tbuckley/cabot-search huggingface dataset:
A phase I/II study of oncolytic reovirus plus carboplatin/paclitaxel in patients with advanced solid cancers with emphasis on squamous cell carcinoma of the head and neck (SCCHN).
Authors: E. M. Karapanagiotou, J. D. Chester, H. S. Pandha, G. M. Gill, M. C. Coffey, K. Mettinger, K. J. Harrington
Journal: Journal of Clinical Oncology (2010)

3080 Background: Reolysin is an isolate of reovirus, a RNA virus which replicates in cells with activated Ras signaling pathway while sparing normal cells. We conducted a phase I/II dose escalation study of intravenous Reolysin in combination with chemotherapy. The study has completed enrollment. Methods: Reolysin was administered to cohorts of 3 patients in escalating doses (3x109, 1x1010, 3x1010 TCID50) on days 1-5 while carboplatin AUC 5 and paclitaxel 175 mg/m2 were administered on day 1 of a 3-weekly schedule. Eligible patients had good performance status (ECOG PS: 0-2) with advanced cancers which were not amenable to curative treatment or were refractory to standard therapy for which paclitaxel/carboplatin was appropriate palliative chemotherapy. Results: Thirty-one patients (24 males; median age 59 years) with head and neck cancer (n=24), melanoma (n=4), peritoneal/endometrial cancer (n=2) or sarcoma (n=1) received 147 cycles (median 5, range 1-8) of treatment. In the dose-escalation phase of the study, there were no dose-limiting toxicities. Grade 3/4 toxicities included anaemia, leucopenia, neutropenia, lymphopenia, thrombocytopenia, infection and hypotension. Neutralising anti-reovirus antibody responses will be presented. In the phase 1 study, partial responses (PR) were noted in 2 of 5 patients with head and neck cancer. The Phase 2 study treated head and neck cancer patients at the maximum dose level (3 × 1010 TCID50) in order to further assess tumour response. In total, 19 patients with head and neck cancer received at least 2 cycles and are evaluable for response. Most were SCCHN refractory to previous platinum-based chemotherapy for recurrent/metastatic disease. PR was seen in 8 patients (42%) and SD in 6 (32%). One additional PR and 1 SD were observed among 4 patients with malignant melanoma. Final results for median OS and PFS will be presented. Conclusions: Intravenous administration of reovirus in combination with carboplatin/paclitaxel is a safe and well-tolerated combination with promising anticancer activity in SCCHN. Further evaluation of this combination in a randomized phase III trial in SCCHN is underway. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncolytics Biotech Oncolytics Biotech Oncolytics Biotech Oncolytics Biotech Oncolytics Biotech
Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients
Authors: Gang Hu, Pekka Jousilahti, Jaakko Tuomilehto
Journal: Diabetes Care (2007)

We appreciate Dr. Talim's comments (1) on the results of our study (2) on type 2 diabetes and the risk of Parkinson's disease. We agree that polyunsaturated rich vegetable oils may be associated with the risk of both type 2 diabetes and Parkinson's disease. In …
Soundings: A painful experience
Authors: Liam Farrell
Journal: BMJ (2002)

I was on an Airtours flight from Florida recently when medical assistance was called for. The patient had benign prostatic hyperplasia and was in retention. Since we had another seven hours to fly, holding on was not an option. He needed a catheter, so I was reassured that the plane's inventory of medical equipment included catheters and collecting bags. But I then found that there was no lignocaine gel, no lubricating jelly, and no gloves.

Performing a catheterisation without gloves or anaesthetic was not pleasant, but the lack of lubricating jelly proved a bridge too far, so when the patient started screaming I deputised some antiseptic cream as an ersatz lubricant.

As the catheter was non-retaining, I advised the greatly relieved patient not to drink any fluids for the rest of the flight and to attend accident and emergency on his way home. I then had to remain on alert for the next seven hours. Before disembarking I was asked to sign a form indemnifying Airtours against any claim arising from the procedure and was offered a bottle of wine as a gesture of appreciation.

I had expressed my concerns to the steward, but having heard nothing after a few weeks I contacted Airtours. The company's flight officer explained that Airtours usually received inflight medical advice from an institute in the United States and the airline's medical officer assured me that gloves had been present in the equipment box—I just hadn't found them. He said that he had done hundreds of catheterisations and had never used lignocaine gel. In a subsequent letter, he insisted that the company's equipment was standard to all airlines, and that “the catheters are self lubricating, and being small and atraumatic do not need lubrication or local anaesthetic.” Really?

