tbuckley/cabot-search huggingface dataset:
Assessment of the uterus with three-dimensional ultrasound in women undergoing ART
Authors: Sotirios H. Saravelos, Kannamannadiar Jayaprakasan, Kamal Ojha, Tin-Chiu Li
Journal: Human Reproduction Update (2016)

A detailed assessment of the uterus forms a pivotal part of the ART treatment process. The emergence of three-dimensional ultrasound (3D US) has provided clinicians with a highly powerful tool in this respect. Assessments with 3D US range from the reconstruction of anatomical planes elusive to conventional US, to the objective measurement of anatomical volumes and vascularization parameters. However, despite the ever increasing number of publications emerging in the literature, the question of which aspects of 3D US are of most clinical value remains a topic of debate. The objective of this review is to dissect which aspects of the 3D US assessment of the uterus are supported by a strong level of evidence to date, and should therefore be incorporated into current routine clinical practice. We conducted a systematic search of the PubMed database up to May 2016, using a combination of text words and Medical Subject Headings (MeSH) pertaining to the 3D US assessment of the uterus. All articles published in the English language were screened to ascertain relevance to women of reproductive age; further citations were retrieved through manual reference list searching. A multitude of predominantly observational studies were identified, which concerned a vast variety of 3D US uterine assessments. All articles unequivocally praised the non-invasive, cost-effective, highly acceptable and objective nature of 3D US. Studies regarding the value of assessing the endometrial volume and vascularization prior to embryo transfer appeared conflicting and inconsistent. Studies regarding the imaging of uterine pathology and identification of intratubal and intrauterine devices consistently reported high rates of diagnostic accuracy. A recent RCT did not show an improvement in clinical outcomes when comparing 3D versus 2D US during embryo transfer. However, preliminary studies suggested that 3D US is superior in determining the site of implantation, particularly in ambiguous cases such as interstitial and angular pregnancies. Finally, pilot studies have suggested that the further integration of 3D and possibly 4D US with surgical interventions of the uterus may be a promising prospect. 3D US may prove to be an invaluable tool in the assessment of the uterus within the context of ART. Currently, the aim should be to highlight the aspects of 3D US that are most evidence-based and valuable for patients, and to incorporate these into routine clinical practice.
Abstract 4110: Inhibition of angiopoietin 1/2 and c-MET impairs metastatic potential in a patient derived xenograft of renal carcinoma
Authors: Ashley Orillion, Remi Adelaiye-Ogala, Li Shen, Eric Ciamporcero, Sheng Yu Ku, Swathi Ramakrishnan, May Elbanna, Sreenivasulu Chintala, Roberto Pili
Journal: Cancer Research (2015)

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and diagnoses have been on the rise since the 1990s. While patients with early stage ccRCC have more than a 50% survival rate over four years, those with advanced stage disease have a less than 10% chance of 5 year survival. In our current study, we utilized an angiopoietin 1/2 inhibitor (Amgen 386) and a novel c-MET inhibitor in murine models grafted with human derived xenografts (PDX) with a high metastatic penetrance. Our goal was to assess the ability of these compounds to prolong survival via metastatic inhibition. Methods: Seven week old SCID mice were implanted either subcutaneously or orthotopically with human ccRCC PDX RP-R-02LM. Approximately one month post implantation, mice were started on treatment with Angiopoietin 1/2 inhibitor (Amgen 386), c-met inhibitor (compound A) or a combination of the two. Amgen 386 was administered twice a week subcutaneously at 5.6mg/kg. Compound A was given daily via oral gavage at 30mg/kg. As a survival study, treatment was continued until the mice reached a point where they needed to be euthanized or they were found dead. Results: In our metastatic PDX model, RP-R-02LM, Amgen386 single agent treatment and combination c-MET inhibitor and Amgen386 treatment significantly reduced metastases significantly, p = 0.0075 and p = 0.0001 respectively. Further, an ongoing survival study has shown that at four and a half months post implantation both single agent and combination treatments prolong the survival of mice implanted with RP-R-02LM, a highly metastatic PDX. Conclusions: Our preliminary results suggest that Amgen386 in combination with a novel c-MET inhibitor are significantly inhibiting the spread of metastases and prolonging survival. This indicates a potential use for combination therapy in treating patients with ccRCC in advanced stages of the disease. Citation Format: Ashley Orillion, Remi Adelaiye-Ogala, Li Shen, Eric Ciamporcero, Sheng Yu Ku, Swathi Ramakrishnan, May Elbanna, Sreenivasulu Chintala, Roberto Pili. Inhibition of angiopoietin 1/2 and c-MET impairs metastatic potential in a patient derived xenograft of renal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4110. doi:10.1158/1538-7445.AM2015-4110
Acute Otitis Media — The Long and the Short of It
Authors: Margaret A. Kenna
Journal: New England Journal of Medicine (2016)

Acute otitis media is the second most common reason for a child to visit his or her primary care physician and the most common reason for prescribing an antibiotic agent to a child.1 Over the past 40 years, substantial progress has been made in understanding the epidemiology, bacteriology, risk factors, and natural history of acute otitis media.2 The introduction of pneumococcal vaccines, the 7-valent vaccine (PCV7) in 2000 and the 13-valent vaccine (PCV13) in 2010, has resulted in a decrease in the incidence of acute otitis media attributable to the pneumococcal vaccine serotypes.3 Despite this decrease, acute otitis media remains . . .
