tbuckley/cabot-search huggingface dataset:
Mitomycin-C and capecitabine as salvage chemotherapy in pre-treated patients with advanced colorectal cancer
Authors: C. G. Gennatas, V. Michalaki, S. Gennatas, J. Kouvaris, V. Smyrniotis, J. Vasiliou
Journal: Journal of Clinical Oncology (2007)

14595 Background: To assess the activity and tolerability of the combination of Mitomycin C and Capecitabine in patients with metastatic colorectal cancer after failure of irinotecan, 5-fluorouracil (5-FU), folinic acid and oxaliplatin-containing regimens. Methods: We retrospectively reviewed 31 patients with pre-treated advanced colorectal cancer. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1000 mg/m2 twice daily on days 1–14, was initiated. Cycles were repeated every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. Results: Main patient characteristics were median age 63 years (range, 45–73); male/female ratio, 19/12. One hundred forty- six courses of therapy were given (median number, 3; range, 2–9). All patients were assessable for response, and all were assessable for toxicity. Fourteen patients had stable disease (45%). Median time to progression was 3 months (range, 1–10) and median overall survival was 8 months (range, 3–28). The regimen was very well tolerated without significant toxicity. Grade 2 toxicities were palmar-plantar erythema 6%, hematological 35%. Conclusions: Our findings suggest that the combination of Mitomycin C and Capecitabine in pre-treated patients with advanced colorectal cancer is safe and effective with an acceptable toxicity profile and a convenient administration schedule. However, further evaluation of other salvage regimens seems to be warranted. No significant financial relationships to disclose.
Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma
Authors: Esther Mena, Mehdi Taghipour, Sara Sheikhbahaei, Abhinav K. Jha, Arman Rahmim, Lilja Solnes, Rathan M. Subramaniam
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative FDG PET/CT imaging parameters for predicting patient outcomes in primary oropharyngeal squamous cell cancer (OPSCC).
More babies born to mothers with gestational diabetes have adverse outcomes, study shows
Authors: Susan Mayor
Journal: BMJ (2017)

Babies born to women who develop gestational diabetes during pregnancy have higher odds of adverse outcomes including preterm birth and larger than average size, a large scale observational study of all deliveries in France during 2012 has shown.1

The number of women developing type 2 diabetes before pregnancy or gestational diabetes during pregnancy is increasing in line with rising obesity. The adverse consequences of pregestational diabetes on offspring have been established, …
BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
Authors: Karl J. Aichberger, Matthias Mayerhofer, Maria-Theresa Krauth, Anna Vales, Sophia Derdak, Winfried F. Pickl, Christian Sillaber, Peter Valent
Journal: Blood (2005)
A phase I study evaluating DLYE5953A, an antibody-drug conjugate targeting the tumor-associated antigen lymphocyte antigen 6 complex locus E (Ly6E), in patients (Pts) with solid tumors
Authors: S. Modi, J.P. Eder, P. Lorusso, C. Weekes, S. Chandarlapaty, S.M. Tolaney, J. McLaughlin, D.R. Camidge, C.-W. Chang, D. Nazzal, S.-C. Chen, E. Schuth, F. Brunstein, W. Darbonne, W. Flanagan, A. Ungewickell, G. Shapiro
Journal: Annals of Oncology (2016)
The Prevalence of Anti-Factor VIII Antibodies in the Hemophilia A Population of the Quebec Province of Canada: Results of Testing with the Bethesda/Nijmegen Assay and with Three ELISA Assays.
Authors: Anne-Marie Vincent, David Lillicrap, Angie Tuttle, Laurence Dedeken, Christine Demers, Mariette Lépine, Jean St-Louis, Margaret Warner, Georges E. Rivard
Journal: Blood (2009)
Evidence of Polyclonal Hematopoiesis in a Large Proportion of Patients with Low-Risk Myelodysplastic Syndrome.
Authors: Luca Malcovati, Matteo G. Della Porta, Anna Galli, Sabrina Boggi, Lucia Malabarba, Daniela Pietra, Francesco Passamonti, Gaetano Bergamaschi, Mario Lazzarino, Mario Cazzola
Journal: Blood (2004)
Treatment of High Risk T-Cell Acute Lymphoblastic Leukemia (T-ALL): Comparison of Recent Experience of the Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG).
Authors: Nita L. Seibel, Barbara L. Asselin, James B. Nachman, Peter Steinherz, Bruce Camitta, Meenakshi Devidas, Harland N. Sather
Journal: Blood (2004)
Haematological parameters in chronic myeloid leukaemia as determinants of clinical manifestations in this disease.
Authors: Nicolas Anthony Othieno-Abinya, Walter Otieno Mwanda, M D Maina, Andrew Oluoch Odhiambo, Sitna A. Mwanzi, Peter Omondi Oyiro
Journal: Journal of Clinical Oncology (2016)

