tbuckley/cabot-search huggingface dataset:
The novel anti-cancer agent curcumin induces cytotoxicity in pancreatic cancer cell lines in vitro
Authors: Rosemary Fryer, Marie-Christine LaBarthe, Angus Dalgleish, Christine Galustian
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5673 

Pancreatic adenocarcinoma is the fifth leading cause of death from cancer. This cancer is responsible for a death rate which almost equals the incidence rate. Presently, patients can expect a very poor 12-month survival rate of approximately 10%, dropping to 3% for 5-year survival rate post-treatment. In light of this, novel anti-cancer therapeutics are now being investigated. One novel drug of particular interest is the plant derivative curcumin from Curcuma longa . As an initial investigation into the anti-tumour effects of curcumin against the pancreatic cancer cell lines PANC-1, MIA-PaCa-2 and Colo357, we employed the MTT cytotoxicity and [3H]-thymidine proliferation assays to establish if cytotoxicity was induced after incubation with increasing concentration of drug (0.75-250μM) over 16, 24 and 48 hours at 37oC. Cell death due to curcumin exposure was found to increase in both a dose and time-dependent manner in all cell lines. In contrast, no cytotoxic effects were seen with normal cells such as peripheral blood mononuclear cells. Following this, we used AnnexinV/PI staining and flow cytometry to study if cell death due to curcumin was via necrosis or apoptosis. Apoptosis was found to occur and increase with increasing concentration of curcumin. In both assays and with all cell lines, curcumin was found to be up to 200 times more effective than gemcitabine according to IC50 data obtained from proliferation assays. To continue the study of this agent, we have done an initial microarray analysis on Colo357 cells to discover which genes are up- and down-regulated by short-term, low dose curcumin exposure (5μM, 4h incubation at 37oC). Among genes that were upregulated were genes relating to tumour suppression such as SMAD4, involved in modulation of TGFβ and Wnt signaling, and genes relating to increased anti-tumour immune response such as CD1d, the ligand for NKT cells. Also there was downregulation of immunomodulatory genes such as HLA-G, which provide a possible escape from immunosurveillance. Currently we are looking at the ability of curcumin to halt invasion of pancreatic cancer cells using an in vitro Matrigel invasion assay. We are also investigating possible synergy of this drug with other novel and existing chemotherapeutics. Further work will include RT-PCR and Western blot to support Microarray results.
The role of autophagy in the cross-talk between epithelial-mesenchymal transitioned tumor cells and cancer stem-like cells
Authors: Fabrizio Marcucci, Pietro Ghezzi, Cristiano Rumio
Journal: Molecular Cancer (2017)

Epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC) are becoming highly relevant targets in anticancer drug discovery. A large body of evidence suggests that epithelial-mesenchymal transitioned tumor cells (EMT tumor cells) and CSCs have similar functions. There is also an overlap regarding the stimuli that can induce the generation of EMT tumor cells and CSCs. Moreover, direct evidence has been brought that EMT can give rise to CSCs. It is unclear however, whether EMT tumor cells should be considered CSCs or if they have to undergo further changes. In this article we summarize available evidence suggesting that, indeed, additional programs must be engaged and we propose that macroautophagy (hereafter, autophagy) represents a key trait distinguishing CSCs from EMT tumor cells. Thus, CSCs have often been reported to be in an autophagic state and blockade of autophagy inhibits CSCs. On the other hand, there is ample evidence showing that EMT and autophagy are distinct events. CSCs, however, represent, by themselves, a heterogeneous population. Thus, CSCs have been distinguished in predominantly non-cycling and cycling CSCs, the latter representing CSCs that self-renew and replenish the pool of differentiated tumor cells. We now suggest that the non-cycling CSC subpopulation is in an autophagic state. We propose also two models to explain the relationship between EMT tumor cells and these two major CSC subpopulations: a branching model in which EMT tumor cells can give rise to cycling or non-cycling CSCs, respectively, and a hierarchical model in which EMT tumor cells are first induced to become autophagic CSCs and, subsequently, cycling CSCs. Finally, we address the therapeutic consequences of these insights.
