tbuckley/cabot-search huggingface dataset:
The palliative care network as a model of continuity of care in oncologic departments
Authors: D. Tassinari, B. Poggi, A. Fabbri, L. Massa, S. Nicoletti, A. Pecci, G. Ricci, W. Raffaeli
Journal: Journal of Clinical Oncology (2006)

18518 Background: Although medical oncology and palliative care are often distant dimensions in the treatment of patients with cancer, it is a common notion that an integration could improve the outcome in a comprehensive assistance to the patient. Methods: To create a Palliative Care Network (PCN) in our Department, we promote the creation of a multidisciplinary team (MT) with oncologists (2), palliativists (1), psychologists (1), social workers (2) and nurses (3) with the aim of favouring the continuity of care along all the phases of the disease. The MT gathers the competences of the oncologic and palliative care units, and is coordinated by the responsible of the supportive and palliative care unit of the district. All the patients were evaluated before entering into the project and classified in three levels with different care burden. In all the patients admitted to the PCN a palliative support is planned since the early phases of metastatic disease. The palliative care project are weekly updated by the MT. The outcomes of the PCN are evaluated every six months for activity and annually for efficacy. Results: 4589 patients have been admitted in 2003–2005 period (419 in Hospice). 2441 (53.2%), 1533 (33.4%) and 615 (13.4%) patients were classified respectively in the three increasing severity levels, and an “intensive” palliative approach was needed in 2547 (55.5%) patients. The main problems referred by the patients or their families were symptoms control, pain control, the need of psychological or social support, the need of a continuity of care along the terminal phases of the disease. Preliminary data seem to suggest a positive impact of the shared approach against the symptoms of advanced or terminal disease, and an interesting level of satisfaction by patients and caregivers seems to be confirmed in a preliminary assessment. Conclusions: The continuity of care is considered an index of the quality of care and an integrated model of palliative care should be elaborated in every oncologic district; oncologic departments seem to represent the ideal dimension where favouring an integration between medical oncology and palliative care and every effort should be made to realize this kind of integration. No significant financial relationships to disclose.
Virus Biomarkers: Rapid Visual Screening and Programmable Subtype Classification of Ebola Virus Biomarkers (Adv. Healthcare Mater. 2/2017)
Authors: Mustafa Balcioglu, Muhit Rana, Mustafa Salih Hizir, Neil M. Robertson, Kashfia Haque, Mehmet V. Yigit
Journal: Advanced Healthcare Materials (2017)

Since early diagnosis of Ebola virus disease (EVD) may halt the transmission and increase the probability of survival, it is vital to develop costeffective, highly sensitive and selective biosensing platforms that allow for both the detection and phenotyping of Ebolavirus subtypes. In article 1600739, Mehmet V. Yigit and co-workers report a highly programmable and sensitive approach that enables the visual detection and classification of four Ebolavirus subtypes in human urine in sixteen different combinations using a single gold nanoprobe.
Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites
Authors: Mendi J. Muthinja, Johanna Ripp, Janina K. Hellmann, Tamas Haraszti, Noa Dahan, Leandro Lemgruber, Anna Battista, Lucas Schütz, Oliver T. Fackler, Ulrich S. Schwarz, Joachim P. Spatz, Friedrich Frischknecht
Journal: Advanced Healthcare Materials (2017)

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream.
Yttrium-90 Radiolabeled Daclizumab, An Anti-CD25 Monoclonal Antibody, Provides Effective Therapy for Refractory and Relapsed Hodgkin's Lymphoma,
Authors: Thomas A. Waldmann, John Janik, John C Morris, Kevin Conlon, Deirdre O'Mahony, Stefania Pittaluga, Elaine S. Jaffe, Martin Brechbiel, Chang H Paik, Clara Chen, Millie Whatley, Thomas A Fleisher, Jeffrey White, Donn Stewart, Suzanne Fioravanti, Carolyn Goldman, Bonita Bryant, Jean Decker, Richard Junghans, Jorge A. Carrasquillo
Journal: Blood (2011)
Animal Models of Thrombosis Help Predict the Human Therapeutic Concentration of PRT54021, a Potent Oral Factor Xa Inhibitor.
Authors: Keith Abe, Gail Siu, Susan Edwards, Pei Hua Lin, Bing Yan Zhu, Ulla Marzec, Stephen Hanson, Yvonne Pak, Stanley Hollenbach, Uma Sinha
Journal: Blood (2006)
Complete Remission of Immunocytoma without Graft Versus Host Disease Caused by Allo-HLA-DP Specific T Cells.
Authors: Caroline E. Rutten, Simone A.P. van Luxemburg-Heijs, Inge Jedema, Mirjam Heemskerk, Roelof Willemze, J.H. Frederik Falkenburg
Journal: Blood (2006)
High Alloreactive Potential of Central Memory T-Lymphocytes Expressing a Suicide Gene for the Cure of Hematologic Malignancies.
Authors: Shin Kaneko, Sara Mastaglio, Attilio Bondanza, Maurilio Ponzoni, Luca Aldrighetti, Salvatore Toma, Marina Radrizzani, Simona La Seta Catamancio, Fabio Ciceri, Toshiro Nagasawa, Claudio Bordignon, Chiara Bonini
Journal: Blood (2006)
In patients with severe sepsis, hydrocortisone did not prevent progression to septic shock
Authors: Bram Rochwerg, Gordon Guyatt
Journal: Annals of Internal Medicine (2017)

