tbuckley/cabot-search huggingface dataset:
Abstract 2223: Membranous expression of programmed cell death-ligand 1 (PDL1) on cancer cells is induced by cisplatin in an ATR dependent manner
Authors: Lea Schaaf, Meng Dong, Simon Heine, Heiko van der Kuip, Walter E. Aulitzky
Journal: Cancer Research (2016)

Abstract Cancer cells frequently develop strategies allowing to escape potential immune attacks by the host. One central component of this defense mechanism is the PDL1-PD1 axis with PDL1 expression on the surface of antigen presenting cells. DNA damaging chemotherapeutic are known to have suppressive effect on the immune system. Possible effects on immune checkpoints, however, are poorly understood. We investigated if Cisplatin, a widely used chemotherapeutic for treatment of ovarian and lung carcinomas, might influence expression of PDL1 on cancer cells of these pathologies. Treatment of cell lines as well as precision-cut tissue slices from patient tumors with clinically relevant dosages of cisplatin led to a significant induction of PDL1 protein in cancer cells as revealed by Western Blot and IHC analyses. This effect was independent on ATR or ATM activity since pre-treatment with ATR or ATM inhibitors had no significant effect on cisplatin induced total PDL1 protein levels. Interestingly, however, we observed an almost complete inhibition of cisplatin-induced membranous PDL1 upon ATR but not ATM inhibition as revealed by FACS analysis in unfixed cells. The role of the ATR axis was further corroborated by the finding that presentation of PDL1 at the cell surface was paralleled by phosphorylation of CHK1. Together our data indicate an important role of DNA damage induced ATR/CHK1 activity on the localization of PDL1 at the surface of cancer cells. These data implicate that combination of cisplatin with either anti-PD1 or anti-PDL1 antibodies or ATR/CHK1 inhibitors should reduce immunosuppressive mechanisms and enhance chemotherapy efficacy. Citation Format: Lea Schaaf, Meng Dong, Simon Heine, Heiko van der Kuip, Walter E. Aulitzky. Membranous expression of programmed cell death-ligand 1 (PDL1) on cancer cells is induced by cisplatin in an ATR dependent manner. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2223.
Treatment Outcome of Patients with Myelodysplastic Syndromes (MDS) in Regular Care: Incidence of IPSS Risk Groups and Different Therapies in the German Outpatient MDS Registry
Authors: H. Tilman Steinmetz, Isolde Böttger, Bernd Lathan, Annette Sauer, Enno Moorahrend, Kai Severin, Ulrich Germing, Stephan Schmitz, Norbert Gattermann
Journal: Blood (2014)
One in 10 young people experiences a distressing sexual problem
Authors: Jacqui Wise
Journal: BMJ (2016)

A sizeable minority of young people experience distressing sexual function problems but very few seek professional help, research published in the Journal of Adolescent Health has found.1

The third National Survey of Sexual Attitudes and Lifestyles included a nationally representative sample of 1875 sexually active and 517 sexually inactive participants aged 16-21 in the United Kingdom. The survey found that 34% of sexually active young men and 44% of sexually active young women had experienced sexual problems …
Monoclonal Gammopathy After Allogeneic Hematopoietic Stem Cell Transplant As a Marker For GvHD Onset
Authors: Federico Monaco, Francesco Zallio, Gioacchino Catania, Maria Teresa Corsetti, Lia Mele, Franco Dallavalle, Anna Baraldi, Flavia Salvi, Massimo Pini
Journal: Blood (2013)
Relative Impact of Psychosocial Factors, Comorbidities, and Disease Risk on the Utilization of Resources and Overall Outcome in Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Dawn S Speckhart, H. Kent Holland, Scott R. Solomon, Lawrence E. Morris, Asad Bashey, Leslie Kerns, Tina Berry, Karen Manion
Journal: Blood (2008)
Adherence to Hematologic Hold Parameters in Carboplatin and Dose-Dense Paclitaxel Chemotherapy for Ovarian Malignancies: A Survey of NCCN Member Institutions
Authors: Marina Stasenko, R Kevin Reynolds, Carolyn Johnston, Melissa Brackman, Karen McLean, Shitanshu Uppal
Journal: Journal of the National Comprehensive Cancer Network (2016)