Cardiac Toxicity Associated with the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin) in Combination with CHOP (A-CHOP) Chemotherapy for Peripheral T Cell Lymphoma (PTCL): The ECOG 2404 Trial.
Authors: Ranjana H Advani, Fangxin Hong, Kristen N. Ganjoo, Judith B. Manola, Lode J. Swinnen, Thomas M Habermann, Sandra J Horning
Journal: Blood (2009)
MORAb-003 inhibits folate-driven growth mediated by the human folate receptor alpha
Authors: E. Routhier, H. Turchin, R. Patel, W. Ebel, P. Sass, N. Nicolaides, L. Grasso
Journal: Journal of Clinical Oncology (2006)

10108 Background: MORAb-003 is a therapeutic humanized antibody currently in Phase I clinical trials for advanced ovarian cancer, and is directed against the human folate receptor alpha (FRα), an antigen which is highly overexpressed on the surface of the majority of ovarian cancers. Overexpression of FRα has been shown to confer a growth advantage to tumorigenic cells in vitro, under conditions of reduced folate availability. We have previously determined that MORAb-003 elicits robust antibody-dependent cellular cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC) in vitro, and is effective in mouse xenograft models of human ovarian cancer. We now show that MORAb-003 possesses novel, growth-inhibitory functions distinct from its immune effector properties. This activity can be recapitulated, using a cell-based assay to score inhibition of folate-dependent growth. Methods: Chinese Hamster Ovary (CHO) cells were engineered to express surface FRα. The cells were cultured under a low folate (&lt; 20 nM) regimen, then re-fed medium supplemented with various concentrations (0–10 μM) of 5-methyltetrahydrofolate (5-MTF), a folate preferentially internalized by the FRα. Cellular proliferation was measured as a function of added 5-MTF, in the presence or absence of MORAb-003. Results: FRα-expressing CHO cells were found to require approximately 100-fold lower 5-MTF than a matched, non-expressing cell line. This increased proliferation could be reduced in a concentration-dependent manner by MORAb-003. Conclusions: MORAb-003 can antagonize the activity of human FRα, resulting in the loss of growth advantage conferred by overexpression of FRα under conditions which bracket physiological (10–100 nM) folate concentrations. [Table: see text]
Exemestane (E) vs tamoxifen (T) as neoadjuvant endocrine therapy for postmenopausal women with ER+ breast cancer (T2N1–2, T3N0–1, T4N0M0)
Authors: V. Semiglazov, A. Kletsel, V. Semiglazov, E. Zhiltzova, V. Ivanov, G. Dashyan, A. Bozhok, O. Melnikova, R. Paltuev, L. Berstein
Journal: Journal of Clinical Oncology (2005)

530 Background: There is considerable evidence that aromatase inhibitors are superior to T as first line endocrine therapy for metastatic disease. E an aromatase inactivator, is effective in women whose tumor has progressed despite T therapy. Methods: 151 PM women with ER+ breast cancer (BC) were randomly assigned once-daily treatment with either E alone 25 mg (n=76), or T alone (n=75) for 3 months. The primary endpoint was clinical objective response (OR). Secondary endpoints were OR determined by mammography and ultrasound, and number of pts who underwent breast conserving surgery (BCS). Result: Clinical, mammography, BCS rate are shown in the table. A pathological CR was shown in two pts in the E group and 2 pts in the T group. Response to any type of endocrine treatment was more likely in pts with higher levels of ER expression. Median time to response was 57 days in the E group and 70 days in the T group (p<0.05). All pts with disease progression after endocrine treatment were recommended to receive chemotherapy AT (doxorubicine 60 mg/m2 + paclitaxel 200 mg/m2, every 3 weeks to 4 cycles). Clinical OR after chemotherapy (second line neoadjuvant treatment) was 59.6%. During 50 months of follow up local recurrences were detected in 5.2% pts of E group and 8% pts in T group (p>0.05). 3-year disease free survival rates were 78.9% in E group and 74.6% in T group (p>0.05). Conclusion: E is more effective than T as neoadjuvant therapy for PM pts with ER+ tumors in rate of clinical OR and BCS. No significant financial relationships to disclose.