Hyperglycemia in Patients with Acute Myeloid Leukemia Is Associated with Increased Hospital Mortality.
Authors: Naeem A. Ali, James M. O’Brien, William Blum, Rebecca B. Klisovic, Guido Marcucci, Gary Phillips, Clay B. Marsh, Stanley Lemeshow, John C. Byrd, Michael R. Grever
Journal: Blood (2006)
Simultaneous Targeting of Aurora Kinases and Bcr-Abl by the Small Molecule Inhibitor PHA-739358 Is Effective in Imatinib-Resistant Mutations Including T315I.
Authors: Artur Gontarewicz, Stefan Balabanov, Gunhild Keller, Riccardo Colombo, Alessio Graziano, Carsten Bokemeyer, Walter Fiedler, Jurgen Moll, Tim Brummendorf
Journal: Blood (2007)
Clinical Status Longer than One Year Post-Transplantation in 4 Recipients of Non-T-Cell-Depleted HLA-Haploidentical Transplantation Based on Feto-Maternal Microchimerism.
Authors: Takao Yoshihara, Akira Morimoto, Hiroshi Kuroda, Hiroyuki Ishida, Toshihiko Imamura, Etsuko Maruya, Hiroh Saji, Shinsaku Imashuku
Journal: Blood (2004)
Combination Therapy with Lenalidomide, Bortezomib, Liposomal Doxorubicin and Dexamethasone (LBlipDD) May Overcome Resistance to Prior Treatment with Doxorubicin, Lenalidomide, and Bortezomib in High-Risk Multiple Myeloma (MM).
Authors: Reinhard Ruckser, Georg Tatzreiter, Elvira Kitzweger, Karin Strecker, Stefan Hraby, Veronika Buxhofer, Margarete Stampfl, Peter Kier, Karl H. Habertheuer, Milos Hejtman, Wolfgang Hinterberger
Journal: Blood (2007)
RTHP-18. LIQUID BIOPSY DISTINGUISHES RECURRENT GBM FROM RADIATION NECROSIS IN PERIPHARAL BLOOD OF PATIENTS WITH GBM
Authors: David Soler, Andrew Young, Kevin Cooper, Thomas McCormick, Andrew Sloan
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most aggressive and lethal type of brain cancer with a median survival of less than two years even with aggressive treatment. Among the many challenges in treating patients with this devastating disease is the ability to differentiate radiation induced change, often termed “radiation necrosis” from true GBM recurrence (rGBM). Radiation necrosis (RN) and GBM are very difficult to distinguish using standard Magnetic Resonance Imaging (MRI), and RANO criterion. Only a brain biopsy, an invasive procedure, can conclusively differentiate them. Recent studies by our group and others have demonstrated the presence of Myeloid-Derived Suppressor Cells (MDSC) in GBM. Here, we demonstrate the utility of a MDSC biomarker, Vanin-2 (VNN2), combined with expression of traditional MHC Class II molecule HLA-DR on CD14+ monocytes in GBM patients. Our preliminary data indicate that VNN2 expression on monocytic (CD14+)-MDSC (Mo-MDSC), in conjunction with CD14+ HLA-DRneg/low staining, can be used to monitor, among CD14+ monocytes, the frequency of circulating HLA-DRneg/low cells and VNN2+ cells whose ratio allow us to create an index (the DR-VNN Index or DVI) that can differentiate with high sensitivity and specificity, patients with recurrent GBM from phenotypically similar (on MRI) non-recurrent radiation necrosis (RN). Receiver-Operator Characteristic (ROC) curve analyses demonstrate an excellent level of sensitivity and specificity for the DVI (AUC=0.833, 95% CI (0.575, 1.0). This novel, quick, non-invasive and inexpensive “liquid biopsy” could replace invasive brain biopsy for differentiating rGBM from RN.
