tbuckley/cabot-search huggingface dataset:
IMPS-12CCR2 DEFICIENCY REDUCES THE INFLUX OF CD11b+ MACROPHAGES IN MURINE GLIOMAS
Authors: Defang Luo, Matthew Sarkisian, Jeremy McIntyre, Wenyin Shi, Lawrence Kenyon, Jeffrey Harrison
Journal: Neuro-Oncology (2015)

INTRODUCTION: Glioblastomas (GBMs) are characterized by behavioral aggressiveness and a dismal prognosis despite multimodality therapies. While high numbers of microglia/macrophages are found within GBM, little is known of their specific function within this microenvironment. Mounting evidence indicates a role for these cells in tumor progression and therapy resistance. Microglia/macrophages can constitute as high as 30% of total cells within GBM and there is evidence for the positive correlation between numbers of infiltrating microglia/macrophages and tumor proliferation rate. Sources of these mononuclear cells include brain parenchyma (microglia) and bone marrow (BM). Despite the potential significance of GBM-associated microglia/macrophages to tumor progression and decreased therapeutic efficacy, the mechanisms by which these cells infiltrate GBM are unknown. This localization likely requires the presence of chemokines within the tumor microenvironment and their cognate receptors expressed on microglia/macrophages. While brain-derived microglia and BM-derived macrophages share similar characteristics they also likely exert distinct functions within, and utilize unique mechanisms to gain access to, the GBM microenvironment. It is reported that peripheral BM-derived pro-inflammatory mononuclear cells express the chemokine receptor CCR2 and traffic into inflamed tissues, including irradiated adult brain, in a CCR2-dependent manner. OBJECTIVE: Understand the role of CCR2 in macrophage function within GBM, with the long term goal of inhibiting the pro-tumor promoting activities of these cells. METHODS: We performed immunohistochemical analyses of human GBM sections and analyzed the presence of CCR2+CD11b+ macrophages in CCR2-sufficient and -deficient GL261- and KR158-glioma bearing mice. RESULTS: GBM-associated CD68+ macrophages express CCR2. Prominent numbers of CCR2+CD11b+ macrophages were found within murine GL261 and KR158 gliomas that were distinct from CX3CR1+CD11b+ cells. The tumor localization of the former cells was greatly reduced in CCR2-deficient mice. CONCLUSION: Blocking CCR2 could impact the presence of GBM-associated macrophages, which may in turn decrease tumor growth and/or augment the efficacy of current treatments.
ATPS-71EFFICACY OF TEMOZOLOMIDE IN AN ADULT WITH MEDULLOBLASTOMA, REVIEW OF SERIES OF TWO PATIENTS
Authors: Harsh Parmar, Ruchi Raval, Lajja Majmundar, Sumul Raval
Journal: Neuro-Oncology (2015)

Medulloblastoma is a malignant CNS tumor which is essentially a disease of childhood. It occurs infrequently in adults accounting for less than 1% of all intracranial tumors in adults. Due to the relative infrequency in adults, the clinical characteristics of this disease are not well defined in adults in comparison to children, and optimal treatment is not well established. Complete tumor resection with CSI radiation is the standard of care for treatment of adult medulloblastoma. In contrast to childhood medulloblastoma, the role of chemotherapy in adult population is undetermined. A number of chemotherapy agents in treatment of pediatric medulloblastoma have been evaluated and used including vincristine, CCNU, cisplatin, carboplatin, and cyclophosphamide. We report a case series of two patients diagnosed with medulloblastoma who underwent surgical resection followed by radiation therapy. Both patients underwent 24 cycles of chemotherapy with temozolamide over a period of 2 years with minimal toxicity. They were monitored with multiple MRIs of brain which have not revealed any disease recurrence so far rendering one patient disease free for eight and a half years and the other for six months. Very few cases of medulloblastoma treated with temozolamide have been reported. Our case series shows the antitumor effect of temozolamide in treatment of medulloblastoma with minimal toxicity. Most of the literature is based on retrospective analysis rather than randomized studies due to the small number of adult cases reported with this disease compared to the pediatric population. The optimal treatment regimen is not well established for this tumor and because of its rarity a multi-institutional clinical trial will be necessary to define the best treatment.
Bevacizumab Immune Complexes Induce Thrombocytopenia and Thrombosis in Mice Transgenic for Human IgG Receptor FcYIIa
Authors: Ali Amirkhosravi, Todd V Meyer, Liza Robles-Carillo, Florian Langer, Theresa Robson, Hina Desai, Monica Davila, Mildred Amaya, John L. Francis
Journal: Blood (2008)
STEM-21DISRUPTION OF FACILITATES CHROMATIN TRANSCRIPTION (FACT) SYNERGIZES WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) INHIBITION AND PREFERENTIALLY TARGETS GLIOBLASTOMA STEM CELLS
Authors: Josephine Kam Tai Dermawan, Masahiro Hitomi, Justin Lathia, Jeremy Rich, Katerina Gurova, George Stark, Monica Venere
Journal: Neuro-Oncology (2015)
Biologic activity of LSD1 inhibition by novel tranylcypromine structural analogues in prostate cancer cells.
Authors: Simon J. Crabb, Annette L Hayden, Rosemary A Strivens, Hanae Benelkebir, A Ganesan, Graham Packham
Journal: Journal of Clinical Oncology (2012)

