tbuckley/cabot-search huggingface dataset:
Clinical benefit of palliative treatment of cancer cachexia with medroxyprogesterone acetate (MPA)
Authors: D. Tassinari, E. Flamini, B. Poggi, F. Fochessati, M. Fantini, L. Fabbri, P. Turci, F. Monti, A. Polselli, M. Maltoni
Journal: Journal of Clinical Oncology (2004)

8213 Background. Although progestins seem to represent the treatment of choice of primary cancer cachexia, the outcomes of a palliative treatments still remain undefined. In our trial both the relationships between clinical benefit (CB), appetite improve (AI), weigh gain (WG), performance status (PS) and astenia (As), and the predictive role of 7- and 21-day CB, AI, WG, PS, As, or basal Interleukin- (IL6), Tumor Necrosis Factor alpha (TNFa), and Interferon-gamma (INFg) were investigated. Methods. All the patients with solid, not-hormone-sensitive neoplasm and a weigh loss greater than 10% for cancer cachexia were considered eligible and enrolled into the trial. All the patients were treated with oral MPA acetate 1000 mg/day, and were evaluated before entering the trial and on day 7, 21 and 42 for CB, AI, and As using a VAS scale; PS was evaluated using the Karnofsky scale. Before entering the trial, basal IL6, TNFa and INFg were evaluated in all the patients. Results. 31 patients with mean age of 71 years (range 55–92) were enrolled into the trial. The median follow up was 75 days and the median survival was 83 days (calculated using the Kaplan Meyer test). An improve in CB was linked with AI (p<0.001) and PS (p=0.07) using the Fisher exact test, while no significant links were observed between CB and WG or AS. Neither a predictive value of 7- and 21-day evaluation of CB, AI, WG, PS, and As, nor a predictive value of basal IL6, TNFa and INFg for 42-day CB response were identified using the Mann Whitney not-parametric test. Conclusions. Our data seem to confirm a lack of correlation between CB or quality of life and the two main indexes of activity of MPA; although AI and CB seem to be linked, AI could not be considered enough to favour a CB. Moreover, the lack of relationships between the outcomes of a treatments with progestins and basal cytokines could suggest a mechanism of action of progestins that could be not only related with the well-known cytokines cascade. (supported by IOR). No significant financial relationships to disclose.
Efficacy and safety of dose-adjusted lenalidomide therapy in relapsed/refractory myeloma patients with renal impairment
Authors: Shigeki Ito, Maki Asahi, Tatsuo Oyake, Wataru Izumida, Yasuhiko Tsukushi, Takeshi Sugawara, Yoji Ishida
Journal: Annals of Oncology (2015)
Feasibility Study of a Dose Dense Induction Regimen of High Dose Cytarabine (HiDAC) and Gemtuzumab Ozogamicin (Mylotarg™) for Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia.
Authors: Arati V. Rao, David A. Rizzieri, Joseph O. Moore, Carlos DeCastro, Louis F. Diehl, Amy P. Abernethy, McLean Jordan, Patty Davis, Emily Edmonds, Jon P. Gockerman
Journal: Blood (2005)
PET-CT Adapted Therapy after 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis. Preliminary Results in 102 Patients
Authors: Astrid Pavlovsky, Santiago Pavlovsky, Isolda Fernandez, Lucia Zoppegno, Ider Cerutti, Miguel Arturo Pavlovsky, Virginia Prates, Ana Basquiera, Claudia Corrado, Gustavo Milone, Maria Cabrejo, Horacio Fernandez Grecco, Graciela Avila, Viviana Flores Dutrus, Karina Gumpel, Vanina Cabanne, Silvia Saba, Francisco Lastiri
Journal: Blood (2008)
Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: A multivariate analysis of the French Sarcoma Group database
Authors: A. Italiano, F. Delva, V. Brouste, P. Terrier, M. Trassard, J. Michels, F. Collin, J. Coindre, J. Blay, B. Bui
Journal: Journal of Clinical Oncology (2009)