Arsenic Trioxide Plus ABT-737 Is Synergistic to Induce Apoptosis in AML Cells by Repression of Mcl-1 Protein and Inactivation of Bcl-2 Protein
Authors: Lijuan Xia, Rui Wang, Hao Qian, Janice Gabrilove, Samuel Waxman, Yongkui Jing
Journal: Blood (2008)
China's Health Reform Update
Authors: Gordon G. Liu, Samantha A. Vortherms, Xuezhi Hong
Journal: Annual Review of Public Health (2017)

China experienced both economic and epistemological transitions within the past few decades, greatly increasing demand for accessible and affordable health care. These shifts put significant pressure on the existing outdated, highly centralized bureaucratic system. Adjusting to growing demands, the government has pursued a new round of health reforms since the late 2000s; the main goals are to reform health care financing, essential drug policies, and public hospitals. Health care financing reform led to universal basic medical insurance, whereas the public hospital reform required more complex measures ranging from changes in regulatory, operational, and service delivery settings to personnel management. This article reviews these major policy changes and the literature-based evidence of the effects of reforms on cost, access, and quality of care. It then highlights the outlook for future reforms. We argue that a better understanding of the unintended consequences of reform policies and of how practitioners' and patients' interests can be better aligned is essential for reforms to succeed.
Impact of Cytogenetic Abnormalities and Cytogenetic Response to Hypomethylating Agents (HMAs) in Patients (pts) with Lower Risk Myelodysplastic Syndromes (MDS)
Authors: Guillermo Montalban-Bravo, Guillermo Garcia-Manero, Nicholas J. Short, Koji Sasaki, Mikkael A. Sekeres, Rami S. Komrokji, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Tapan Kadia, Gautam Borthakur, Courtney DiNardo, Darla Miller, Zeev Estrov, Naveen Pemmaraju, Naval Daver, Marina Konopleva, Jorge E. Cortes, Hagop M. Kantarjian, Elias Jabbour
Journal: Blood (2015)
Differential Responsiveness of HSPCs Harvested From Bone Marrow (BM), Mobilized Peripheral Blood (mPB) and Umbilical Cord Blood (UCB) to the BM Homing Factors Stromal-Derived Factor-1 (SDF-1), Sphingosine-1 Phosphate (S1P) and Ceramide-1 Phosphate (C1P) Is Related to the Desensitization of mPB and UCB HSPCs by S1P and C1P Present in mPB and UCB Plasma
Authors: Ahmed Abdel-Latif, Anush V Karapetyan, Chihwa Kim, Mariusz Z Ratajczak
Journal: Blood (2011)
Feasibility and Outcome of Sequential Therapy in the Setting of HLA-Haploidentical Transplantation Utilizing Reduced-Intensity Conditioning, T-Cell-Replete Grafts and Post-Transplantation High-Dose Cyclophosphamide in the Treatment of High-Risk AML and MDS
Authors: Dusan Prevalsek, Susanne Fritsch, Max Hubmann, Nicole Engel, Anna-Katharina Zoellner, Thomas Köhnke, Veit Leonhard Bücklein, Christoph Schulz, Friederike Mumm, Christina Theresa Rieger, Georg Ledderose, Hans-Joachim Stemmler, Karsten Spiekermann, Wolfgang Hiddemann, Andreas Hausmann, Johanna Tischer
Journal: Blood (2015)
Oligonucleotide Microarray Analysis of Gene Expression Profiles in Chronic Graft-Versus-Host Disease (GVHD) after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Sukjoong Oh, Young Ju Lee, Soo Mee Kwon, Eunkyung Park, Sungbum Cho, In Ho Kim, Sung Soo Yoon, Joo Han Kim, Seonyang Park
Journal: Blood (2006)
ARL-IPI - A New Prognostic Score for AIDS-Related Lymphomas in the Rituximab Era
Authors: Stefan K Barta, Xiaonan Xue, Dan Wang, Jeannette Y Lee, Lawrence D. Kaplan, Josep-Maria Ribera, Albert Oriol, Olga Garcia, Mireia Morgades, Michele Spina, Umberto Tirelli, Francois Boue, Wyndham H. Wilson, Christoph Wyen, Kieron Dunleavy, Joseph A Sparano
Journal: Blood (2012)
Phase I/II Study of MGCD0103, an Oral Isotype-Selective Histone Deacetylase (HDAC) Inhibitor, in Combination with 5-Azacitidine in Higher-Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML).
