tbuckley/cabot-search huggingface dataset:
Is magnetic resonance useful predicting neoadjuvant response in children with osteosarcoma?
Authors: Marta Zapata-Tarres, Araceli Castellanos-Toledo, Susana Elizalde-Velazquez, Armando Deuña-Flores, Humberto Peña-del-Castillo, Jose de Jesus Figueroa Carbajal
Journal: Journal of Clinical Oncology (2013)

10056 Background: Few prognostic factors had been described for pediatric high-grade osteosarcoma (HGO). Primary tumor necrosis percentage after neoadjuvant chemotherapy, analyzed by pathologists, remains as an important prognostic factor. Magnetic resonance imaging (MRI) has been postulated to predict necrosis in adults. Our aim was therefore to calculate the diagnostic utility of MRI in children. Methods: Prospective, longitudinal and clinical study was performed from September 2011 to January 2012. Twenty two patients (&lt; 18 years), with extremity HGO and no prior chemotherapy treatment were included. All had MRI from diagnosis and just before surgery. We performed a sensibility-specificity analysis comparing percentage of necrosis by MRI vs histological Rosen grades (grades I and II were classified as bad responders; III and IV as good responders). Cut off value for MRI was 90%. Agreement between radiologists was calculated by Cohen´s Kappa coefficient. Results: Average age was 11.7 ± 3.04 (SD), 54.5% were women. All patients received neoadyuvant chemotherapy (cisplatin 120mg/m 2 and adriamicin 75mg/m 2 ). Nine patients had limb-sparing surgery, 8 limb disarticulation and 5 amputations; 72.8% were classified as bad responders by histology. MRI sensibility was 25%, specificity 86.6%, positive predictive value 50% and negative predictive value 68.4%. Kappa correlation coefficient between radiologists was 0,229. Conclusions: Diagnostic utility values in this study were lower than those reported previously. Torricelli, Dyke and Guo reported MRI sensibility of over 70% and specificity ranging from 37% to 87% (similar number of patients). Predictive values were also higher (&gt; 80%). Differences are likely explained by the lack of correlation between radiologists. Our results support the need to establish systematized criteria to measure necrosis by MRI. In order to predict clinical response to chemotherapy in HGO, it is necessary to establish areas and cut off percentages of necrosis for appropriate clinical decision making.
Extracellular vesicles in cancer nanomedicine
Authors: Vadim V. Tarasov, Andrey A. Svistunov, Vladimir N. Chubarev, Samira A. Dostdar, Alexander V. Sokolov, Anna Brzecka, Olga Sukocheva, Margarita E. Neganova, Sergey G. Klochkov, Siva G. Somasundaram, Cecil E. Kirkland, Gjumrakch Aliev
Journal: Seminars in Cancer Biology (2019)
SP0138 Dealing with pain
Authors: R Brioshi
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> A multi-modular approach to treating back pain and fibromyalgy, taking into consideration psycho-social factors. "Chronic pain is not usual pain that simply has a greater duration; it has another quality to it. With chronic pain one has gone beyond the kind of pain that can be forgotten and it becomes one with which one lives constantly...".<sup>1</sup> With these words of Hans Saner, a Swiss philosopher, I wish to present various thoughts on the theme of "Dealing with Pain". Chronic pain is not only a medical problem. At its core is suffering and the patient's individual experience of the illness. To gain some influence over this pain it is both necessary and helpful to elicit interdisciplinary cooperation in many areas, such as medicine, psychology, physiotherapy and ergo-therapy, as well as politics, sociology, anthropology and philosophy. In medicine, as well as in rheumatology, we find ourselves in a phase of paradigmatic change. We are moving from a mono-causal, linear, dualistic and pathology-centred concept of illness and treatment (the thesis), to a multi-facited, holistic and salutogenetic approach (the anti-thesis). Only in the future will we know what the synthesis of this dialectical process will be. In contrast to the old biochemical model, the "new" bio-psycho-social system that had its inception in "gate control theory" of R. Melzack and P. Wall<sup>2</sup> is based upon an interrelatedness of somatic, psychic, social and cultural factors. Influences from both the inner and outer realities of patients have an impact upon the strength of pain, the quality of pain and the worsening of chronic pain. While continuing to respect the dignity of their patients, research and treatment specialists are beginning to interest themselves in the patient's behaviour as well as in their emotional and cognitive reactions to their pain. Research has shown that the following areas are meaningful for a successful rehabilitation: characteristics of the origin and the controlling of pain (cause attribution, locus of control), individual experiences of the illness, cognitive and emotional reactions, coping strategies and influences of variables in the surrounding environment (interactive and structural). Under no circumstance should these observations allow one to ignore other areas under consideration. Specifically, these areas include somatic manifestations, daily stress and work stress. Positive and negative coping strategies will be briefly illustrated in the lecture. The following concepts will be clarified as well: characteristics of the origin of pain (cause attribution), characteristic of the controlling of pain (locus of control), individual illness experiences and the cognitive and emotional reactions to pain. <h3>References</h3> Saner H. Die Anarchie der Stille. Lenos, 1990 Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965
Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1
Authors: Daniel E. Martin-Herranz, Erfan Aref-Eshghi, Marc Jan Bonder, Thomas M. Stubbs, Sanaa Choufani, Rosanna Weksberg, Oliver Stegle, Bekim Sadikovic, Wolf Reik, Janet M. Thornton
Journal: Genome biology (2019)

Epigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data and have emerged in the last few years as the most accurate biomarkers of the aging process. However, little is known about the molecular mechanisms that control the rate of such clocks. Here, we have examined the human epigenetic clock in patients with a variety of developmental disorders, harboring mutations in proteins of the epigenetic machinery.Using the Horvath epigenetic clock, we perform an unbiased screen for epigenetic age acceleration in the blood of these patients. We demonstrate that loss-of-function mutations in the H3K36 histone methyltransferase NSD1, which cause Sotos syndrome, substantially accelerate epigenetic aging. Furthermore, we show that the normal aging process and Sotos syndrome share methylation changes and the genomic context in which they occur. Finally, we found that the Horvath clock CpG sites are characterized by a higher Shannon methylation entropy when compared with the rest of the genome, which is dramatically decreased in Sotos syndrome patients.These results suggest that the H3K36 methylation machinery is a key component of the epigenetic maintenance system in humans, which controls the rate of epigenetic aging, and this role seems to be conserved in model organisms. Our observations provide novel insights into the mechanisms behind the epigenetic aging clock and we expect will shed light on the different processes that erode the human epigenetic landscape during aging.
Response to: ‘MS score in systemic juvenile idiopathic arthritis: suitable for routine use?’ by Chi et al
Authors: Francesca Minoia, Angelo Ravelli
Journal: Annals of the Rheumatic Diseases (2019)

We thank Chi et al 1 for their interest in our diagnostic score for macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA).2 

Chi et al argue that the collection of MAS patient data at the onset of the syndrome and of sJIA patient data not only at the onset of the illness but also during a flare could have caused a selection bias. However, the primary purpose of our analysis was to scrutinise the ability of clinical and laboratory features to discriminate between MAS and active sJIA without MAS. Because the main sJIA manifestations at disease onset or at the time of a flare with ongoing systemic features are clinically similar, we thought that both time points were equally suitable as controls. Note that only 22% of MAS episodes observed in our series developed …
Activity of chemotherapy in inflammatory myofibroblastic tumor (IMT): A retrospective analysis within the Italian Rare Tumours Network (RTR).
Authors: Giacomo Giulio Baldi, Alessandro Gronchi, Bruno Vincenzi, Tommaso Martino De Pas, Maria A. Pantaleo, Lorenzo D'Ambrosio, Giovanni Grignani, Michela Casanova, Andrea Ferrari, Noemi Simeone, Salvatore Provenzano, Angelo Paolo Dei Tos, Marta Sbaraglia, Paola Collini, Gianpaolo Dagrada, Carlo Morosi, Paolo Giovanni Casali, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2019)