As a doctor, I had no choice but to respond to the patient's needs, and without that choice I was forced to perform a difficult procedure with inadequate equipment. The poverty of the Airtours response was depressing, especially considering how much money I had saved the company; if a doctor hadn't just happened to be on board, the plane would have had to return to Florida. Maybe in future Airtours should take one fewer passenger and a bit more equipment, and maybe omit those magical self lubricating catheters. I won't be travelling with Airtours again—not without taking my own lubricating jelly.
A novel leukemia cell line, MR-87, with positive Philadelphia chromosome and negative breakpoint cluster region rearrangement coexpressing myeloid and early B-cell markers
Authors: J Okamura, S Yamada, E Ishii, T Hara, H Takahira, J Nishimura, K Yumura, K Kawa- Ha, K Takase, Y Enomoto
Journal: Blood (1988)
Cellular Intrinsic Mechanism Affecting The Outcome Of AML Treatment With Ara-C In a Syngeneic Mouse Model
Authors: Zheng Chen, Dongming Tan, Wenjun Zhao, Guangsong Su, Yanwen Zheng, Chao He, Miechaleen D Diers, Zhengwei Mao, Timothy Singleton, David A. Largaespada, Bin Yin
Journal: Blood (2013)
The importance of mindfulness in psychosocial distress and quality of life in dermatology patients
Authors: K. Montgomery, P. Norman, A.G. Messenger, A.R. Thompson
Journal: British Journal of Dermatology (2016)

Mindfulness, defined as purposively and nonjudgementally paying attention in the present moment, could be used within psychosocial interventions to reduce the distress associated with social anxiety and avoidance found in many skin conditions. However, little is known about the relationship between naturally occurring levels of mindfulness and distress in dermatology patients.To examine the relationship between mindfulness and psychosocial distress in a dermatological population. It was hypothesized that higher levels of mindfulness would be associated with lower levels of social anxiety, anxiety, depression and skin shame, and with better quality of life.Adult dermatology outpatients (n = 120) from one hospital completed items assessing subjective severity, skin shame, fear of negative evaluation, anxiety and depression, quality of life, and levels of mindfulness.Considering depression, 14% reported mild, 5% moderate and 2·5% severe symptoms. For anxiety, 22% reported mild, 23% moderate and 6% severe symptoms. In addition, 33·4% reported clinically significant social anxiety. After controlling for subjective severity, mindfulness explained an additional 19% of the variance in depression, 39% in anxiety, 41% in social anxiety, 13% in skin shame and 6% in dermatological quality of life. One specific facet of mindfulness (acting with awareness) was found to be the most consistent predictor of distress.The findings indicate that higher levels of mindfulness are associated with lower distress. This suggests that facilitating mindfulness may be helpful in reducing distress in dermatology patients, and the use of mindfulness techniques warrants further investigation.
Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis
Authors: Qian Wang, Shuai Ma, Nan Song, Xin Li, Ling Liu, Shangda Yang, Xiang Ding, Lin Shan, Xing Zhou, Dongxue Su, Yue Wang, Qi Zhang, Xinhua Liu, Na Yu, Kai Zhang, Yongfeng Shang, Zhi Yao, Lei Shi
Journal: Journal of Clinical Investigation (2016)

The histone demethylase PHF8 has been implicated in multiple pathological disorders, including X-linked mental retardation and tumorigenesis. However, it is not clear how the abundance and function of PHF8 are regulated. Here, we report that PHF8 physically associates with the deubiquitinase USP7. Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation. The USP7-encoding gene was also transcriptionally regulated by PHF8, via positive feedback. USP7 was overexpressed in breast carcinomas, and the level of expression positively correlated with expression of PHF8 and cyclin A2 and with the histological grade of breast cancer. We showed that USP7 promotes breast carcinogenesis by stabilizing PHF8 and upregulating cyclin A2 and that the interaction between USP7 and PHF8 is augmented during DNA damage. Moreover, USP7-promoted PHF8 stabilization conferred cellular resistance to genotoxic insults and was required for the recruitment of BLM and KU70, which are both essential for DNA double-strand break repair. Our study mechanistically links USP7 to epigenetic regulation and DNA repair. Moreover, these data support the pursuit of USP7 and PHF8 as potential targets for breast cancer intervention, especially in combination with chemo- or radiotherapies.
Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10) [see comments]
Authors: P Herve, J Wijdenes, JP Bergerat, P Bordigoni, N Milpied, JY Cahn, C Clement, R Beliard, B Morel-Fourrier, E Racadot
Journal: Blood (1990)
Abstract 13427: Radial Versus Femoral Access for Primary Percutaneous Coronary Intervention: Single Center Study of 928 Consecutive Patients
Authors: Refai Showkathali, Pille Harding, John Davies, Kare Tang, Rohan Jagathesan, Jeremy Sayer, Gerald Clesham, Paul Kelly, Rajesh Aggarwal
Journal: Circulation (2011)
PTH-091 Measurement of tnf-alpha drug levels and free versus total anti-drug antibodies using three commercially available assays: Abstract PTH-091 Table 1
Authors: Z Arkir, N Unsworth, BD Warner, G Richards, PM Irving
Journal: Gut (2015)