Authors: Guillermo Garcia-Manero, Allen S. Yang, Virginia Klimek, Jorge Cortes, Farhad Ravandi, Willie M. Newsome, Julie Dumouchel, Marja Dubay, Zoumei Li, Christiane Maroun, Eric Laille, Hagop Kantarjian, Robert E. Martell, Selina Luger
Journal: Blood (2007)
Targeting acute myeloid leukemia stem cell signaling by natural products
Authors: Kodappully Sivaraman Siveen, Shahab Uddin, Ramzi M. Mohammad
Journal: Molecular Cancer (2017)

Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in adults (25%) and comprises 15-20% in children. It is a genetically heterogeneous aggressive disease characterized by the accumulation of somatically acquired genetic changes, altering self-renewal, proliferation, and differentiation of hematopoietic progenitor cells, resulting in uncontrolled clonal proliferation of malignant progenitor myeloid cells in the bone marrow, peripheral blood, and occasionally in other body tissues. Treatment with modern chemotherapy regimen (cytarabine and daunorubicin) usually achieves high remission rates, still majority of patients are found to relapse, resulting in only 40-45% overall 5 year survival in young patients and less than 10% in the elderly AML patients. The leukemia stem cells (LSCs) are characterized by their unlimited self-renewal, repopulating potential and long residence in a quiescent state of G0/G1 phase. LSCs are considered to have a pivotal role in the relapse and refractory of AML. Therefore, new therapeutic strategies to target LSCs with limited toxicity towards the normal hematopoietic population is critical for the ultimate curing of AML. Ongoing research works with natural products like parthenolide (a natural plant extract derived compound) and its derivatives, that have the ability to target multiple pathways that regulate the self-renewal, growth and survival of LSCs point to ways for a possible complete remission in AML. In this review article, we will update and discuss various natural products that can target LSCs in AML.
Impact of Genetic Abnormalities After Allogeneic Stem Cell Transplantation in Multiple Myeloma: Report of the Societe Francaise De Greffe De Moelle Et De Therapie Cellulaire.
Authors: Damien Roos-Weil, Philippe Moreau, Herve Avet Loiseau, Mathieu Kuentz, Noel-Jean Milpied, Jean Louis Golmard, Gerard Socié, Sabine Furst, Anne Huynh, Stephane Vigouroux, Steven Le Gouill, Anne Thiebaut, Agnes Buzyn, Jean-Yves Cahn, Natacha Maillard, Ibrahim Yakoub-Agha, Jean Soulier, Nicole Raus, Jean-Paul Fermand, Bernard Rio, Michel Attal, Mauricette Michallet, Didier Blaise, Nathalie Dhedin
Journal: Blood (2009)
Low or Undetectable Numbers of Philadelphia Chromosome Positive (Ph+) Leukemia Cells in the Primitive (CD34posCD38neg) Stem Cell Fraction in Chronic Myeloid Leukemia (CML) Patients during Tyrosine Kinase Inhibitor Therapy.