e22545 Background: IMT is a rare soft tissue tumour often curable with surgical resection. Nonetheless, in advanced cases a medical therapy is needed. Few data are available on the role of conventional chemotherapy. We report on a retrospective study on the activity of cytotoxic chemotherapy in pts with IMT treated within the RTR. Methods: Patients (pts) of any age with a centrally confirmed diagnosis of IMT treated with anthracycline-based or methotrexate (MTX) and vinorelbine/vinblastine-based regimens between 2008 and 2018 were reviewed. ALK status was evaluated by immunohistochemistry and FISH. Response was assessed by RECIST 1.1. Results: Twenty pts were retrospectively identified (ALK positive = 12, under assessment = 8); median age at the time of treatment start = 38, range = 5-77; disease extent: local disease = 2, locally advanced = 9, metastatic disease = 9. Thirteen pts (65%) received an anthracycline-based regimen, 7 (35%) MTX and vinorelbine/vinblastine. In the anthracycline-based group, 6 (46%) and 7 (54%) pts were treated for localized and advanced disease, respectively. Twelve pts were evaluable for response. Best responses were: 1 CR (8%), 6 PR (50%), 2 SD (17%), 3 PD (25%), for an ORR = 58%. 8 pts received a complete surgical resection at the end of the medical treatment and 6 are disease free. At 39 mos median follow-up, mPFS for 7 pts treated for advanced disease was 5.4 mos (IQR: 1.9-18.8). In the MTX and vinorelbine/vinblastine group, 2 (28%) and 5 (72%) pts were treated for localized disease and advanced disease, respectively. All pts were evaluable for response. Best responses were: 5 PR (50%), 3 SD (30%), 2 PD (20%), for an ORR = 50%. Two pts received a complete surgical resection after the end of chemotherapy and both are disease free. At 56.4 mos median follow-up, mPFS for pts with advanced disease was not reached, with disease progression reported only in 1 pt. Conclusions: Chemotherapy is an option in localised IMT when tumour shrinkage is needed as well as for tumour control in advanced disease. Clearly, its efficacy should be compared with ALK inhibitors, although of course both groups of agents may be resorted to stepwisely in advanced cases in need for medical therapy.
Prognostic value of KRAS in terms of efficacy and safety of bevacizumab as neoadjuvant or conversion treatment in patients with colorectal liver metastasis.
Authors: Pilar Garcia Alfonso, Andrés Jesús Muñoz Martin, Sonsoles Alvarez, M. Carmen Riesco, Montse Blanco Codeisido, Ana Belen Ruperez Blanco, Sara Custodio Cabello, Gonzalo Tapia, Rebeca Mondejar Solís, Miguel Martin
Journal: Journal of Clinical Oncology (2012)

e14058 Background: Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, only a small proportion has initially resectable metastases. Bevacizumab (BEV) added to chemotherapy (CT) is active for metastatic CRC. This study aimed to assess efficacy and safety of BEV as neoadjuvant or conversion treatment in patients with CRC liver metastases. Methods: Observational retrospective review in CRC patients with liver metastases who have undergone neoadjuvant or conversion CT with BEV as first or second line treatment. Results: 34 patients analyzed: 53% male; median age 55; 77% had metastases at diagnosis; ECOG 0-1 (38-62%); primary tumor location: 52% colon, 37% rectum, 11% colon/rectum; 84% had synchronic metastases; 16% initially resectable metastases 9% irresectable and 75% potentially resectable. 77% and 24% received first and second line BEV prior surgery respectively. Complete resection was achieved in 85%. All patients with initially unresectable metastases become resectable. 44% suffered post-operative complications; most frequent being abdominal and wound infection (12-9%). Complete pathologic response of liver metastases was seen in 7% and 61% reached major response. Median OS after surgery was 46 months. Disease free survival (DFS) since surgery was 8.8 months without significant differences between those receiving BEV as first or second line treatment. 88% of patients did not expeirence grade 3-4 toxicity. KRAS mutation was detected in 10 of 26 patients with available KRAS status (39%). Median DFS was significantly longer in wild type wt-KRAS patients compared with those mutated m-KRAS (12 vs 7 months p&lt;0.001) thus confirming KRAS as a prognostic biomarker. Major pathologic response rate was significantly improved in wt-KRAS patients vs m-KRAS (84% vs 25% p&lt;0.001). Conclusions: Neoadjuvant or conversion CT with BEV is an active treatment option for patients with CRC liver metastases with an adequate safety profile and without an apparent increase of surgical complications. While both wt-KRAS and m-KRAS patients benefit from treatment with BEV, wt-KRAS patients obtain greater pathologic response and significant longer DFS.
Towards the elucidation of evolution of out-group aggression
Authors: Nobuhiro Mifune, Dora Simunovic
Journal: Behavioral and Brain Sciences (2019)