Source Citation Keh D, Trips E, Marx G, et al; SepNet-Critical Care Trials Group. Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016;316:1775-85. 27695824
HMGA2–FOXL2 Axis Regulates Metastases and Epithelial-to-Mesenchymal Transition of Chemoresistant Gastric Cancer
Authors: Jiaqiang Dong, Rui Wang, Gui Ren, Xiaowei Li, Jingbo Wang, Yi Sun, Jie Liang, Yongzhan Nie, Kaichun Wu, Bin Feng, Yulong Shang, Daiming Fan
Journal: Clinical Cancer Research (2017)

Purpose: Chemoresistance is the main cause of treatment failure in cancer and is associated with distant metastases and epithelial-to-mesenchymal transition (EMT). This study was aimed to explore the mechanism of metastases and EMT in chemoresistant gastric cancer.Experimental Design: A key molecular pathway was identified via gene profiling and a bioinformatic analysis in a chemoresistant gastric cancer model. The roles of FOXL2, HMGA2, and ITGA2 were validated via loss-of-function and gain-of-function experiments in vitro and in an orthotopic gastric cancer animal model. The regulation of FOXL2 by HMGA2 was explored via immunoprecipitation and luciferase reporter assays. The expression of these proteins in gastric cancer tissues was examined by IHC.Results: HMGA2 and FOXL2 directly regulated the metastasis and EMT of chemoresistant gastric cancer. The interaction between HMGA2 and pRb facilitated the transactivation of FOXL2 by E2F1, and ITGA2 was the downstream effector of the HMGA2-FOXL2 pathway. HMGA2, FOXL2, and ITGA2 were associated with the TNM classification and staging of gastric cancer and were increased in metastatic lymph nodes and distant metastases. Increased HMGA2, FOXL2, and ITGA2 levels were associated with reduced overall survival periods of patients with gastric cancer.Conclusions: This study demonstrated that the transactivation of FOXL2 driven by interactions between HMGA2 and pRb might exert critical effects on the metastases and EMT of chemoresistant gastric cancer. Blocking the HMGA2-FOXL2-ITGA2 pathway could serve as a new strategy for gastric cancer treatment. Clin Cancer Res; 23(13); 3461-73. ©2017 AACR.
Treatment of Peripheral T-Cell Lymphoma (PTCL) with High-Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT).
Authors: Min Kyoung Kim, Shin Kim, Seoung Sook Lee, Sun Jin Sym, Dae Ho Lee, Sang We Kim, Seongsoo Jang, Chan Jeong Park, Hyun Sook Chi, Joo Ryung Huh, Cheolwon Suh
Journal: Blood (2006)
Outcomes in Obese and Overweight Acute Myeloid Leukemia (AML) Patients Receiving Chemotherapy Dosed According to Actual Body Weight
Authors: Erika M. Gallagher, Marc Earl, Jun-Yen Yeh, Karissa Kusick, Jaclyn Kruse, Caitlin Swann, April Smith, Randall Davis, Anjali S. Advani, Matt Kalaycio, Edward A. Copelan, Mikkael A. Sekeres
Journal: Blood (2011)
IMCT-13LYMPHOPENIA IN ELDERLY PATIENTS WITH GLIOBLASTOMA TREATED WITH RADIATION AND TEMOZOLOMIDE
Authors: Joe Mendez, Ashwin Govindan, Jiayi Huang, Jian Li Campian
Journal: Neuro-Oncology (2015)