e18529 Background: Chronic myeloid leukaemia (CML) patients commonly complain of abdominal swelling and pain. Presentations like hearing loss, visual impairment and priapism are rare and poorly understood. We aimed to relate clinical presentations with haematologic parameters and BCR-ABL/ABL ratios at diagnosis. Methods: Patients treated at the Nairobi Hospital were studied. We analyzed demographic, physical examination, and laboratory values. Absolute, range, median and mean counts for white blood cells (wbc x109/l), neutrophils (ANCx109/l), platelets (pltx109/l) and haemoglobin (hgb, g/dl) were tested against each of the clinical presentations. Bone marrow blasts and BCR-ABL/ABL ratios at diagnosis were excluded from analysis due to incompleteness of data. Results: Total of 380 patients were included and 450 symptoms analyzed. Abdominal complaints were 207 (46%), nonspecific systemic symptoms 118 (26.2%), subcutaneous nodules 29 (6.4%), joint pains 26 (5.8%) leg swellings 24 (5.3%), bleeding tendency 14 (3.1%), impaired hearing 8 (1.8%), impaired vision 6 (1.3%), priapism 6 (1.3%), tinnitus 2 (0.4%). For abdominal presentations, total wbc (x109/litre) range was 28-703, median 230.5, ANC 17-608, median 160; plt 5-1705, median 348; hgb 2.5-18.5, median 9.7. For vague systemic symptoms wbc was 21-693, median 177; ANC 12-645, median 124; plt 29-2778, median 289; hgb 2.8-16.1, median 9.7. Patients with impaired vision/hearing/CNS manifestations had significantly higher mean total wbc counts (p = 0.03). Mean platelet counts were highest among patients with vague systemic symptoms, but not statistically significant (p > 0.05). There was a trend for patients with high/normal platelet counts to have bleeding tendency compared with those with low/normal counts but not statistically significant (p > 0.05). Conclusions: Clinical presentations of CML cannot be easily explained by haematological values alone, most probably also by complex biologic factors.
RBIO-02. PERSONALIZED SCREENING OF RADIOSENSITIZATION BY A TGF-β SMALL MOLECULE INHIBITOR USING CULTURED EXPLANTS OF HIGH GRADE GLIOMA (HGG) PATIENT SPECIMENS
Authors: Lin Ma, N. Sumru Bayin, Dimitris Placantonakis, Mary Helen Barcellos-Hoff
Journal: Neuro-Oncology (2016)