<h3>Introduction</h3> Commercial assays are now available for therapeutic drug monitoring (TDM) of anti-TNF drugs and antibodies (ADAb). Utility of free versus total ADAb assays remains debatable, further complicated by lack of assay standardisation. Here we report analytical comparison of 3 commercially available assays for Infliximab (IFX) and Adalimumab (ADAL) drug levels (DL) and ADAb. <h3>Method</h3> Prospective evaluation of IFX and ADAL DL and ADAb was performed using our local LISA-TRACKER (LT) assay automated on e-Robot in IBD patients. Samples were also analysed by Immundiagnostik (IM, Germany) and Promonitor (PM, Spain) ELISA automated on Grifols Triturus. LT and PM utilises a specific bridging ELISA to quantitatively measure free-ADAb whereas IM utilises a dissociation step to enable detection of total-ADAb generating semi-quantitative results. IFX assays measure free drug but differ in microtitre plate coating and secondary detection reagents. Data was analysed using Passing Bablok and bias plots. LT and PM kits were provided at no cost. <h3>Results</h3> Summary of DL comparisons shown below: Samples analysed in different batches showed different kit biases against each other for IFX. Batch 1 showed that LT assay had 43.9% positive bias against ID kit whereas batch 2 demonstrated –26% negative bias. Both LT and ID kits used had different lot numbers. This change in bias was not observed in ADAL assays which showed consistent and systematic bias. PM kit showed concentration dependent bias changes within the same assay. 4 patients tested (n = 79) IFX ADAb positive with undectable DL with one exception where total/free ADAb was negative using ID and PM assays. A further 17 patients tested total ADAb positive using IM with detectable DL (0.5–9.2 ug/mL). 1 patient tested ADAL ADAb positive using LT, PM and ID assays however ID and PM assays produced positive resuts on a further 4 specimens, all with ADAL DL &gt;5 ug/mL. <h3>Conclusion</h3> Although commercial assays are now available, our data highlights the need for assay standardisation. Free ADAb assays were in agreement however ADAb positivity was higher using ID assay. Significance of total ADAb positivity is unknown. Results for both IFX and ADAL confirm that DL are not transferable from one assay to another and as such, common therapeutic cut-offs will not be applicable. Further work is warranted to establish the cause of batch-to-batch variation observed. <h3>Disclosure of interest</h3> Z. Arkir: None Declared, N. Unsworth: None Declared, B. Warner: None Declared, G. Richards: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.
Silent dissemination of colistin-resistant Escherichia coli in South America could contribute to the global spread of the mcr-1 gene
Authors: Miriam R Fernandes, Quezia Moura, Luciana Sartori, Ketrin C Silva, Marcos PV Cunha, Fernanda Esposito, Ralf Lopes, Luciana K Otutumi, Daniela D Gonçalves, Milena Dropa, Maria H Matté, Daniel FM Monte, Mariza Landgraf, Gabriela R Francisco, Maria FC Bueno, Doroti de Oliveira Garcia, Terezinha Knöbl, Andrea M Moreno, Nilton Lincopan
Journal: Eurosurveillance (2016)

During a Brazilian multicentric antimicrobial resistance surveillance study, colistin resistance was investigated in 4,620 Enterobacteriaceae isolated from human, animal, food and environmental samples collected from 2000 to 2016. We present evidence that mcr-1-positive Escherichia coli has been emerging in South America since at least 2012, supporting a previous report on the possible acquisition of mcr-1-harbouring E. coli by European travellers visiting Latin American countries.
PRL-3 Mediates Survival of Primary Myeloma Cells
Authors: Torstein Baade Rø, Tobias Schmidt Slordahl, Pegah Abdollahi, Esten Vansemb, Lars Hagen, Katarzyna Anna Baranowska, Kristine Misund, Geir Slupphaug, Magne Borset
Journal: Blood (2014)
A 65 year old man with macroscopic haematuria and acute kidney injury
Authors: Richard Germann, Kannaiyan Rabindranath, Daniel Ninin, Peter Sizeland
Journal: BMJ (2016)