To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers.This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically. Hematologic chemotherapy hold parameter values (absolute neutrophil count [ANC] and platelet count) on days 1, 8, and 15 of each cycle were queried. These hold parameters were compared with published data supporting the use of dose-dense chemotherapy regimens in ovarian cancer.The overall survey response rate was 85% (22/26 sites). Of responders, 27% (6 sites) were fully adherent with all hematologic hold parameters and 64% (14 sites) used hold parameters that differed from the published protocol. Specifically, all of these sites use hold parameters higher than those recommended in the literature. Two centers did not have center-specific hold parameters.Carboplatin and dose-dense paclitaxel chemotherapy has been shown to increase progression-free survival and overall survival in patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancers. However, our study found that two-thirds of queried sites had hold parameters higher than those in the published protocol. Using more stringent hold parameters may lead to compromised clinical outcomes. Further research is necessary to determine the optimal strategy to increase individual site adherence to chemotherapy hematologic hold parameters as specified in published trials.
Abstract 2994: Orlistat decreases endometrial cancer cell proliferation: implications for a novel treatment strategy
Authors: Weiya Z. Wysham, Dario R. Roque, Jianjun Han, Hui Guo, Lu Zhang, Paola A. Gehrig, Chunxiao Zhou, Victoria L. Bae-Jump
Journal: Cancer Research (2016)

Abstract Objectives: Fatty acid synthase (FAS) is a key enzyme involved in fatty acid synthesis. It also plays an important role in tumorigenesis and is highly expressed in many cancers, including endometrial cancer. Orlistat is a weight loss medication that has been shown to be a potent inhibitor of FAS. The goal of this study was to evaluate the anti-tumorigenic potential of orlistat in endometrial cancer cell lines. Methods: The endometrial cancer cell lines ECC-1 and KLE were treated with varying doses of orlistat (0.01-500 μM). Cell proliferation was assessed using the MTT assay. Cell cycle progression was evaluated by Cellometer and apoptosis was assessed using the Annexin V assay. Reactive oxygen species (ROS) was measured using the DCFH-DA assay. Western immunoblotting was performed to determine changes in FAS, cellular stress, cell cycle progression and the AMPK/mTOR pathways. Results: Orlistat inhibited cell proliferation in a dose-dependent manner in both cell lines (IC50 = 81.7 μM in ECC-1; IC50 = 145.5 μM in KLE). Treatment with orlistat resulted in G1 arrest but did not affect apoptosis. Orlistat increased ROS at high doses (500 uM, p = 0.008 for ECC-1 cells and p = 0.012 for KLE cells) and induced expression of BIP and PERK. Western immunoblot analysis demonstrated that orlistat decreased expression of FAS, acetyl-CoA carboxylase (ACC), and carnitine palmitoyltransferase 1A (CPT1A), important proteins in fatty acid metabolism. Treatment with orlistat also increased expression of phosphorylated AMPK and decreased expression of the downstream S6 protein. Conclusions: Orlistat suppressed cell growth in endometrial cancer cell lines through inhibition of fatty acid metabolism, induction of cell cycle G1 arrest, and modulation of the AMPK/mTOR pathway. Given that patients with endometrial cancer have high rates of obesity, orlistat should be further investigated as a novel strategy for endometrial cancer treatment and prevention. Citation Format: Weiya Z. Wysham, Dario R. Roque, Jianjun Han, Hui Guo, Lu Zhang, Paola A. Gehrig, Chunxiao Zhou, Victoria L. Bae-Jump. Orlistat decreases endometrial cancer cell proliferation: implications for a novel treatment strategy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2994.
A randomized trial (MA.17R) of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer.
Authors: Paul E. Goss, James N. Ingle, Kathleen I. Pritchard, Nicholas J. Robert, Hyman Muss, Julie Gralow, Karen A. Gelmon, Timothy Joseph Whelan, Kathrin Strasser-Weippl, Sheldon Rubin, Keren Sturtz, Antonio C. Wolff, Eric P. Winer, Clifford A. Hudis, Alison Stopeck, J. Thaddeus Beck, Judith Salmon Kaur, Kate Whelan, Dongsheng Tu, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2016)

