, Mark von Itzstein, Christopher R. Parish, Nicholas P. Farrell. Antiangiogenic platinum through glycan targeting. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4486. doi:10.1158/1538-7445.AM2015-4486
Prophylactic oral calcium supplementation therapy to prevent early post thyroidectomy hypocalcemia and evaluation of postoperative parathyroid hormone levels to detect hypocalcemia: A prospective randomized study
Authors: Ilker Murat Arer, Murat Kus, Nezih Akkapulu, Huseyin Ozgur Aytac, Hakan Yabanoglu, Kenan Caliskan, Mehmet Akin Tarim
Journal: International Journal of Surgery (2016)