10504 Background: The SMAC meta-analysis failed to demonstrate that adjuvant chemotherapy (AC) significantly improves overall survival (OS) in adult patients with localised resectable soft-tissue sarcoma (STS). We report here the analysis of the impact of AC in the population of STS patients included in the prospective database of the French Sarcoma Group. Methods: Between 1980 and 1999, 2,029 pts with STS were admitted to one of the 20 tertiary cancer centers of the GSF for the management of a first tumoral event and were included prospectively in a comprehensive database. 152 pts were excluded from the study because of metastatic disease at diagnosis. All the cases were reviewed by the pathology subcommittee of the GSF. Tumor grade was assessed according to the FNCLCC system based on tumor differentiation, mitotic count, and necrosis. Results: 283 pts (14.5%) had grade 1, 736 (39.5%) grade 2 and 858 (46%) grade 3 tumors. 1,102 pts (59%) had extremity tumors. The commonest pathological subtypes were MFH 22.5%, liposarcoma 18%, leiomyosarcoma 13%, and synovial sarcoma 10%. 1,122 pts (60%) received adjuvant radiotherapy. AC was delivered in 16 grade 1 pts (6%), 167 grade 2 pts (23%) and 323 grade 3 pts (38%). The majority of patients who received AC had tumors with a deep topography (91%) and/or &gt; 5 cm (75%) and/or located in the limbs (61%). The median follow-up was 9 years. The 5 year-OS was 90% for grade 1 pts, 63% for grade 2 pts and 46% for grade 3 pts. On multivariate analysis ( table 1 ), AC was strongly associated with improved metastasis-free survival (MFS) (5 year MFS: 53% vs 47%, HR 0.7 [0.5–0.9], p=0.003) and overall survival (OS) (5 year OS: 56% vs 44%, HR 0.7 [0.5–0.8], p=0.004) in grade 3 pts. This association was not observed in grade 2 pts (5 year MFS: 73% vs 72%, HR 0.9 [0.6–1.4], p=0.9; 5 year OS: 73% vs 65%, HR 0.7 [0.5–1.1]). Conclusions: This large cohort-based analysis with long-term follow-up indicates that FNCLCC grade 3 pts are likely to benefit from AC. [Table: see text] [Table: see text]
New metrics for the Lancet Standing Commission on Liver Disease in the UK
Authors: Roger Williams, Graeme Alexander, Richard Aspinall, Joanne Bosanquet, Ginette Camps-Walsh, Matthew Cramp, Natalie Day, Anil Dhawan, John Dillon, Jessica Dyson, James Ferguson, Graham Foster, Richard Gardner, Sir Ian Gilmore, Lesley Hardman, Mark Hudson, Deirdre Kelly, Andrew Langford, Stephen Liversedge, Kieran Moriarty, Philip Newsome, John O'Grady, Rachel Pryke, Liz Rolfe, Harry Rutter, Stephen Ryder, Marianne Samyn, Nick Sheron, Alison Taylor, Jeremy Thompson, Julia Verne, Andrew Yeoman
Journal: The Lancet (2016)
Prognostic Analysis of Pre-Transplant CD26-Positive Lymphocytes and CD26bright/CD45RO-Positive Memory T-Cell Levels in Patients Receiving an Autologous Hematopoietic Progenitor-Cell Transplant.
Authors: Martin Hildebrandt, Hella Gollasch, Kirstin Rautenberg, Bernd Doerken, Wolf-Dieter Ludwig
Journal: Blood (2007)
Pattern of Mir-155 and PU.1 Expression in CLL/SLL and Aggressive Lymphomas
Authors: Tomas Stopka, Karin Vargova, Hana Huskova, Pavel Burda, Nikola Curik, Petra Vlckova, Vojtech Kulvait, Vit Pospisil, Filipp Savvulidi, Emanuel Necas, Marek Mraz, Sarka Pospisilova, Jiri Mayer, Josef Karban, Petra Obrtlikova, Marek Trneny
Journal: Blood (2011)
Stem Cell Mobilization and Egress of AML Blasts from the Bone Marrow Are Both Regulated by MT-MMP-Mediated Activation of MMP-2.
Authors: Leah A. Marquez-Curtis, Neeta Shirvaikar, Loree M. Larratt, A. Robert Turner, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek
Journal: Blood (2005)
In vitro treatment of non-small cell lung cancer cells with temsirolimus and/or docetaxel: Does alternating the sequence affect the outcome?