82 Background: Hormonal strategies to inhibit androgen receptor (AR) signalling remain inadequate and so novel approaches are urgently required. Lysine (K)-specific demethylase 1A (LSD1), is an epigenetic AR co-activator which modifies chromatin structure through de-methylation of histone H3 lysine 9 at androgen response elements to activate transcriptional expression of AR target genes. LSD1 is over-expressed and a poor prognostic factor in prostate cancer. We have synthesised novel analogues of the monoamine oxidase (MAO) inhibitor tranylcypromine as LSD1 inhibitors to exploit MAO and LSD1 sequence homology. Methods: We utilised prostate cancer cell line models to investigate the biological effect of LSD1 inhibition using tranylcypromine analogues. Results: Chemical inhibition of LSD1 was effective in inhibiting cell proliferation in prostate cancer models with around 1000 fold greater potency for synthesised analogues over tranylcypromine in LNCaP prostate cancer cells. Chemical inhibition of LSD1 induced the predicted histone methylation changes consequent on LSD1 inhibition of mono- and di-methylation of histone H3 lysine 9. In addition LSD1 depletion, AR depletion and reduced expression of the AR target gene prostate-specific antigen was demonstrated. Fractional effect assays demonstrated synergistic interactions in cell proliferation assays for tranylcypromine analogues with the androgen receptor antagonists bicalutamide and MDV3100. Conclusions: Our data demonstrate biological activity of LSD1 inhibition in prostate cancer cells with depletion of AR signalling using optimised structural analogues of established drugs for non-cancer indications. Therapeutic targeting of LSD1 for prostate cancer would represent a novel therapeutic paradigm for this disease.
Comparison of 12-Month Treatment Costs for Patients with Advanced Phase Chronic Myeloid Leukemia (CML) in China: Imatinib (IM) vs. Chemotherapy (Chemo) Plus Interferon-(IFN) in Accelerated Phase (AP) CML and IM vs. Chemo in Blast Crisis (BC) CML.
Authors: Zi Chen, Chun Wang, Weiwei Feng
Journal: Blood (2007)
Trichotillomania and Bipolar Disorder
Authors: Verinder Sharma, Christine Baczynski
Journal: American Journal of Psychiatry (2017)

Chamberlain (1), published in the September 2016 issue of the Journal, on the assessment and treatment of trichotillomania.As the authors point out, psychiatric comorbidity is the rule rather than the exception in patients with trichotillomania.In one study (2), approximately 55% of patients with trichotillomania met DSM-III-R criteria for a lifetime diagnosis of a mood disorder, including bipolar disorder in a small number of patients.While major depressive disorder is the most common mood disorder, the relationship between trichotillomania and bipolar disorder remains unclear (3).Over the past few years, we have successfully treated several women at our perinatal psychiatric clinic who were comorbid for bipolar II disorder and trichotillomania (4).Interestingly, all of our patients (N55) had experienced exacerbation of symptoms of trichotillomania immediately after giving birth.All patients failed to respond to trials of selective serotonin reuptake inhibitors (SSRIs), and two patients failed to respond to olanzapine.However, there was a robust and sustained response to lithium (in three patients) or lamotrigine (in two patients) monotherapy.Studies have shown a correlation between changes in reproductive physiology and the onset or exacerbation of symptoms of trichotillomania in humans and hair plucking behavior (barbering) in mice (S.Husk, 2010 master's thesis).Childbirth is also a well-recognized trigger of onset or exacerbation of bipolar disorder.As the authors point out, SSRIs are not generally effective in trichotillomania.Moreover, the use of these drugs in patients with bipolar disorder may lead to further mood instability.Available literature, although limited to anecdotal reports, suggests that antidepressants should be avoided in favor of mood stabilizers for management of trichotillomania and bipolar disorder comorbidity.
ABT-737 Is a Useful Component of Combinatory Chemotherapies for Chronic Myelogenous Leukemias with Diverse Drug Resistance Mechanisms.
Authors: Junya Kuroda, Shinya Kimura, Michael Andreeff, Eishi Ashihara, Yuri Kamitsuji, Andreas Strasser, Masafumi Taniwaki, Taira Maekawa
Journal: Blood (2007)
Selective reoperation for locally recurrent or metastatic pancreatic ductal adenocarcinoma following primary pancreatic resection.
Authors: Ryan Michael Thomas, Mark Joseph Truty, Jason B. Fleming, Peter W. T. Pisters, Jeffrey Edwin Lee, David C. Rice, Wayne Lewis Hofstetter, Robert A. Wolff, Gauri R. Varadhachary, Huamin Wang, Matthew H.G. Katz
Journal: Journal of Clinical Oncology (2012)