High-grade gliomas (HGG) manifest profound radioresistance via cell-intrinsic and microenvironmental mechanisms. Transforming growth factor-β (TGF-β) is a key component of the HGG microenvironment, which we have shown enables radioresistance directly by enforcing an effective DNA damage response (DDR), and indirectly by promoting glioma stem cell self-renewal. Heterogeneity of HGG subtypes and patient differences raise the question of general utility of TGF-β inhibition for radiosensitization. Given the impact of microenvironment, we reasoned that personalized radiation biology could be attained by maintaining critical cell interactions. Here, we used HGG explant cultures as a patient-specific platform to test whether a prototypic small molecule inhibitor of the TGF-β type I receptor kinase, LY364947, compromises the DDR. Radiation induced γ-H2AX foci formation was used to assess the molecular recognition of DNA damage, and Sox2 and Notch1 intracellular domain (NICD) were evaluated as glioma stem cell self-renewal signals. Primary HGG (n=7) explants were established on raft inserts for 4 days, treated for 24 hr with LY364947 before irradiating with 2 Gy on day 5. Specimens were fixed 60 min later for immunofluorescence detection of markers. Collectively, radiation-induced γ-H2AX foci were reduced by 37% in LY364947-treated specimens compared to controls. Individual patient specimens ranged from showing no effect of LY364947 to a complete abrogation of radiation-induced foci (2 non-responders and 5 responders), which suggest that cultured HGG explants might be useful for predicting patient-specific radiosensitization with TGF-β antagonists, which are currently in clinical trials. Compared to control explants, self-renewal signal Sox2 increased 2.4 ± 0.3-fold (p<0.01) and NICD1 increased 1.3 ± 0.1-fold (p<0.005) in irradiated explants. Neither marker increased in irradiated HGG specimens treated with LY364947. Our study demonstrates the utility of implementing explants for patient screening, while the apparent benefit of TGF-β inhibition in most irradiated HGG specimens provides further support for clinical trials of TGF-β inhibition during radiotherapy.
ACTR-17. EFFECT OF AGE ON OUTCOME IN THE GLARIUS TRIAL
Authors: Sied Kebir, Elke Hattingen, Christina Schaub, Niklas Schäfer, Joachim Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Theophilos Tzaridis, Oliver Baehr, Martin Proescholdt, Martin Glas, Ulrich Herrlinger
Journal: Neuro-Oncology (2016)

The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma in a 2:1 ratio to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). BEV/IRI prolonged progression-free survival but overall survival (OS) was similar in both treatment arms. Whether elderly patients derive benefit from BEV/IRI treatment is a controversial issue. To address this, the association of age and BEV/IRI treatment was assessed in a subgroup analysis. Patients included in the modified ITT population were grouped according to their age at tumor diagnosis into a <65 years or ≥65 years group. Characteristics (sex, Karnofsky Performance Score (KPS), extent of resection, and mini–mental status examination (MMSE) score) were then evaluated between groups. In a Kaplan-Meier analysis, we compared overall survival (OS) between age groups in each treatment arm. A Cox regression analysis served to detect whether age was an independent prognostic factor. In the BEV/IRI arm, 95 patients were younger than 65 and 21 were at least 65 years old. In the TMZ arm, 41 patients were <65 and 13 ≥65 years old. In each treatment arm, canonical prognostic factors (KPS, extent of resection) were balanced between age groups. Among patients treated with BEV/IRI, those <65 years survived significantly longer than those ≥65 (median OS, 17.5 vs. 13.4 months, p<0.001). Among TMZ treated patients, no significant difference was found between age groups (median OS, 20.0 vs. 17.3 months, p=0.567). In the Cox model, age emerged as an independent prognostic factor in BEV/IRI treated patients only (Hazard Ratio, 2.72, p<0.001). In the GLARIUS trial, patients <65 years derived significantly more benefit from BEV/IRI treatment as compared with elderly patients ≥65. However, the small sample size limits our analysis.
TMIC-23. DIFFERENTIAL EXPRESSION OF THERAPEUTIC TARGETS ACROSS TUMOR MICROENVIRONMENTS AND AT INFILTRATIVE MARGINS IN GLIOBLASTOMA
Authors: James Ross, Daniel Brat, Constantinos Hadjipanayis, Lee Cooper, Merete Wiliams, Alexandros Bouras, Milota Kaluzova, William Dunn, David Gutman, Duc Duong, Myles McCrary
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is highly heterogeneous and micro-environmental diversity may necessitate therapeutically targeting specific tumor regions rather than treating the tumor as a homogenous entity. The diffusely infiltrative properties of GBM result in residual tumor at resection margins in nearly all cases, suggesting that targeting efforts should focus on this region. To identify potential druggable targets at the tumor margin, we utilized fluorescence-guided surgical resection based on 5-ALA, followed by proteomic analysis of individual tumor regions that were precisely defined during surgery. Reverse phase protein array (RPPA) was performed on 206 proteins isolated from the tumor margin, bulk, and perinecrotic regions of 13 genetically defined patient samples (10 GBM, 3AA) in order to identify differentially expressed perturbable molecular pathways or signaling networks. Using ANOVA and post-hoc Tukey-HSD, we identified 37 proteins that were differentially expressed among the three regions. We performed unsupervised hierarchical clustering on these 37 proteins and found that in general, samples from the perinecrotic and bulk regions clustered together and those from the margin clustered together. 25 of these 37 proteins were overexpressed and 12 underexpressed at the tumor margin. Among differentially expressed proteins, we focused further efforts on Akt, PAI-1, and Tyro3. In comparison to the perinecrotic region, Akt and Tyro3 were found to be overexpressed at the tumor margin while PAI-1 was underexpressed at the margin. A common signaling abnormality of GBM is upregulated Akt activity, typically downstream of EGFR, PDGFR or c-Met amplification, PTEN loss or activating mutations in PI3K subunits. Tyro3 is a promising target because of its activation of the PI3K/Akt/mTOR pathway and its role in coagulation. PAI-1 (plasminogen activator inhibitor 1) is a protein that promotes coagulation and could induce intratumoral thrombosis, a defining feature of GBMs. We present differential protein expression patterns among specific tumor microenvironments as potential therapeutic targets.
OS2.5 Long term remission/survival over 8 years in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 dendritic cell-based immunotherapy (phase I)
Authors: S. Phuphanich, C. Wheeler, J. Rudnick, J. Hu, M. Mazer, M. Nuño, C. Sanchez, R. Chu, K. Black, J. Yu
Journal: Neuro-Oncology (2016)
Merck ends trial of potential Alzheimer’s drug verubecestat
Authors: Nigel Hawkes
Journal: BMJ (2017)