Cytokines' profiles to predict chemotherapy outcome in castration-resistant prostate cancer (CRPC).
Authors: K. L. Mahon, M. D. Chatfield, M. Lee-Ng, S. N. Breit, D. A. Brown, M. P. Molloy, G. M. Marx, N. Pavlakis, M. J. Boyer, M. R. Stockler, R. Wykes, S. M. Henshall, R. L. Sutherland, L. Horvath
Journal: Journal of Clinical Oncology (2011)

4598 Background: Chemotherapy improves symptoms and survival in advanced CRPC, however, ~50% of patients have chemoresistant disease. Early markers of chemoresistance will allow cessation of ineffective therapy and avoid toxicity. While MIC-1 and IL6 may be markers of response, comprehensive cytokine evaluation has not been performed. This study examined whether early changes in cytokine levels can predict chemoresistance and clinical outcome. Methods: Plasma/serum samples pre and post cycle 1 chemotherapy were collected from 59 men with metastatic CRPC (55 docetaxel, 7 mitoxantrone). Levels of 27 cytokines were measured using a bead-based immunoassay. MIC-1 levels were measured by ELISA. Patients were grouped as clinical responders (PR + SD) and nonresponders (PD) based on PSA response criteria (PD >25% PSA increase over treatment course if no PSA response). The associations between cytokine levels, response groups and overall survival (OS) were assessed by nonparametric tests and Cox regression survival analysis. Results: After one cycle of chemotherapy, nonresponders had significantly greater increases in 10 cytokines from baseline compared with those who responded to treatment (MIC-1 p=0.003; IL1ra p=0.004; IL1b p=0.01; IL4 p<0.001; IL5 p=0.041; IL6 p=0.003; IL7 p=0.009; IL8 p=0.017; IL12 p=0.004; IFNγ p=0.001). At a median survival of 15 months with 49 deaths, increases in IL8 (HR 2.4, 95% CI 1.1-5.0; p=0.02) and IFNγ (HR 2.6, 95% CI 1.3-5.2; p=0.009) levels by more than 40% from baseline after one chemotherapy cycle were associated with poorer OS. Higher baseline MIC-1 levels also predicted shorter OS (HR 1.6, 95% CI 1.3-2.0; p<0.0001). In a multivariate model including presence of visceral metastases (p=0.02), Gleason score (p=0.1), baseline ALP (p=0.2), baseline Hb (p=0.02) and baseline PSA (p=0.76), baseline MIC-1 levels were an independent predictor of survival (HR 2.0, 95% CI 1.3-3.1; p=0.002). Conclusions: Early changes in circulating levels of cytokines were associated with chemoresistance in men with CRPC. Additional associations between OS, baseline MIC-1 levels and changes in IL8 and IFNγ levels suggest inflammation influences outcomes in men with CRPC treated with chemotherapy.
High Cure Rates in Burkitt Leukemia and Lymphoma: NILG Study of the German Short Intensive Rituximab-Chemotherapy Program
Authors: Tamara Intermesoli, Alessandro Rambaldi, Chiara Cattaneo, Federica Delaini, Claudio Romani, Enrico Maria Pogliani, Chiara Pagani, Emanuele Angelucci, Elisabetta Terruzzi, Alessandro Levis, Vincenzo Cassibba, Daniele Mattei, Giacomo Gianfaldoni, Anna Maria Scattolin, Eros Di Bona, Elena Oldani, Margherita Parolini, Nicola Gokbuget, Dieter Hoelzer, Renato Bassan
Journal: Blood (2012)
193. Efficacy and Safety of Immunotherapy with Chimeric Antigen Receptor Targeting WT1 and HLA-A24:02 pMHC Complex
Authors: Hiroaki Ikeda, Yasushi Akahori, Yuki Orito, Yoshihiro Miyahara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Kazutoh Takesako, Hiroshi Fujiwara, Masaki Yasukawa, Hiroshi Shiku
Journal: Molecular Therapy (2016)

Recent success in the treatment of patients with B cell malignancy by CD19-CAR encourages the development of successive CAR therapy targeting broad range of tumor-associated antigens. However, the search for the appropriate target molecule for CAR, other than B cell markers, has not met the needs. The molecules recognized by CAR is generally limited to the cellular surface molecules, making difficult the search for the tumor-specific targets. Inspired by the physiological recognition of epitope peptide and MHC molecule (pMHC) by T cells, we have generated a series of antibodies that recognize the pMHC complexes with peptides derived from tumor antigens expressed intracellularly. Screening a phage display library of human antibody scFv, we isolated an scFv antibody clone "WT#213" that can specifically recognize WT1 p235-243 peptide (CMTWNQMNL) complexed with HLA-A24:02 molecule. We have constructed a retroviral vector that encodes the CAR consists of WT#213 and intracellular signal transduction domains of CD3ζ and GITR (WT#213 CAR). We confirmed the specific recognition of endogenous WT1-expressing cells by the CAR-T cells with the intracellular cytokine staining and the 51Cr release cytotoxic assay. Moreover, we demonstrated the effectiveness of adoptive cell therapy with WT#213 CAR against the WT1 expressing HLA-A24:02 positive human leukemia cells, utilizing NOG immunodeficient mice. To evaluate the safety of the WT#213 CAR, we predicted the potential property of WT#213 CAR to cross-react to normal tissues in humans. We conducted alanine scan analysis of WT1p235-243 peptide that was recognized by WT#213 CAR as well as the TCR derived from CTL clone TAK-1 which recognizes same epitope peptide in association with HLA-A24:02 to define the amino acids that were critically important in the recognition by the WT#213 CAR or TAK-1-derived TCR. After BLAST search, we synthesized the normal protein-derived peptides with potential risk of cross-reactivity, and tested the recognition of these peptides by WT#213 CAR or TAK-1-derived TCR. Although the critical peptides, and therefore the peptides with potential risk, were quite different between the WT#213 CAR and TAK-1-derived TCR, none of these peptides showed the stimulation of WT#213 CAR or TAK-1-derived TCR. The results here suggest that the immunotherapy with WT#213 CAR will be effective for the treatment of the leukemia patients without the predicted risk in the evaluation we performed.
307. Hitting the Kidney from All Angles: Using Direct Intrarenal Pelvis Injection Combined with Serotype and Promoter Targeting to Achieve Renal AAV Gene Delivery
Authors: Claire A. Schreiber, Sara Holditch, Yasuhiro Ikeda
Journal: Molecular Therapy (2016)

Using adeno-associated virus (AAV)-based gene therapy to treat renal diseases is an underdeveloped area. Renal anatomy and physiology make gene delivery to this organ especially difficult. Multiple AAV serotypes and routes of entry in rodents have been tried, with the majority of combinations targeting the renal tubules. To improve upon the current methods of AAV renal transduction for future use in the clinical setting, we employed direct intrarenal pelvis injections of AAV2, 6, 8 and 9 with the luciferase (Luc) or GFP transgene under the control of the cytomegalovirus (CMV) or putative kidney-specific promoters from myo-inositol oxygenase(MIOX), acyl-CoA synthetase medium-chain family member 2 (Acsm2), uromodulin (UMOD), kidney androgen-regulated protein (Kap) and solute carrier family 34 (sodium phosphate), member 1 (Slc34a1) mouse genes in C57Bl/6J mice. Renal luciferase transgene expression was strongest with AAV6, 8 and 9-CMV-Luc. AAV6 and 8-CMV-Luc resulted in stronger expression in the injected kidney, whereas AAV9-CMV-Luc showed equal, bilateral renal expression. AAV9 with the UMOD promoter gave the strongest and most highly renal-specific luciferase expression among all serotype and kidney promoter combinations. Using the GFP transgene we further established AAV transduction of multiple cell types in the kidney. AAV8-CMV-GFP transduced both glomerular and tubular renal cells, while AAV9-CMV-GFP most strikingly transduced periglomerular tubule cells. Both AAV8 and AAV9-UMOD-GFP solely transduced renal tubule cells. We are currently testing AAV variants isolated from clinical urine samples to determine their ability to transduce renal cells in vivo. Our results demonstrate efficient renal transduction by direct intrarenal pelvis injection of AAV vectors. Coupling specific renal cell tropisms of AAV serotypes and renal cell-type-specific promoters, along with the intrarenal pelvis injection strategy would pave the way for a renal-targeted AV gene therapy.
Response rate and treatment periods of vinorelbine ± trastuzumab for metastatic and recurrent breast cancers
Authors: Kazuhiro Shimada, Takashi Ishikawa, Kazuhito Tuchida, Satoshi Hasegawa, Kazutaka Narui, Tadao Fukushima, Takeshi Nakayama, Takeshi Sasaki, Yasushi Ichikawa, Itaru Endo
Journal: Annals of Oncology (2015)
PTH-080 Colon capsule endoscopy: does it have a role in routine clinical practice?