We focus on the implications of De Dreu and Gross's findings for the evolutionary perspective on out-group aggression and in-group cooperation. Although their experimental protocols are potentially useful in determining the origins of out-group aggression in humans, they so far provide inconclusive evidence only. We suggest ways of furthering our understanding of the connection between parochial cooperation and intergroup conflict.
Involvement of heavy metal ions in the pathogenesis of cutaneous melanoma: experimental and epidemiologic evidence
Authors: Frank Meyskens, Sun Yang, Dwight Culver, Hoda Anton-culver, Patrick Farmer
Journal: Cancer Research (2007)

86  Our studies on the role of reactive oxygen species in melanoma and the transcriptional response to redox stress has led us to reconsider the role of heavy metals, in conjuction with that of ultraviolet light, in the pathogenesis of melanoma.  Electroparamagnetic resonance, electron microscopy and other experimental techniques suggest that metal ions promote the conversion of melanin pigments in melanocytes and melanoma cells from an anti-oxidant to a pro-oxidant status. We hypothesize that this conversion may be an early pathogenic event which is accompanied by melanosomal disruption and ultimately a source of free radical generation. Previous results from our groups has described high levels of endogenous oxidative stress in several melanoma cell lines, which cause a widespread adaptive response involving increase of a key multifunctional protein redox effector factor-1(also known as apurinic/apyrimidinic endonuclease) that facilitates reduction and DNA binding and subsequent activation of many transcription factors . The involvement of selected heavy metals may be critical to such a process, not only because of its mediated ROS generation, but also because of its potential to interfere with Ref-1 redox reduction activities as well as Ref-1 mediated DNA base excision repair. In a test of such a hypothetical activation, human melanocytes treated with Cu or Cd salts and ultraviolet light evidenced phenotypic changes that resemble dysplatic nevi melanocytes in culture. Also, a re-examination of the non-genetic risk factors for melanoma has identified a large and neglected epidemiology implicating heavy metal exposure. Markedly increased risks for melanoma have been found for populations exposed to heavy metals: printers/lithographers (4 large studies), electrical industry workers ( 3 large studies), and in long term follow-up of hip replacements patients ( 2 large Scandanavian cohorts and a meta-analyses of largely USA reports). Clinical observations (imaging studies) and studies that document the importance of metallothionein expression in primary melanoma and prognosis offers ancillary support for the involvement of metal ions in the pathogenesis of melanoma. Based on these considerations and the high affinity of melanin pigment for metal ions, we propose a significant contribution to the etiology and pathogenesis of melanoma by divalent Cu and Co. This remains to be definitively established.
Developing well-calibrated illness severity scores for decision support in the critically ill
Authors: Christopher V. Cosgriff, Leo Anthony Celi, Stephanie Ko, Tejas Sundaresan, Miguel Ángel Armengol de la Hoz, Aaron Russell Kaufman, David J. Stone, Omar Badawi, Rodrigo Octavio Deliberato
Journal: npj Digital Medicine (2019)

Abstract Illness severity scores are regularly employed for quality improvement and benchmarking in the intensive care unit, but poor generalization performance, particularly with respect to probability calibration, has limited their use for decision support. These models tend to perform worse in patients at a high risk for mortality. We hypothesized that a sequential modeling approach wherein an initial regression model assigns risk and all patients deemed high risk then have their risk quantified by a second, high-risk-specific, regression model would result in a model with superior calibration across the risk spectrum. We compared this approach to a logistic regression model and a sophisticated machine learning approach, the gradient boosting machine. The sequential approach did not have an effect on the receiver operating characteristic curve or the precision-recall curve but resulted in improved reliability curves. The gradient boosting machine achieved a small improvement in discrimination performance and was similarly calibrated to the sequential models.
Predicting methylation-prone CpG islands in human cancer
Authors: Michael McCabe, Eva Lee, Paula Vertino
Journal: Cancer Research (2007)