BACKGROUND: Management of elderly patients with high grade glioma often includes radiation therapy (RT) +/- temozolomide (TMZ). A previous report showed that standard RT/TMZ resulted in severe lymphopenia in 40% of patients (median age of 57) with an associated shorter survival (Grossman, 2011). Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancer. This study is designed to evaluate whether elderly patients (age ≥65) with glioblastoma (GBM) develop severe treatment related lymphopenia (TRL) after RT +/- TMZ and whether TRL is associated with reduced survival. METHODS: Elderly patients (age ≥65) newly diagnosed with GBM and followed-up at Washington University (2000-2013) were eligible. Radiation parameters and serial total lymphocyte counts (TLC) were collected. RESULTS: Seventy-seven patients were eligible: median KPS 70, median age 71 years (range 65 - 86) with 57% of patients >70 years, 52% female, 32% received RT <6 weeks, 42% had a baseline TLC <1000 cells/mm3 with 78% taking glucocorticoids. Baseline TLC prior to treatment was 1100 cells/mm3 with a fall by 45% at 2 months (median 600, range 100-2500). At 2 months, 22% of patients had a drop in TLC to <500 cells/mm3 (median 400, range 100-400). Patients with TLC <500 cells/mm3 at 2 months had a shorter survival than those with TLC ≥500 cells/mm3 with a median overall survival of 7.6 vs 10.1 months, respectively. Consistent with literature, an increased survival was found on multivariable analysis with MGMT methylation and gross total resection. We also found that higher baseline TLC was associated with increased survival. CONCLUSIONS: This is the first study to look at the development of TRL and its association with survival in elderly GBM patients. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes.
Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer
Authors: T. Koie, H. Yamamoto, A. Okamoto, S. Hatakeyama, A. Momose, I. Iwabuchi, T. Yoneyama, Y. Hashimoto, N. Kamimura, C. Ohyama, Y. Saijo
Journal: Journal of Clinical Oncology (2009)

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m 2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.
Immune Thrombocytopenia Mediated by Anti-GPIbα Antibodies May Occur Via an FcR-Independent Pathway: A Potential Explanation for Refractory Cases to IVIG Therapy.
Authors: Michelle L. Webster, Ebrahim Sayeh, Min Crow, Pingguo Chen, Bernhard Nieswandt, John Freedman, Heyu Ni
Journal: Blood (2005)
Differential signaling networks of Bcr–Abl p210 and p190 kinases in leukemia cells defined by functional proteomics
Authors: S Reckel, R Hamelin, S Georgeon, F Armand, Q Jolliet, D Chiappe, M Moniatte, O Hantschel
Journal: Leukemia (2017)

The two major isoforms of the oncogenic Bcr–Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated. Whereas the AP2 adaptor complex that regulates clathrin-mediated endocytosis interacts preferentially with p190, the phosphatase Sts1 is enriched with p210. Stronger activation of the Stat5 transcription factor and the Erk1/2 kinases is observed with p210, whereas Lyn kinase is activated by p190. Our findings provide a more coherent understanding of Bcr–Abl signaling, mechanisms of leukemic transformation, resulting disease pathobiology and responses to kinase inhibitors.
Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC).
Authors: Hans J. Hammers, Elizabeth R. Plimack, Jeffrey R. Infante, Marc S. Ernstoff, Brian I. Rini, David F. McDermott, Albiruni R. A. Razak, Sumanta Kumar Pal, Martin Henner Voss, Padmanee Sharma, Christian K. Kollmannsberger, Daniel Yick Chin Heng, Jennifer L. Spratlin, Yun Shen, John F. Kurland, Paul Gagnier, Asim Amin
Journal: Journal of Clinical Oncology (2014)

4504 Background: There is a need for agents that result in durable responses and improved tolerability in patients (pts) with mRCC. Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has shown activity in mRCC. Combining nivolumab + ipilimumab, a fully human monoclonal antibody to CTLA-4, showed encouraging clinical activity and acceptable safety in advanced melanoma. We report preliminary results of the combination in mRCC. Methods: Pts with mRCC (favorable/intermediate MSKCC score; Karnofsky performance status ≥80%; untreated or any number of prior therapies) were randomized to receive nivolumab 3 mg/kg + ipilimumab 1 mg/kg (arm N3 + I1) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg (arm N1 + I3) IV Q3W for 4 doses then nivolumab 3 mg/kg IV Q2W until progression/toxicity. The primary objective was to assess safety/tolerability; secondary objective was to assess antitumor activity. Results: Pts were randomized to N3 + I1 (n=21) and N1 + I3 (n=23). Most pts (n=34; 77%) had prior systemic therapy (N3 + I1: 16; N1 + I3: 18). Treatment-related adverse events (AEs) were seen in 39/44 pts (89%); 7 pts (16%; N3 + I1: 2; N1 + I3: 5) discontinued due to any-grade related AEs. Grade 3–4 related AEs occurred in 19 pts (43%; N3 + I1: 5; N1 + I3: 14), most commonly ↑ lipase (16%, n=7), ↑ ALT (11%, n=5), diarrhea (9%, n=4), colitis (5%, n=2), ↑ amylase (5%, n=2). No grade 3–4 pneumonitis was seen. Objective response rate (ORR) was 29% (N3 + I1) and 39% (N1 + I3) (Table). Duration of response (DOR) was 4.1+ to 22.1+ wks (all 6 responses ongoing) in N3 + I1, and 6.1+ to 18.3+ wks (8/9 responses ongoing) in N1 + I3. Responses occurred by first tumor assessment (wk 6) in 67% of responding pts in both N3 + I1 and N1 + I3. Stable disease (SD) was seen in 7 (33%) pts (N3 + I1) and 9 (39%) pts (N1 + I3). Conclusions: Nivolumab + ipilimumab showed acceptable safety and encouraging antitumor activity in mRCC, with most responses ongoing. Follow-up, expansion cohorts at these doses and an additional dose cohort (nivolumab 3 mg/kg + ipilimumab 3 mg/kg) are being assessed. Clinical trial information: NCT01472081. Arm N3 + I1 n=21 Arm N1 + I3 n=23 ORR, n (%) 6 (29) 9 (39) SD, n (%) [duration, wks] 7 (33) [6+ to 25+] 9 (39) [6+to 26.1] DOR, range (wks) 4.1+ – 22.1+ 6.1+ – 18.3+ PFS, range (wks) 4.7+ – 28.1+ 4.3 – 26.1
Immunotolerant indoleamine‐2,3‐dioxygenase is increased in condyloma acuminata
Authors: Z. Xie, M. Zhang, W. Xiong, H.Y. Wan, X.C. Zhao, T. Xie, H. Lei, Z.C. Lin, D.S. Luo, X.L. Liang, Y.H. Chen
Journal: British Journal of Dermatology (2017)