A 65 year old man who presented to his general practitioner with a three day history of bright red, painless, macroscopic haematuria was found to have a raised serum creatinine of 461 μmol/L (reference range 60-105) (estimated glomerular filtration rate 11 mL/min/1.73 m2). His baseline serum creatinine had been stable (~120 μmol/L) for five years until one month earlier, when he had an episode of acute kidney injury while in hospital for cellulitis of the right leg. After discharge the cellulitis had resolved but his serum creatinine had remained raised at 252 μmol/L. He denied any recent respiratory infections, weight loss, night sweats, lethargy, or haematuria.

His medical history included hypertension, type 2 diabetes, chronic kidney disease stage 3, coronary artery bypass grafting, atrial fibrillation, an ischaemic stroke, benign prostatic hypertrophy, and tobacco use. His regular drugs (all once daily) were digoxin 125 μg, atorvastatin 80 mg, tamsulosin 400 μg, metoprolol 95 mg, aspirin 100 mg, and warfarin.

On physical examination his blood pressure was 116/70 mm Hg and he had mild pedal oedema. Urine analysis showed gross haematuria and proteinuria (protein:creatinine ratio 51.2 mg/mmol; reference <23).

His international normalised ratio (INR) was raised, at 5.7.

He was referred urgently to hospital, where a renal ultrasound showed normal sized kidneys with no hydronephrosis. Antinuclear antibodies and antibodies to hepatitis B, hepatitis C, and HIV were all negative. Complement factors C3 and C4, serum electrophoresis, and serum free light chains levels were all unremarkable.

In the absence of an anti-neutrophil cytoplasmic antibody result, which was subsequently reported as negative, he was given 1 g of intravenous methylprednisolone as empirical treatment for a possible vasculitis. Prothrombin X and 10 mg of intravenous vitamin K were also given to correct the clotting defect and facilitate kidney biopsy (fig 1⇓).



Fig …
Carcinogenicity of 3-Methyl-2-naphthylamlne and 3,2′-Dimethyl-4-aminobiphenyl to the Bladder and Gastrointestinal Tract of the Syrian Golden Hamster With Atypical Proliferative Enteritis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Gary M. Williams, Visalam Chandrasekaran, Shoiochi Katayama, John H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1981)

3,2'-Dimethyl-4-aminobiphenyl (DMAB) and 3-methyl-2-naphthylamine (MeNA) were each administered to groups of 25 male noninbred Syrian golden hamster weanlings in doses of 100 mg/kg body weight by weekly sc injections for a total of 38 injections over 18--22 months. DMAB produced a high incidence of urinary bladder epithelial neoplasms and intestinal neoplasms. Other neoplasms included squamous papilloma of nonglandular stomach, lymphoma-leukemias, and squamous cell carcinomas of the ear duct and skin. With MeNA, urinary bladder epithelial neoplasms occurred but no intestinal tumors. Also present were soft-tissue sarcomas at the injection site, papilloma of forestomach, and lymphoma-leukemias. Most hamsters in both groups as well as the control group had a chronic form of atypical proliferative enteritis that affected the small or large intestine. The occurrence of intestinal tumors with DMAB could be related to sensitizing effect of increased intestinal mucosal proliferation. Apart from this effect, hamsters displayed a distinct susceptibility to bladder carcinogenesis by these aromatic amines.
Recombinant targeted toxin based on HER2-specific DARPin possesses a strong selective cytotoxic effect in vitro and a potent antitumor activity in vivo
Authors: Evgeniya Sokolova, Galina Proshkina, Olga Kutova, Olga Shilova, Anastasiya Ryabova, Alexey Schulga, Oleg Stremovskiy, Tatiana Zdobnova, Irina Balalaeva, Sergey Deyev
Journal: Journal of Controlled Release (2016)
Prognostic analysis of gastrointestinal stromal tumor by mitotic activity, size of tumor and mutational type of C-Kit protein
Authors: J. Kim, M. Lim, I. Kim, H.-S. Lee, S. Choi, M. H. Lee, Y. S. Hur, S. H. Shin, E. K. Cho, C. S. Kim, Z.-H. Woo
Journal: Journal of Clinical Oncology (2005)