The drug giant Merck has pulled the plug on a trial of an Alzheimer’s drug, verubecestat, after early data showed “virtually no chance” that it would work. But a second trial of the same drug continues in patients at an earlier stage of the disease.

Verubecestat was seen as a promising candidate in a field littered with failures, after data published last November showed that the drug reduced the levels of amyloid protein in the spinal fluid of patients and healthy controls who took it for …
Genetic Disruption of the Scaffolding Protein, Kinase Suppressor of Ras 1 (Ksr1), Differentially Regulates GM-CSF-Stimulated Hyperproliferation in Hematopoietic Progenitors Expressing Activating PTPN11 Mutants D61Y and E76K.
Authors: Zhenyun Yang, Sarah Sitarski, Tirajeh Saadatzadeh, Fuqin Yin, Rebecca J. Chan
Journal: Blood (2009)
Differential Regulation of Perforin Expression in CD4+ and CD8+ Cytotoxic T Lymphocytes.
Authors: Hironari Niiya, Jin Lei, Ikuya Sakai, Taichi Azuma, Naoyuki Uchida, Yoshihiro Yakushijin, Takaaki Hato, Shigeru Fujita, Masaki Yasukawa
Journal: Blood (2004)
Efficient Induction of CD34+ Progenitor Cells From Human Bone Marrow Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells with Defined Chemicals
Authors: Yulin Xu, Lizhen Liu, Shan Fu, Lifei Zhang, Yongxian Hu, Senquan Liu, Yingjia Wang, Huarui Fu, Kangni Wu, Haowen Xiao, Xiaohong Yu, Weiyan Zheng, He Huang
Journal: Blood (2011)
Phase I/II dose-finding, safety and efficacy study of radium-223 dichloride in renal cell carcinoma patients with bone metastases
Authors: R. Elaidi, Y.A. Vano, N. Aide, L. Fournier, D. Deandreis, F. Tenenbaum, R. Lebtahi, H. De Clermont-Galleran, L. Albiges, B. Escudier, F. Joly, J. Alexandre, M. Bernardini, S. Baron, J. Arfi-Rouche, C. Noel, E. Braychenko, J. O'Quigley, J. Medioni, S. Oudard
Journal: Annals of Oncology (2016)
Incidence and Determinants of Hepatocellular Carcinoma in Autoimmune Hepatitis: A Systematic Review and Meta-analysis
Authors: Aylin Tansel, Lior H. Katz, Hashem B. El-Serag, Aaron P. Thrift, Mayur Parepally, Mohammad H. Shakhatreh, Fasiha Kanwal
Journal: Clinical Gastroenterology and Hepatology (2017)