Authors: R Sidhu, D S Sanders, K Drew, M E McAlindon
Journal: Gut (2010)

<h3>Introduction</h3> The Pillcam Colon is a novel wireless and non-invasive modality to visualise the colon. This study evaluates the utility of Pillcolon in routine clinical practice and impact on patient management. <h3>Methods</h3> Patients were required to ingest laxatives according to the protocol. This consisted of 1.5-l Moviprep on the evening prior, 0.5-l on the morning of the procedure (09:00) followed by 20 mg domperidone (10:45) before swallowing the capsule (11:00). The patient had 45 ml Fleet phosphor-soda (DeWitt) at 13:00 and 30 ml (with 1 litre of water each time) at 17:00. A light snack was given at 18:00, followed by a bisacodyl suppository at 19:30 and patients were allowed home at 21:00. A 4-point grading scale was used to objectively describe the cleanliness of the colon (1=excellent, 2=good, 3=fair, 4=poor). Data were collected for all patients including demographics, indications, findings and subsequent change in management. <h3>Results</h3> Twenty-four examinations were performed in 23 patients: 19 females, mean age 45 years (range 16–84). The indications for Pillcolon included assessment of known inflammatory bowel disease (IBD, n=3), polyp surveillance (n=2) and blue rubber naevus syndrome (n=1). In 17 patients, Pillcolon was used to investigate the presence of IBD due to symptoms of altered bowel habit/pain (n=7), symptoms and the presence of anaemia/acute phase response or abnormal radiology (n=9) or with a family history (n=1). Pillcolon was chosen as a modality due to patient refusal to undergo standard colonoscopy (n=9), incomplete colonoscopy (n=11), physician choice (n=3) and unfit for colonoscopy (n=1). The capsule spent median of 81 min (20–424 min) in the small bowel and median of 168 min (0–547 min) in the colon. Ileum was seen in all and complete colon examination was achieved in 13 (54%) patients. The median cleanliness score was 2.5 (1–4) with a median reading time of 27 min (13–52 min). Findings included polyps (4), diverticulosis (3), colonic Crohn9s (3), small bowel Crohn9s (1), NSAID colopathy (1) and angioectasia (1). As a result of Pillcolon, 3 patients were treated for Crohn9s disease, 2 were referred for double balloon enteroscopy for histology and 3 patients were enrolled for polyp surveillance. Ten patients were discharged. NSAIDs was stopped in one patient and warfarin commenced in another (no contra-indication). <h3>Conclusion</h3> Pillcolon is a useful modality to investigate the colon, with a positive impact on patient management, particularly in patients who refuse or have failed colonoscopy. However comparisons with other standard modalities and further optimisation of bowel preparation are required, prior to advocating its use in routine practice.
Upfront Imatinib Therapy in CML Patients with Rapid Switching to Nilotinib for Failure to Achieve Molecular Targets or Intolerance Achieves High Overall Rates of Molecular Response and a Low Risk of Progression - An Update of the TIDEL-II Trial
Authors: David T. Yeung, Michael Osborn, Deborah L. White, Susan Branford, Michael Kornhauser, Cassandra Slader, Samar Issa, Devendra K Hiwase, Mark S. Hertzberg, Anthony P. Schwarer, Robin Filshie, Christopher K Arthur, Yiu Lam Kwan, Cecily J Forsyth, David Ross, Anthony K. Mills, Andrew Grigg, Timothy P. Hughes
Journal: Blood (2011)
Identification of Novel Antigens with Induced Immune Response in MGUS.
Authors: Simona Blotta, Hiroshi Yasui, Pierfrancesco Tassone, Roberto Bellucci, Yu-Tzu Tai, Rao Prabhala, Masood A. Shammas, Pierosandro Tagliaferri, Klaus Podar, Paola E. Neri, Mariateresa Fulciniti, Vidit Munshi, Dharminder Chauhan, Teru Hideshima, Salvatore Venuta, Jerome Ritz, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2006)
Alloimmunization To HLA Class I Antigens But Not H-Y Antigens Is Associated With Transfusion In Children With Sickle Cell Disease
Authors: Robert S. Nickel, Jeanne E. Hendrickson, Leslie S. Kean, Marianne E. McPherson Yee, Robert A. Bray, Howard M. Gebel, David B. Miklos, John T. Horan
Journal: Blood (2013)