Authors: C. Huang, J. Misra, P. J. Van Veldhuizen, F. Farassati
Journal: Journal of Clinical Oncology (2011)

e13515 Background: Lung cancer is the leading cause of cancer related death in the US with 5-year survival of less than 1% in advance stages of disease. There is a need to find new treatment strategies to improve the survival outcomes. Mammalian target of rapamicin (mTOR) is a downstream regulatory protein of the PI3K/Akt signal transduction pathway. This is a common pathway for a several cell surface receptors including insulin-like growth factor receptor (IGFR) and epidermal growth factor receptor (EGFR). The activation of these receptors through PI3K/Akt pathway is essential in cell proliferation, angiogenesis and anti-apoptosis process. Several therapeutic agents that inhibit these receptors have shown to be active in the treatment of diverse types of cancers. Docetaxel (D) is commonly used in the treatment of lung cancer. We decided to explore the potential role of mTOR inhibition using temsirolimus (T) in the treatment of lung cancer in a lung cancer cell line (LCCL) model. The experiments also sought to elucidate the optimal sequencing of these drugs. Methods: Adenocarcinoma LCCL 2122 and 1437 were plated and exposed to temsirolimus 1000nM and docetaxel 100nM. The cell viability was measured by optical density (OD) at 24, 48 and 72h. We then tested the sequence of D for 48h followed by addition of T for another 24h and the reverse in both LCCL. Results: The combination of TD had the highest inhibition of cell proliferation after 48 hours of exposure in both 2122 (mean OD 0.31 vs. control 0.86 p=0.0003) and 1437 LCCL (mean OD 0.55 and control 0.988 p=0.001). The sequence of D followed by T decreased OD greater than the T followed by D sequence in 1437 LCCL after 72 hours (mean 0.3789 vs. 0.7175). The OD was decreased in both sequences in 2122 cell line compared to control but there was no difference between either sequence. Conclusions: The combination of TD seems to be an active regimen when tested in 2 adenocarcinoma LCCL. The sequence of these agent showed that D followed by T is more active in 1437 LCCL. Further studies in animal model exploring the combination of this regimen using the combination of TD followed by T may help determine if this is a feasible combination in the treatment of lung cancer.
PTU-066 Non-invasive assessment of systemic haemodynamics to determine variceal bleeding risk in cirrhotic patients: Abstract PTU-066
Authors: K A Rye, G Mortimore, A Austin, J Freeman
Journal: Gut (2010)

<h3>Introduction</h3> Variceal bleeding is one of the most severe complications of portal hypertension. Universal endoscopic variceal screening is recommended and primary prophylaxis given based on oesophageal variceal size. Risk of bleeding also relates to other factors such as portal pressure, liver disease severity, and red wale markings at endoscopy. Currently there is no non-invasive way of measuring portal pressure or bleeding risk. The aim of this study was to evaluate whether non-invasive assessment of systemic haemodynamics in cirrhosis can identify bleeding risk in portal hypertension. <h3>Methods</h3> We studied 29 cirrhotic patients. Systemic haemodynamics and baroreceptor sensitivity (BRS) were assessed non-invasively using the Finometer® (TNO instruments, Amsterdam), and analysed with Beatscope® software. Spontaneous BRS was assessed by studying the relationship between inter-beat variability and beat-to-beat changes in systolic blood pressure. Portal pressure was assessed by measurement of the hepatic venous pressure gradient (HVPG). Gastroscopy assessed variceal size, Japanese score and 1-year probability of bleeding according to the NIEC index. <h3>Results</h3> 69% male, median age 47 (42–55) years, Child-Pugh (CP) score 6 (Class A 18, Class B 10, Class C 1) and MELD 10 (8–13). 90% alcoholic cirrhosis, 66% abstinent. HVPG correlated positively with variceal size (r=0.64, p&lt;0.001), and all measures of variceal bleeding risk (Abstract 066). Significant positive correlations were seen with CI, HR and SVR and variceal bleeding risk, while a significant negative correlation was seen with BRS and bleeding risk. HVPG correlated positively with both CI (r=0.53, p=0.005) and HR (r=0.62, p&lt;0.001) and negatively correlated with BRS (r=−0.69, p&lt;0.001). BRS correlated negatively with HR (r=−0.56, p=0.002). <h3>Conclusion</h3> Non-invasive assessment of systemic haemodynamics in cirrhosis may be useful in predicting HVPG and bleeding risk from oesophageal varices. This study highlights that other factors such as baroreceptor sensitivity are important in determining portal pressure and bleeding risk and may open up potential new treatment options.