2839  Aberrant CpG island methylation is responsible for transcriptional silencing of critical regulatory genes in human cancers. While most of the 37,000 human CpG islands remain unmethylated in normal adult cells, select islands (approximately 2-4%) become aberrantly methylated in cancer cells. However, it remains unclear why specific CpG islands are targeted for epigenetic silencing during cancer while others are immune to it. Previous work in our laboratory revealed that 66 (4%) of 1,749 CpG islands underwent de novo DNA methylation in cells engineered to over-express the DNA methyltransferase 1 (DNMT1) gene. Utilizing pattern recognition and supervised machine learning techniques, a classifier was developed to discriminate methylation-prone and methylation-resistant CpG islands based on the frequencies of seven novel DNA patterns. These findings demonstrated that a relatively small fraction of CpG islands are prone to DNA hypermethylation and suggested that CpG islands differ in their intrinsic susceptibility to de novo methylation. In this study, we tested the performance of the classifier by applying it to all CpG islands located on chromosomes 21 and 22 (n=1,357). This analysis predicted 53 CpG islands as methylation-prone. To test the accuracy of these predictions, we analyzed the methylation status of 44 CpG islands on chromosomes 21 and 22 in control and DNMT1-over-expressing cells by methylation-specific PCR. Impressively, the classifier demonstrated an overall correct classification rate of 68% (specificity = 63%; sensitivity = 76%). In order to determine the accuracy of the methylation classifier in human cancer, it was further tested in a panel of 21 normal, immortalized, and malignant breast and lung cell lines. This analysis revealed a 75% overall prediction accuracy (specificity = 68%; sensitivity = 88%). These findings indicate that the methylation susceptibility of a CpG island can be predicted based on its DNA sequence, and suggests that methylation-prone CpG islands inherently possess local cis-acting features which promote their hypermethylation.  This work was funded by the National Institutes of Health (P.M.V.: 2RO1-CA077337) and the Frederick Gardner Cottrell Fellowship Program (M.T.M.).
Comparison between raloxifene and hormone replacement therapy on ambulatory blood pressure and arterial stiffness
Authors: Lilian S. Costa, Monica A. Oliveira, Valeria S. Rubim, Mauricio Wajngarten, José Mendes Aldrighi, Giuseppe M. Rosano, Cantidio Dumond Neto, Otavio C. Gebara
Journal: Circulation (2003)
A Multicenter Retrospective Review of Outcomes of Diffuse Large B Cell Lymphoma (DLBCL) in the Elderly Treated with RCHOP in Australia
Authors: Michael D Ashby, Eliza A Hawkes, Andrew P Grigg, Grace Gard, Zi Yun Ng, Huayi Ellen Huang, Chan Yoon Cheah, Zoe Loh, Allison Mo, Geoff Chong, Andrew B M Lim
Journal: Blood (2017)
FOXM1 Is Associated with Development of Therapeutic Resistance in Multiple Myeloma
Authors: Michael Amatangelo, Maria Ortiz, Paola Neri, Fadi Towfic, Chad Bjorklund, Jian Kang, Erica Sternberg, Nizar J. Bahlis, Matthew Trotter, Anjan Thakurta
Journal: Blood (2017)
The role of STAT1 in tumor killing effect induced by STAT3 inhibition in HNSCC cell lines
Authors: Seon-Hui Shim, Seok-Woo Park, Myung-Whun Sung
Journal: Cancer Research (2006)

3049  Signal transducer and activator of transcription factor (STAT) family proteins are latent cytoplasmic transcription factors that convey signals from cytokine and growth factor receptors to nucleus. We studied about STAT1 and STAT3 among STAT families. The two act pretty differently in cancer cell. STAT1 is associated with apoptosis pathway while STAT3 is tumorigenecity. To investigate a primary role of STAT3 we blocked STAT3 by two Jak kinase inhibitors AG490 (Jak2-STAT3 pathway inhibition) and Jak kinase total inhibitor. First, when we tried to inhibit STAT3 using AG490, significant cell growth arrest was identified. But in case of JAK total inhibitor, there was no cell growth retardation. So we concerned about STAT1 action, which one of the reason why cell growth has no influence after treatment of JAK total inhibitor. To confirm this, we used small interfering RNA of STAT1. In head and neck cancer, suppression of STAT1 by si-RNA resulted in cell growth increasing. Furthermore, the growth inhibitory effect of AG490 was reduced by treatment with si-RNA of STAT1. Also, we observed up-regulation of p-STAT1 by several anti-cancer drugs and identified involvement of STAT1 activation in growth-inhibitory by anti-cancer drugs. In conclusion, tumor killing effect induced by STAT3 inhibition is related with STAT1 action. Thus, when STAT1 is missing, cell death efficiency is decreasing, even though STAT3 is blocked. To improve tumor killing effect in HNSCC, it should be considered not only STAT3 inhibition but also STAT1 activation.