252 Background: Resection of recurrent disease in malignancies such as colorectal cancer has been shown to prolong survival but resection for recurrent pancreatic ductal adenocarcinoma (PDAC) is viewed as futile. We sought to identify factors that may be associated with prolonged survival following resection of recurrent PDAC. Methods: A retrospective review of a prospectively-maintained pancreatic tumor database was performed to identify all patients from 1992-2010 who developed recurrent PDAC after intended surgical cure. The group was screened for those who underwent a second operative procedure with curative intent. Clinicopathologic features were correlated with disease-free interval (DFI) and survival to identify factors that may be associated with prolonged survival in patients undergoing reoperation for PDAC. Results: Of 700 patients who underwent resection for PDAC, 426 (61%) recurred after a median of 8mo and 21 (5%) of those had a locoregional [pancreas (n=5), other (n=2)] or distant [lung (n=7), liver (n=6), brain (n=1)] recurrence that were selected for a second, potentially curative operation. Sixteen of 21 patients received chemotherapy prior to reoperation. Those selected had a single, technically resectable lesion, good performance status, and prolonged median DFI compared to patients not selected (22mo v. 8mo, p&lt;0.01). The median DFI from initial resection to recurrence for those with lung (52mo) or locoregional (41mo) recurrence was longer than those with liver recurrence (10.5mo, p=0.03). The interval between reoperation and second recurrence in patients with lung metastasis (NR) was longer than for liver (6mo) or locoregional recurrence (7.5mo, p=0.02). Patients still alive include 4/7 of lung, 3/7 of locoregional, and 1/6 of liver recurrences with a median follow-up after reoperation of 30mo, 14mo, and 18.5mo, respectively. Conclusions: Patients who develop a solitary recurrence of PDAC in the lung after a long disease-free interval should be considered for reoperation. Those with recurrence in other sites are likely to re-recur relatively quickly after reoperation regardless of disease-free interval.
Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein
Authors: Yulei Chen, Siyuan Zhang, Qizhi Wang, Xiaobo Zhang
Journal: Journal of Hematology & Oncology (2017)

The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.
A randomized study of granulocyte-colony stimulating factor applied during and after chemotherapy in patients, with poor risk myelodysplastic syndromes : A final report from the Hovon Cooperative Group.
Authors: GJ Ossenkoppele, B van der Holt, Geg Verhoef, Smgj Daenen, LF Verdonck, P Sonneveld, PW Wijermans, J van der Lelie, Wlj van Putten, B Lowenberg
Journal: Blood (1998)
“Large Pericardial Effusions as a Manifestation of Graft Versus Host Disease: a Single Institution Retrospective Study”.
Authors: Maxim Norkin, Voravit Ratanatharathorn, Lois Ayash, Muneer H. Abidi, Lawrence G. Lum, Zaid Al-Kadhimi, Joseph P. Uberti
Journal: Blood (2009)
Long-Term Outcome of All-Trans-Retinoic-Acid(ATRA)+Intensive Chemotherapy in Acute Promyelocytic Leukemia(APL),
Authors: Taiichi Kyo, Takeshi Okatani, Kouhei Kyo, Mitsuhiro Itagaki, Ryouta Imanaka, Koji Iwato, Hidkeki Asaoku, Yuuta Katayama
Journal: Blood (2011)
Efficacité d’une stratégie multifactorielle de préparation colique chez les patients diabétiques: un essai randomisé
Authors: N. Musquer
Journal: Endoscopy (2016)