Authors: Satu Mustjoki, Peter Rohon, Katrin Rapakko, Sari Hernesniemi, Perttu Koskenvesa, Tuija Lundán, Kimmo Porkka
Journal: Blood (2008)
Predictive Value of 18F-FDG PET/CT for Vascular Invasion in Patients With Hepatocellular Carcinoma Before Liver Transplantation
Authors: Chun-Yi Lin, Chiung-Wei Liao, Lu-Yen Chu, Kuo-Yang Yen, Long-Bin Jeng, Cheng-Nan Hsu, Cheng-Li Lin, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2017)

Background Positron emission tomography-computed tomography using 18F-fluorodeoxyglucose (18F-FDG PET/CT) has been widely used in oncology. Vascular invasion of hepatocellular carcinoma (HCC) is associated with a high risk of tumor recurrence and low survival rates after liver transplantation (LT). This retrospective study determined the predictive value of 18F-FDG PET/CT for vascular invasion in patients with HCC before LT. Methods Sixty-five patients with HCC who underwent 18F-FDG PET/CT before LT were retrospectively included between January 2010 and July 2012. Volumes of interest (VOIs) were drawn for the tumors and normal liver tissues, and the standardized uptake value (SUV) in each VOI was measured. The maximal SUV (SUVmax) of the tumor, the ratio of tumor SUVmax to normal liver SUVmax (TSUVmax/LSUVmax), and the ratio of tumor SUVmax to normal liver SUVmean (TSUVmax/LSUVmean) were measured. The predictive value of metabolic parameters and conventional prognostic factors were analyzed. Results Vascular invasion was pathologically confirmed in 15 (23.08%) of 65 patients. Compared with patients without vascular invasion, patients with vascular invasion exhibited significantly higher serum alpha-fetoprotein (AFP) (P < 0.001), larger tumor size (P = 0.001), higher tumor number (P = 0.017), and higher SUVmax, TSUVmax/LSUVmax ratio, and higher TSUVmax/LSUVmean ratio (P = 0.008, P = 0.002, and P = 0.006, respectively). Univariate analysis revealed that SUVmax, TSUVmax/LSUVmax ratio, and TSUVmax/LSUVmean ratio of FDG PET/CT were significantly associated with vascular invasion in patients with HCC before LT (P = 0.019, P = 0.018, and P = 0.015, respectively). Multivariate analysis revealed that the TSUVmax/LSUVmean ratio of 18F-FDG PET/CT was a significant predictor of vascular invasion (P = 0.04) and that the TSUVmax/LSUVmax ratio of 18F-FDG PET/CT was an independent predictor of vascular invasion, although this finding demonstrated borderline statistical significance (P = 0.06) in patients with HCC before LT. Conclusions According to the study results, the TSUVmax/LSUVmean ratio is an independent and significant predictor of vascular invasion, and the TSUVmax/LSUVmax ratio of 18F-FDG PET/CT is an independent predictor of vascular invasion, which is the main negative outcome after LT. Therefore, FDG PET/CT can provide vital information for determining prognosis and selecting an optimal candidate of LT for HCC.
The Effect of BIBT 986, a Novel Small Molecule Dual Inhibitor of Thrombin and Factor Xa, on Coagulation in a Model of Endotoxin Induced, Tissue Factor Triggered Coagulation Activation in Humans.