The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and associated risk factors among patients with AIH.We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis. The between-study heterogeneity was assessed using I2 statistic.A total of 25 studies (20 papers and 5 abstracts), including 6528 patients, met the eligibility criteria. The median cohort size was 170 patients with AIH (range, 25-1721 patients), followed for a median of 8.0 years (range, 3.3-16.0 years). The pooled incidence rate for HCC in patients with AIH was 3.06 per 1000 patient-years (95% confidence interval, 2.22-4.23; I2 = 51.5%; P = .002). The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 10.07 per 1000 patient-years (95% confidence interval, 6.89-14.70; I2 = 48.8%; P = .015). In addition, 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their HCC diagnosis. The risk of HCC seems to be lower in patients with AIH and cirrhosis than that reported for patients with cirrhosis from hepatitis B, hepatitis C, or primary biliary cholangitis.Based on the increased risked of HCC shown in this meta-analysis, there may be a role for HCC surveillance in patients with AIH and cirrhosis.
High Density Oligonucleotide Array CGH Analysis of CLL Reveals Areas of Recurrent Genomic Gain or Loss.
Authors: Roelandt F.J. Schop, Catherine Mancini, Wee-Joo Chng, Renee C. Tschumper, Diane F. Jelinek, Neil E. Kay, Peter Leif Bergsagel, John D. Carpten, Rafael Fonseca
Journal: Blood (2006)
MPTH-10. LOW INCIDENCE OF R132H IDH-1 MUTATIONS IN LONG TERM GLIOBLASTOMA SURVIVORS
Authors: Ian Whitford, Alexis Demopoulos
Journal: Neuro-Oncology (2016)