The tryptophan‐depleting enzyme indoleamine‐2,3‐dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune‐associated skin diseases. To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T‐cell mitogen (PHA)‐stimulated T‐cell proliferation were explored. IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV− site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO‐competent epidermal cells from warts could transform tryptophan. In addition, these IDO‐competent epidermal cells could inhibit PHA‐stimulated T‐cell proliferation. The addition of an IDO inhibitor, 1‐methyl‐d‐tryptophan, restored the inhibited T‐cell proliferation. Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.
Advancing the Needs of Patients in the Trump Era
Authors: Robert Steinbrook, Mitchell H. Katz, Rita F. Redberg
Journal: JAMA Internal Medicine (2017)

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MiR-182 promotes cancer invasion by linking RET oncogene activated NF-κB to loss of the HES1/Notch1 regulatory circuit
Authors: Alf Spitschak, Claudia Meier, Bhavani Kowtharapu, David Engelmann, Brigitte M. Pützer
Journal: Molecular Cancer (2017)

Dominant-activating mutations in the RET proto-oncogene, a receptor tyrosine kinase, are responsible for the development of medullary thyroid carcinoma (MTC) and causative for multiple endocrine neoplasia (MEN) type 2A and 2B. These tumors are highly aggressive with a high propensity for early metastasis and chemoresistance. This attribute makes this neoplasia an excellent model for probing mechanisms underlying cancer progression.The expression level of miR-182 was measured in MTC tumor specimens and in TT cells by real-time RT-PCR. TT cells and modified NThy-ori 3.1 that stably express RETM918T were used to investigate RET-dependent regulation of miR-182. Identification and validation of miR-182 targets and pathways was accomplished with luciferase assays, qRT-PCR, Western blotting and immunofluorescence. In vitro, overexpression and knockdown experiments were carried out to examine the impact of miR-182 and HES1 on invasion and migration.We found that miR-182 expression is significantly upregulated in MTC patient samples and tumor-derived cell lines harboring mutated RET. Inhibition of RET oncogenic signaling through a dominant-negative RET∆TK mutant in TT cells reduces miR-182, whereas overexpression of RETM918T in NThy-ori 3.1 cells increases miR-182 levels. We further show that overexpression of this miRNA in NThy.miR-182 cells promotes the invasive and migratory properties without affecting cell proliferation. MiR-182 is upregulated after RET induced NF-κB translocation into the nucleus via binding of NF-κB to the miR-182 promoter. Database analysis revealed that HES1, a repressor of the Notch pathway, is a target of miR-182, whose upregulation correlates with loss of HES1 transcription in MTC tissue samples and mutant RET cell lines. Moreover, we demonstrated that the 3'UTR of the HES1 mRNA bearing the targeting sequence for miR-182 clearly reduced luciferase reporter activity in cells expressing miR-182. Decreased expression of HES1 promotes migration by upregulating Notch1 inhibitor Deltex1 and consequent repression of Notch1.We demonstrate a novel mechanism for MTC aggressiveness in which mutated RET/NF-κB-driven expression of miR-182 impedes HES1 activation in a negative feedback loop. This observation might open new possibilities to treat RET oncogene associated metastatic cancer.