9046 Background: GIST is the most common mesenchymal tumor of the gastrointestinal tract. Methods: 53 GIST patients, underwent grossly total mass resection in Inha University Hospital, Incheon, Korea from March 1997 to March 2004, were included in this study. The median follow-up period was 34 months. The evaluation of C-kit mutation on exon 11 was performed. Three-year recurrence free survival rate and 3-year overall survival rate have been analyzed. Results: The median value of mass size was 6 Cm(range, 0.8Cm - 20Cm). The most common primary site was stomach with 30 cases(56%), followed by small bowel with 11 cases, large bowel with 6 cases and peritoneal dissemination with 6 cases. Twenty-one patients had disease recurred during follow-up period which marked recurrence rate with 39%. The rates of 3-year recurrence free survival and 3-year overall survival were 50% and 76%, respectively. Three-year recurrence free survival rate of patients with less then 10 mitotic activity under 50 HPF was 79%, whereas the rate of patients with more than 10 mitotic activity under 50 HPF was 30%(p=0.026). Three-year overall survival rates of patients with less than 10 mitotic activity and that of patients with more than 10 mitotic activity were 90% and 64%, respectively(p=0.0368). Three-year recurrence free survival rate of patients with tumor size less than 5 Cm was 77% and the rate of patients with tumor size greater than 5 Cm was 33%(p=0.0006). The 3-year overall survival rates of patients with tumor size less than 5Cm and that of patients of tumor size greater than 5Cm were 86% and 66%, respectively(p=0.023). The study on mutational type of C-kit protein showed missence exon 11 mutation with 4 cases(7%) and deletion/insertion exon 11 mutation with 24 cases(45%). Three-year recurrence free survival rate of deletion/insertion exon 11 found to be 35% as the rate of rest patients was 64% and the difference between these two groups showed statistical significance.(p=0.0383). Conclusions: This study showed that mass size and mitotic activity were important prognostic factors in GIST. Delete/Insert gene mutation on exon 11 was found to be poor prognostic factor. No significant financial relationships to disclose.
Circulating tumor cells (CTCs) in peripheral blood of primary breast cancer patients
Authors: B. K. Rack, C. Schindlbeck, S. Hofmann, A. Schneeweiss, M. Rezai, M. Beckmann, K. Pantel, A. Schneider, H. Sommer, W. Janni
Journal: Journal of Clinical Oncology (2007)

10595 Background: Detection of CTCs has been shown to predict decreased PFS and OAS in metastatic breast cancer, whereas only limited data has been published in the adjuvant setting. We evaluate the role of CTCs in peripheral blood at primary diagnosis and during adjuvant chemotherapy, endocrine and bisphophonate treatment within the SUCCESS-Trial (n=3,658 pts). Methods: We analyzed 23ml of peripheral blood from 1767 N+ and high risk N- primary breast cancer pts before systemic treatment. 852 of these pts have undergone follow-up blood sampling after completion of chemotherapy. The presence of CTCs was assessed with the CellSearchSystem (Veridex, Warren, USA). Briefly, after immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish epithelial cells and leukocytes. Results: 10% of pts with a blood sampling before systemic treatment (n=170) showed &gt;1CTC before the start of systemic treatment (mean 13, range 2–827). While we found 2 CTCs in 5% of pts, 3% had 3–5 CTCs and 1% 6–10 and &gt;10 CTCs each. The presence of CTCs did not correlate with tumor size (p=.07), grading (p=.30), hormonal status (p=.54) or Her2-Status of the primary tumor (p=.26). However, we observed a significant correlation with the presence of lymph node metastases (p=.015). None of 24 healthy individuals showed more than 1 CTC. Among those 852 pts with follow-up blood sampling after the completion of cytostatic treatment, 11% were CTC positive before starting systemic treatment (mean 7, range 2–166), while 7% of patients presented with &gt;1CTC after completion of chemotherapy (mean 6, range 2–84). Of those, initially CTC positive, 10% remained positive (n=9) and 90% had a negative CTC test after chemotherapy (n=82). Of those initially CTC negative, 93% remained negative (n=711), whereas 7% returned with a positive CTC test (n=50) (p=.24). Conclusions: Our data show good feasibility of this highly standardized and easily applicable approach for the detection of CTCs in a large number of primary breast cancer patients. In a considerable number of patients, persistent CTCs can be detected after completion of cytostatic treatment. Whether this finding is prognostically relevant will have to been shown with longer follow-up of the SUCCESS-trial. No significant financial relationships to disclose.