LBA1 Background: Five years of aromatase inhibitor (AI) therapy either as up-front treatment or after 2-5 years of tamoxifen has become the standard of care for postmenopausal women with hormone receptor positive early breast cancer. Extending treatment with an AI to 10 years may further reduce the risk of breast cancer recurrence. Methods: We conducted a double-blind, placebo-controlled trial (Canadian Cancer Trials Group MA.17R) to test the efficacy of extending AI treatment for an additional five years using letrozole. The primary endpoint was disease-free survival. Results: A total of 1,918 women with early stage breast cancer were enrolled (median follow-up 75 months, 6.3 years). A total of 165 disease-free survival (DFS) events (67 on letrozole and 98 on placebo) occurred, of which 42 versus 53 were distant recurrences on letrozole and placebo, respectively. There were 200 deaths (100 in each treatment group). The 5 year DFS was respectively 95% for patients receiving letrozole versus 91% for those on placebo (HR 0.66; P = 0.01) from a two-sided log-rank test stratified by nodal status, prior adjuvant chemotherapy, interval between last dose of AI therapy and randomization, and duration of prior tamoxifen at randomization. The 5 year overall survival was respectively 93% for subjects on letrozole and 94% on placebo with a HR of 0.97 (P = 0.83). The annual incidence rate of contralateral breast cancer was 0.21% for subjects on letrozole versus 0.49% on placebo (P = 0.007). Conclusions: Compared to 5 years of AI treatment as initial therapy or preceded by 2-5 years of tamoxifen, extending AI treatment to 10 years significantly improves disease-free survival. Further analyses will provide a comprehensive picture of toxicities and QOL. Clinical trial information: NCT00754845.
Abstract 4685: Metformin enhances trastuzumab efficacy for HER2+gastric cancer cells
Authors: Jin-Soo Kim, Geum Ock Kim, Mi Young Kim
Journal: Cancer Research (2016)

Abstract Background: Trastuzumab is an effective monoclonal antibody against advanced gastric cancers (GCs) with HER2 amplification. Recently, HER2 directed therapies, such as pertuzumab or lapatinib are actively investigated in clinical trials, but showed disappointing results in patients with HER2+ GC. Unfortunately, the efficacy of trastuzumab is limited due to primary and acquired resistance to this agent. Metformin is a widely used antidiabetic drug and shows promising anti-tumor effect in several cancers. Material and Methods: The following GC cells were evaluated: HER2 amplification -positive (HER2+) and trastuzumab-sensitive NCI-N87 and OE19, HER2+ trastuzumab-resistant OE33 and HER2 negative AGS, H1750 and SNU601. We assessed response of these GC cells to trastuzumab alone or in combination with metformin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay and anchorage independent growth in soft agar. MGI (mean growth inhibition) was calculated by dividing the colony number of the treated group by that of the untreated control group. Western blots were performed to assess biochemical changes, especially those related with HER2 signaling components. Results: We observed that treatment with trastuzumab in combination with metformin induced a statistically significant decrease in the number of colonies formed in soft agar by N87 and OE19 cells, as compared to the numbers formed by control cells or cells in the single-treatment groups (Kruskal-Wallis test, p = 0.025, respectively). No growth inhibitory effect was detected in OE33 cells with Compared to trastuzumab alone, the combination of metformin resulted in decreased phosphorylation of HER2 and downstream targets, such as AKT or ERK, in trastuzumab-sensitive HER2+ cells. Conclusion: Collectively, these data support that trastuzumab and metformin are synergistic in trastuzumab-sensitive HER2+ GC cells. Combination effect on soft agar colony forming assaysCell LinesTrastuzumabMetforminCombinationIndexMGIPMGIPExpectedObservedPNCI-N870.8000.0210.8160.0310.6530.607&amp;lt;0.0011.077OE190.6000.0050.5650.0030.3390.152&amp;lt;0.0012.234OE330.9250.6770.8230.1030.7610.9000.4700.846 Citation Format: Jin-Soo Kim, Geum Ock Kim, Mi Young Kim. Metformin enhances trastuzumab efficacy for HER2+ gastric cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4685.
Use of imaging tests after primary treatment of thyroid cancer in the United States: population based retrospective cohort study evaluating death and recurrence
Authors: Mousumi Banerjee, Jaime L Wiebel, Cui Guo, Brittany Gay, Megan R Haymart
Journal: BMJ (2016)