735. Functional Restoration of Dystrophin Protein in HiPSC-Derived Skeletal Myotubes and Cardiomyocytes After CRISPR/Cas9-Mediated Deletion of 530-725kb of DMD
Authors: Courtney S. Young, Michael R. Hicks, Natalia V. Ermolova, Haruko Nakano, Majib Jan, Shahab Younesi, Atsushi Nakano, Stanley F. Nelson, M. Carrie Miceli, Melissa J. Spencer, April D. Pyle
Journal: Molecular Therapy (2016)

Duchenne muscular dystrophy (DMD) is typically due to frameshifting mutations in the DMD gene encoding dystrophin. Loss of dystrophin protein results in progressive muscle degeneration and premature death. Approximately 60% of DMD patients have frameshifting mutations in a hotspot region within exons 45-55 in the rod domain of dystrophin. Genotype/phenotype assessments have revealed that in-frame deletion of exons 45-55 leads to the milder, allelic disease, Becker muscular dystrophy. This finding suggests that restoration of the reading frame by targeting exons 45-55 could treat ~60% of DMD patients to greatly reduce disease severity. We have developed a platform using clustered regularly interspaced short palindromic repeats (CRISPR) and- associated protein (Cas9) gene editing to achieve this purpose. We have utilized CRISPR/Cas9-mediated deletion and rejoining of up to 725kb to restore the reading frame in DMD human induced pluripotent stem cells (hiPSCs). This is the largest deletion shown to date in DMD. Clonal hiPSC lines containing the exon 45-55 deletion were differentiated to disease relevant types, such as cardiomyocytes and skeletal muscle myotubes, which had restored dystrophin protein. We demonstrated, for the first time, that the internally deleted dystrophin generated by CRISPR/Cas9 was functional and improved membrane integrity, reduced miR31 expression, and restored the dystrophin glycoprotein complex in vitro and after engraftment of skeletal muscle cells in vivo. This gene editing platform restores the reading frame for the majority of DMD patients and offers potential as an ex vivo correction for stem cell therapy or for use in vivo.
Acute and Chronic Posttraumatic Stress Symptoms in the Emergence of Posttraumatic Stress Disorder
Authors: Richard A. Bryant, Mark Creamer, Meaghan O’Donnell, David Forbes, Alexander C. McFarlane, Derrick Silove, Dusan Hadzi-Pavlovic
Journal: JAMA Psychiatry (2016)

Little is understood about how the symptoms of posttraumatic stress develop over time into the syndrome of posttraumatic stress disorder (PTSD).To use a network analysis approach to identify the nature of the association between PTSD symptoms in the acute phase after trauma and the chronic phase.A prospective cohort study enrolled 1138 patients recently admitted with traumatic injury to 1 of 4 major trauma hospitals across Australia from March 13, 2004, to February 26, 2006. Participants underwent assessment during hospital admission (n = 1388) and at 12 months after injury (n = 852). Networks of symptom associations were analyzed in the acute and chronic phases using partial correlations, relative importance estimates, and centrality measures of each symptom in terms of its association strengths, closeness to other symptoms, and importance in connecting other symptoms to each other. Data were analyzed from March 3 to September 5, 2016.Severity of PTSD was assessed at each assessment with the Clinician-Administered PTSD Scale.Of the 1138 patients undergoing assessment at admission (837 men [73.6%] and 301 women [26.4%]; mean [SD] age, 37.90 [13.62] years), strong connections were found in the acute phase. Reexperiencing symptoms were central to other symptoms in the acute phase, with intrusions and physiological reactivity among the most central symptoms in the networks in terms of the extent to which they occur between other symptoms (mean [SD], 1.2 [0.7] and 1.0 [0.9], respectively), closeness to other symptoms (mean [SD], 0.9 [0.3] and 1.1 [0.9], respectively), and strength of the associations (mean [SD], 1.6 [0.3] and 1.5 [0.3] respectively) among flashbacks, intrusions, and avoidance of thoughts, with moderately strong connections between intrusions and nightmares, being upset by reminders, and physiological reactivity. Intrusions and physiological reactivity were central in the acute phase. Among the 852 patients (73.6%) who completed the 12-month assessment, overall network connectivity was significantly stronger at 12 months than in the acute phase (global strength values, 6.57 vs 7.60; paired difference, 1.03; P < .001). The network associations among the reexperiencing symptoms were strengthened at 12 months, and physiological reactivity was strongly associated with the startle response, which was also associated with hypervigilance. Strong connectivity among emotional numbing, detachment from others, and disinterest in activities as well as moderately strong links among irritability (anger), concentration deficits, and sleep disturbance were found.As time elapses after trauma, fear circuitry and dysphoric PTSD symptoms appear to emerge as connected networks. Intrusive memories and reactivity are centrally associated with other symptoms in the acute phase, potentially pointing to the utility of addressing these symptoms in early intervention strategies.