Authors: Bernd Jilma, Judith M. Leitner, Francesco Cardona, Florian B. Mayr, Christa Firbas, Karin Rathgen, Hildegard Staehle, Uwe Schuehly, Eva U. Graefe-Mody
Journal: Blood (2006)
A Phase II Study of Methotrexate (M), Vincristine (O), Pegylated L-Asparaginase (pA), and Dexamethasone (MOpAD) in Patients with Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
Authors: Tapan M. Kadia, Jorge E. Cortes, Deborah Thomas, Farhad Ravandi, Naveen Pemmaraju, Naval Daver, Alfonso Quintás-Cardama, Melanie Baccus, Rebecca Garris, Elias J. Jabbour, Hagop M. Kantarjian, Gautam Borthakur
Journal: Blood (2012)
HCP-03NEWLY DIAGNOSED SINGLE BRAIN MASS – IMPLEMENTATION AND PERFORMANCE OF A HOSPITAL-WIDE MANAGEMENT PATHWAY
Authors: Isabel Arrillaga, Aneesh Singhal, Susann Jarhult, Corey Gill, Benjamin White, SooAe Jones, Michelle Pisapia, Daniel Cahill, William Curry, Joshua Goldstein, Tracy Batchelor
Journal: Neuro-Oncology (2015)

BACKGROUND: Prior to 2012 there was no standardized admission protocol at our institution for patients presenting with a single brain mass. The service to which they were admitted, specialty consultations requested, and diagnostic testing employed varied significantly, both in the emergency department and on the inpatient services. In order to enhance management of this patient population we created and implemented a Single Brain Mass admission protocol. Our goal was to provide specialized care from a single multidisciplinary team from admission to discharge, reduce length of hospitalization, limit unnecessary diagnostic testing, and enhance patient care. METHODS: We reviewed records of 94 patients without a cancer history admitted to our emergency department with a new single brain mass between 12/2010 - 08/2014. Patients admitted prior to the protocol implementation (11/2012) were designated the pre-intervention group (PRE), and those admitted following implementation comprised the post-intervention group (POST). RESULTS: 46 patients were PRE and 48 were POST. When patients discharged to rehabilitation (35/94) were excluded from the analysis, a significantly longer mean length of stay was noted in the PRE compared to POST group (7.37 days versus 4.6 days; P= 0.01). More patients underwent CT scans of the chest, abdomen or pelvis in the PRE compared to the POST group (49% versus 17%, P = 0.001). There was no significant difference in the number of patients discharged to a rehabilitation center (38% in PRE vs. 35% in POST) or diagnosed with a brain metastasis (0.04% for both groups). Length of stay in the emergency room and time to surgery was similar across groups. CONCLUSION: Implementation of a management protocol executed by a single, specialized, multidisciplinary team streamlined the care of patients with a new single brain mass, decreased their average length of stay and reduced unnecessary diagnostic imaging tests.
Current Concepts in the Polycystic Ovary Syndrome
Authors: Andrea Dunaif, Abraham Thomas
Journal: Annual Review of Medicine (2001)

▪ Abstract Over the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in ∼50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.
Bone Marrow Immunological Changes During Treatment with Lenalidomide In Low and Intermediate-1 Risk Myelodysplastic Syndromes with Del(5Q)
Authors: Esther Natalie Oliva, Francesco Nobile, Francesca Ronco, Caterina Alati, Fortunato Morabito, Antonella Poloni, Agostino Cortelezzi, Maria Antonietta Aloe Spiriti, Alessandra Ricco, Antonio Volpe, Enrico Balleari, Grazia Sanpaolo, Massimo Breccia, Cristina Clissa, Giuliana Alimena, Roberto Latagliata
Journal: Blood (2010)
Reduced-Intensity Versus Myeloablative Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 45 Years with Acute Lymphoblastic Leukemia (ALL) in Remission: A Study From the ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT).
Authors: Junji Tanaka, Kanamori Heiwa, Nishiwaki Satoshi, Ohashi Kazuteru, Taniguchi Shuichi, Eto Tetsuya, Nakamae Hirohisa, Yoshio Katayama, Yasuo Morishima, Ritsuro Suzuki, Koji Kato, Hisashi Sakamaki, Nishimoto Naoki, Nobuo Masauzi
Journal: Blood (2012)