Le diabète est un facteur reconnu de mauvaise préparation colique. C’est pourquoi cette équipe espagnole a cherché à tester la mise en place d’un programme spécifique de préparation pour les patients diabétiques dans le cadre d’une étude monocentrique prospective, randomisée, contrôlée, en simple aveugle.
U.K. experience of sunitinib malate in the treatment of metastatic renal cell carcinoma: Predictors of response from clinical practice.
Authors: Rebecca Allison Goranova, Bojidar Bojidarov Goranov, Ian David Pedley, Ashraf Azzabi, Alison Humphreys, Rhona McMenemin, John A. Frew
Journal: Journal of Clinical Oncology (2012)

455 Background: Sunitinib gained NICE approval in March 2009 as first line treatment for metastatic renal cell carcinoma (mRCC) and UK experience of use of Sunitinib is growing. The North of England Cancer Network (NECN) was the first cancer network in the UK to approve the use of Sunitinib in July 2007 and has the longest UK experience with this drug. The clinical outcomes of the NECN patients are presented. Methods: Data was collected and analysed regarding all patients started on Sunitinib from 01/07/2007 to 30/09/2010. Follow up extended to 28/02/2011. Previously published predictors of response were compared to the NECN data to check applicability in this population. Results: 129 patients were identified with a median age of 63 years (range 21-87), 67% were male and WHO performance status was 0, 1 or 2 (33%, 51%, 16%). 80% of patients had nephrectomy (60% radical) and 22% had prior systemic treatment. Median PFS was 10 months (range 0.25-27). Median OS (from Sunitinib initiation) was 17 months (range 0.25 - 47). Performance status was significantly associated with PFS and OS. The median number of treatment cycles was 5 (range 0.25-27). 64% of patients were dose reduced and 9% had a schedule modification to minimise toxicity. 21% of patients had a delay of 4 weeks or more which was not detrimental to median PFS. Dose reduction at treatment initiation was associated with a significant decrease in OS. 11.6% of patients required treatment for hypothyroidism which was associated with a significant improvement in PFS and OS. 15.5% of patients required treatment for hypertension, which was associated with an improvement in OS, but not PFS. Conclusions: PFS in the NECN population is similar to trial data. Strategies to deal with side effects, including dose reduction (after treatment initiation), treatment delay and schedule changes, did not adversely affect PFS. Performance status 0, the development of new hypertension or new hypothyroidism can be regarded as markers of good prognosis in this population. Initial dose reduction should be avoided as this adversely affects prognosis.
Depletion of Ptch2 Activates Canonical and Non-Canonical HH Signaling within the Niche Leading to Myeloproliferation, Stem Cell Exhaustion and Accelerates JAK2V617F Driven Disease
Authors: Claudius Klein, Anabel Kuhn, Sandra Kissel, Marie Follo, Anna Lena Illert, Dietmar Pfeifer, Heike L Pahl, Robert A.J. Oostendorp, Justus Duyster, Christine Dierks
Journal: Blood (2015)
ATPS-57INTRA-ARTERIAL ADMINISTRATION IMPROVES TEMOZOLOMIDE DELIVERY AND EFFICACY IN A MODEL OF INTRACEREBRAL METASTASIS, BUT HAS UNEXPECTED BRAIN TOXICITY
Authors: Leslie Muldoon, Michael Pagel, Joao Prola Netto, Edward Neuwelt
Journal: Neuro-Oncology (2015)