T4 Global spread of mycobacterium abscessus clones amongst cystic fibrosis patient
Authors: DM Grogono, JM Bryant, D Rodriguez-Rincon, I Everall, KP Brown, P Moreno, D Verma, E Hill, J Drijkoningen, CS Haworth, SR Harris, D Ordway, J Parkhill, RA Floto
Journal: Thorax (2016)

<h3>Introduction</h3> Lung infections with <i>Mycobacterium abscessus, </i>a species of multidrug resistant nontuberculous mycobacteria, have increased in frequency worldwide, emerging as an important global threat to individuals with cystic fibrosis (CF) where they cause accelerated inflammatory lung damage and death. <i>M. abscessus </i>was previously thought to be independently acquired by susceptible individuals from the environment. However, using whole genome sequencing and detailed epidemiological analysis of a cohort of patients attending the CF centre at Papworth Hospital, we found strong evidence for transmission between patients. We therefore sought to examine the mechanism of acquisition of <i>M. abscessus </i>in CF individuals across the world. <h3>Methods</h3> We undertook whole genome sequencing on 1080 isolates from 517 patients from the UK, US, the Republic of Ireland, mainland Europe and Australia. This was then correlated with clinical metadata and phenotypic functional analysis. <h3>Results</h3> Our genomic analysis revealed that the majority of infections are from densely clustered <i>M. abscessus</i> genotypes with low levels of diversity, indicating a high level of human associated spread. Moreover, the phylogeny reveals the presence of three recently emerged dominant circulating clones that have globally spread. We found that these clones are associated with worse clinical outcomes and show increased virulence in both cell-based and mouse infection models. Within patients we found evidence of genetic diversity and evolutionary adaptation through the processes of convergent evolution and hypermutation. <h3>Conclusions</h3> The majority of <i>M. abscessus</i> infections in patients with Cystic Fibrosis are caused by genetically related clusters, indicating recent patient-to-patient transmission despite conventional infection control measures. Transmission appears to have facilitated evolution of <i>M. abscessus </i>from an environmental organism into a transmissible human pathogen. This work was supported by The Wellcome Trust grant 098051 (JMB, SH, JP) and 107032AIA (DG, RAF) The Medical Research Council (JMB), The UK Cystic Fibrosis Trust (DMG, DR-R, IE, JP, RAF), Papworth Hospital (DMG, KPB, CSH, RAF), NIHR Cambridge Biomedical Research Centre (RAF), and The UKCRC Translational Infection Research Initiative (JP).
Abstract P3-11-13: Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer
Authors: Yaewon Yang, Tae-Yong Kim, Seock-Ah Im, Bhumsuk Keam, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Hyeong-Gon Moon, Wonshik Han, In Ae Park, Dong-Young Noh
Journal: Cancer Research (2015)

Abstract Background: Triple negative breast cancer (TNBC) shows poor prognosis despite their higher response rate to neoadjuvant chemotherapy (NAC). Response to NAC such as pathologic complete response (pCR) is a well-known useful prognostic marker for relapse and overall survival. Pre-chemotherapy baseline higher Ki-67 is a positive predictive marker for higher pCR rate but a negative prognostic marker for relapse free survival (RFS) and overall survival (OS). After short course of NAC, Ki-67 index changed in response to the treatment. The purpose of this study is to investigate the prognostic role of Ki-67 index change between before and after the long course of NAC in TNBC patients. Patients and Methods: Patients with clinical stage II or III breast cancer treated with NAC at Seoul National University Hospital were enrolled and their clinicopathological findings including Ki-67 index were reviewed retrospectively. The definition of Ki-67 threshold of high was ≥14% in current study. TNBC definition was adopted from 2011 St Gallen Consensus Panel. Results: From Jan 2009 to Dec 2010, a total of 183 patients received NAC. Among them, 46 (25.1%) were TNBC. The pCR rate (19.6% vs 9.5%, P=0.069) and the objective response rate (complete response + partial response) (76.1% vs 70.8%, P=0.153) were higher in TNBC group than in non-TNBC group. The RFS was not different between the two groups (3 year 77.3% vs 75.4%, P=0.877). The change of Ki-67 index from high (≥14%) to low (&amp;lt;14%) was significantly associated with longer RFS in only in TNBC group. As for TNBC patients with high Ki-67 index at diagnosis, RFS of those whose Ki-67 index changed to low after NAC were significantly longer than that of whose Ki-67 index remained high (3 year RFS 87.2% vs 54.5%, P=0.036). In non-TNBC group, change of Ki-67 index was not significantly associated with RFS (P=0.245). The initial Ki-67 index itself (high vs. low) was not associated with RFS in both TNBC and non-TNBC group (P=0.726 and P=0.523 respectively). Conclusion : The change of Ki-67 index from high to low is associated with longer RFS in TNBC. Ki-67 index change between before and after the NAC can be used for further discrimination of TNBC as a prognostic marker. Citation Format: Yaewon Yang, Tae-Yong Kim, Seock-Ah Im, Bhumsuk Keam, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Hyeong-Gon Moon, Wonshik Han, In Ae Park, Dong-Young Noh. Change of Ki-67 after long course of neoadjuvant chemotherapy as prognostic factors in patients with stage II, III triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-13.