Long term survival from glioblastoma multiforme [GBM] is rare. Despite aggressive surgery, chemotherapy and radiation, median survival time is 14.6 months. Nevertheless, small fractions of patients (<20%) survive longer than 36 months and are considered long-term survivors. Established survival predictors include younger age at diagnosis, higher performance scores, greater extent of surgical resection, and chemoradiation therapy. Recently, tumors expressing isocitrate dehydrogenase [IDH] gene mutations have been associated with increased chemotherapy sensitivity and longer survivals. However, several investigators report low IDH mutation frequency in long term survivor cohorts. We retrospectively identified long term GBM survivors from our single-institution database diagnosed between 2005-2013. We excluded patients progressing from lower grade gliomas. We reviewed patient characteristics, including clinical presentation, imaging features, surgical resection, pathology findings, R132H IDH1 immunostains, treatment, and outcomes of these long-term survivors. All initial pathologies were re-reviewed by an independent pathologist. 308 patients were diagnosed during the study period, of whom 30 (9.7%) survived longer than 36 months. Thirteen of these patients are still alive, five off therapy and two on hospice. One patient was lost to follow-up after 43 months. Median overall survival of the cohort was 42 months (range 36-116). The median age of long term survivors at diagnosis was 55.9 years (range 29.1-81.3), 17 (57%) were male, and median KPS at diagnosis was 90 (range 70-90). Seizures were the presenting complaint in 14 patients. Three patients underwent stereotactic biopsy, 24 gross total resection, and 3 subtotal resection. All but one patient received chemoradiation treatment as initial therapy. Five tumors contained IDH1 mutations. Long term survival of patients is generally associated with younger age, higher KPS, gross total resection, seizures at presentation, IDH mutation, and cortical location. While many of our patients possessed these characteristics, the reasons for their long term survivals remain unclear.
A Score Model for Predicting Unsuccessful or Sub-Optimal Peripheral Blood Stem Cell Collections in Multiple Myeloma Based on a Retrospective Analysis of 1,039 Patients Receiving Novel Agents As Induction Therapy and Cyclophosphamide Plus G-CSF As Mobilizing Regimen,
Authors: Pellegrino Musto, Alberto Grossi, Ennio Sarli, Michele Cavo, Federica Leotta, Mario Boccadoro, Antonio Palumbo
Journal: Blood (2011)
Vinflunine (VFL) maintenance therapy in metastatic urothelial carcinoma (UC) after response to 1st line platinum-based chemotherapy (CT): an observational prospective study
Authors: L. Licata, R. Palumbo, C. Teragni, B. Tagliaferri, E. Pozzi, A. Bernardo
Journal: Annals of Oncology (2016)
Pembrolizumab with ChemoRadiotherapy for Muscle Invasive Bladder Cancer: the ANZUP PCR-MIB trial
Authors: A.J. Weickhardt, F. Foroudi, S. Sengupta, P. Grimison, N. Patanjali, S. Leslie, S. Ng, C. Tang, R. Goodwin, E. Hovey, T. Jarvis, C. Chen, A. Herschtal, L. Galletta, S. Sandhu, K.-H. Tai, N. Lawrentschuk, I. Davis
Journal: Annals of Oncology (2016)
Effect of hypoxia on AICAR-induced AMPK activation and cytotoxicity in acute lymphoblastic leukemia cells
Authors: Gilles Leclerc, Guilian Fu, Julio Barredo
Journal: Cancer Research (2008)

2348  Acute Lymphoblastic Leukemia (ALL) is the most common hematological malignancy in children. Despite significant progress in the treatment of ALL, a large number of children continue to relapse and for them, outcome remains poor. Therefore, search for novel treatment strategies is warranted. In our search for novel therapeutic approaches, we identified the AMP activated protein kinase (AMPK), a master regulator of bioenergetics in eukaryotic cells, as a potential target for ALL therapy due to its effects on cell growth, proliferation and cell cycle regulation, and its signaling crosstalk with critical metabolic pathways such as the insulin growth factor receptor (IGF-1R) and the PI3K/Akt/mTOR signaling cascades. Considering that acute leukemias develop in the bone marrow, a hypoxic microenvironment with an oxygen tension (pO2) under 5%, we examined the effect of hypoxia on AMPK signaling and its effects on ALL cell proliferation and survival. The ALL cell models CCRF-CEM (T-lineage) and NALM6 (Bp-lineage) were treated with agents known to activate AMPK (AICAR), or inhibit either ATP synthesis (2-deoxy-D-glucose (2-DG) and oligomycin) or mTOR (rapamycin) and incubated under hypoxic (pO2
Cervical cancer: Awareness and misconceptions of risk factors among lay persons and physicians
Authors: X. Pivot, J.-F. Morère, S. Couraud, C. Touboul, J.-Y. Blay, A.B. Cortot, C. Lhomel, F. Eisinger, L. Greillier, J. Viguier
Journal: Annals of Oncology (2016)
Genes Regulating B-Cell Development and Differentiation Are Mutated in 40% of Pediatric Acute Lymphoblastic Leukemia.
Authors: Charles G. Mullighan, Salil Goorha, Ina Radtke, Christopher B. Miller, Elaine Coustan-Smith, James D. Dalton, Kevin Girtman, Susan Mathew, Jing Ma, Stanley B. Pounds, Xiaoping Su, Ching-Hon Pui, Mary V. Relling, William E. Evans, Sheila A. Shurtleff, James R. Downing
Journal: Blood (2006)