We tested the hypothesis that intra-arterial (IA) infusion of temozolomide into the internal carotid artery would safely improve drug delivery to brain and enhance chemotherapy efficacy in a chemosensitive rat brain tumor model. Quantitative autoradiography after 25 µCi 14C-temozolomide was given by oral, intravenous, or IA route of administration, or IA with osmotic blood-brain barrier disruption (BBBD) (n = 5-7 per group) showed that both IA and IA/BBBD administration increased drug delivery in tumor by over 3-fold compared to normal brain (P < 0.02), and also significantly elevated delivery throughout the infused right hemisphere. Temozolomide (20 mg/kg; ∼150 mg/m2) increased median survival when given by oral (25.5 days), intravenous (25.5 days), or IA (33 days) route of administration, compared to 17.5 days in untreated controls (n = 8 per group; overall P < 0.0001). Survival time after IA temozolomide was significantly longer than all other groups (P < 0.01 for all comparisons). BBBD temozolomide was toxic in the efficacy study, but there was no evidence of symptomatic neurotoxicity in rats given IA temozolomide. After these promising animal results, a 49 year old male with glioblastoma multiforme who failed all standard therapy received temozolomide 100 mg/m2 IA. Upon initiation of the second course of IA infusion the patient had increased heart rate, blood pressure, and rash, and the procedure was terminated without sequelae. Follow up IA infusion of temozolomide diluent in normal rats showed damaged cerebrovasculature as determined by dye leakage. We conclude that under the current formulation temozolomide is not safe for IA infusion.
Absolute Lymphocyte Count Assessed During Routine Follow-up Is a Risk Factor for Relapse Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Patients with Diffuse Large B-Cell Lymphoma.
Authors: Luis Porrata, David J Inwards, Stephen M Ansell, Ivana Micallef, Patrick L Johnston, William Hogan, Svetomir Markovic
Journal: Blood (2009)
Quality of Life After Transcatheter Aortic Valve Replacement
Authors: Robert O. Bonow, Patrick T. O’Gara
Journal: JAMA Cardiology (2017)

Suzanne V. Arnold, MD, MHA; John A. Spertus, MD, MPH; Sreekanth Vemulapalli, MD; Zhuokai Li, PhD; Roland A. Matsouaka, PhD; Suzanne J. Baron, MD, MSc; Amit N. Vora, MD, MPH; Michael J. Mack, MD; Matthew R. Reynolds, MD, MSc; John S. Rumsfeld, MD, PhD; David J. Cohen, MD, MSc
Once more with feeling: On the explanatory limits of the GANE model and the missing role of subjective experience
Authors: Jeffrey R Huntsinger, Justin Storbeck
Journal: Behavioral and Brain Sciences (2016)

We applaud Mather and colleagues' model, which emphasizes the neurobiological pathways by which affective arousal tunes attention and memory. This commentary offers a friendly discussion of several potential limitations of the theory. We suggest the model is strong when predicting task-driven demands but is limited when predicting the impact of individual biases, interpretations, and experiential feelings.
Validating ECOG Performance Status as a Prognostic Factor in Brazilian Patients with Pulmonary Adenocarcinoma
Authors: Rafael C. Bitton, Luiz G. C. A. De Lima, Felipe S. R. Roitberg, Cristiane Mesquita, Renata E. Martins, Cheng T. Yen, Ricardo M. Terra, Evandro S. Mello, Gilberto De Castro Jr.
Journal: Journal of Thoracic Oncology (2015)
Effect of an antibiotic checklist on length of hospital stay and appropriate antibiotic use in adult patients treated with intravenous antibiotics: a stepped wedge cluster randomized trial
Authors: F.V. van Daalen, J.M. Prins, B.C. Opmeer, M.A. Boermeester, C.E. Visser, R.M. van Hest, J. Branger, E. Mattsson, M.F.M. van de Broek, T.C. Roeleveld, A.A. Karimbeg, E.A.F. Haak, H.C. van den Hout, M.A. van Agtmael, M.E.J.L. Hulscher, S.E. Geerlings
Journal: Clinical Microbiology and Infection (2017)
A 15-Year-Old Girl With Unexplained Intracranial Hypertension
Authors: Paula Wu Feng, Adeniyi A. Fisayo
Journal: JAMA Pediatrics (2017)

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Comparative Analysis of Outcomes of Allogeneic Peripheral Blood Stem Cell Transplantation From Related and Unrelated Donors for Adults with Hematologic Malignancies
Authors: Chunji Gao, Xiaohong Li, Honghua Li, Wenrong Huang, Xiaoxiong Wu, Jian Ma, Jian Bo, Zhihong Wang, Yongbin Cao, Yu Zhao, Li Yu, Wanming Da
Journal: Blood (2010)
Low Incidence of Hepatic Veno-Occlusive Disease after Fractionated Doses of Mylotarg and Autologous or Allogeneic Stem Cell Transplantation.
Authors: Hassan Farhat, Emmanuel Raffoux, Francoise Isnard, Nathalie Contentin, Anne Laure Taksin, Herve Dombret, Sylvie Castaigne, Philippe Rousselot
Journal: Blood (2005)