To determine whether the use of imaging tests after primary treatment of differentiated thyroid cancer is associated with more treatment for recurrence and fewer deaths from the disease. Population based retrospective cohort study. Surveillance Epidemiology and End Results-Medicare database in the United States. 28 220 patients diagnosed with differentiated thyroid cancer between 1998 and 2011. The study cohort was followed up to 2013, with a median follow-up of 69 months. Treatment for recurrence of differentiated thyroid cancer (additional neck surgery, additional radioactive iodine treatment, or radiotherapy), and deaths due to differentiated thyroid cancer. We conducted propensity score analyses to assess the relation between imaging (neck ultrasound, radioiodine scanning, or positron emission tomography (PET) scanning) and treatment for recurrence (logistic model) and death (Cox proportional hazards model). From 1998 until 2011, we saw an increase in incident cancer (rate ratio 1.05, 95% confidence interval 1.05 to 1.06), imaging (1.13, 1.12 to 1.13), and treatment for recurrence (1.01, 1.01 to 1.02); the change in death rate was not significant. In multivariable analysis, use of neck ultrasounds increased the likelihood of additional surgery (odds ratio 2.30, 95% confidence interval 2.05 to 2.58) and additional radioactive iodine treatment (1.45, 1.26 to 1.69). Radioiodine scans were associated with additional surgery (odds ratio 3.39, 95% confidence interval 3.06 to 3.76), additional radioactive iodine treatment (17.83, 14.49 to 22.16), and radiotherapy (1.89, 1.71 to 2.10). Use of PET scans was associated with additional surgery (odds ratio 2.31, 95% confidence interval 2.09 to 2.55), additional radioactive iodine treatment (2.13, 1.89 to 2.40), and radiotherapy (4.98, 4.52 to 5.49). Use of neck ultrasounds or PET scans did not significantly affect disease specific survival (hazard ratio 1.14, 95% confidence interval 0.98 to 1.27, and 0.91, 0.77 to 1.07, respectively). However, radioiodine scans were associated with an improved disease specific survival (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82). The marked rise in use of imaging tests after primary treatment of differentiated thyroid cancer has been associated with an increased treatment for recurrence. However, with the exception of radioiodine scans in presumed iodine avid disease, this association has shown no clear improvement in disease specific survival. These findings emphasize the importance of curbing unnecessary imaging and tailoring imaging after primary treatment to patient risk.
Induced labour is not associated with risk of autism, say researchers
Authors: Jacqui Wise
Journal: BMJ (2016)

A nationwide sample of live births has found no association between induction of labour and autism.1 Writing in JAMA Pediatrics researchers said that the previously reported link between induced labour and autism was unlikely to be causal and should not factor in the clinical decision making process about whether to induce labour.

The growth in the reported prevalence …
Randomized phase III study of carboplatin plus S-1 compared with carboplatin plus paclitaxel as first-line chemotherapy in advanced non-small cell lung cancer (WJTOG3605).
Authors: H. Yoshioka, I. Okamoto, S. Morita, M. Ando, K. Takeda, T. Seto, N. Yamamoto, S. Nakamura, M. Fukuoka, K. Nakagawa
Journal: Journal of Clinical Oncology (2010)

7530 Background: S-1 is an oral fluorinated pyrimidine formulation that combines tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate in a molar ratio of 1:0.4:1. Phase II studies of S-1 plus platinum compounds have shown activity for first-line treatment of advanced NSCLC. Methods: Chemotherapy-naïve patients (pts) with advanced stage (IIIB/ IV) NSCLC, ECOG PS of 0-1, and adequate organ functions were randomly assigned to receive either carboplatin AUC 5 mg/ml/min on day 1 plus oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 14 or carboplatin AUC 6 mg/mL/min plus paclitaxel (200 mg/m2) on day 1 every 21 days. The primary endpoint was to compare overall survival (OS) to demonstrate noninferiority for carboplatin/S-1 relative to carboplatin/paclitaxel (upper CI limit for HR < 1.33); secondary endpoints included progression-free survival (PFS), response rate, safety, and quality of life. Results: A total of 563 eligible patients were enrolled from August 2006 to May 2008. Demographic factors were well balanced. At the interim analysis, with 61% of the expected number of events available, the study passed the O'Brien-Fleming boundary at 0.006 for positive results and noninferiority of carboplatin/S-1 compared with carboplatin/paclitaxel was confirmed for OS (hazard ratio [HR], 0.928; 95% CI, 0.730 to 1.179, median survival 15.3 vs 13.3 months). There was no significant difference in PFS between the two treatment arms. For carboplatin/S-1, rates of grade 3 or 4 leukopenia, neutropenia, and febrile neutropenia (p < 0.001) were significantly lower, whereas grade 3 or 4 thrombocytopenia (p < 0.001) was more common. For nonhematologic toxicities, alopecia, neuropathy and arthralgia occurred less frequently (p < 0.001) in the carboplatin/S-1 group. Significantly more pts in carboplatin/S-1 demonstrated clinically relevant favorable neurotoxicity (Ntx) profile (p < 0.001), as assessed by the 11-item FACT/GOG-Ntx subscale. Conclusions: Oral S-1 with carboplatin provides similar efficacy with better tolerability and more convenient administration than carboplatin/paclitaxel as a first-line treatment for advanced NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Taiho Pharmaceutical
Adenovirus Vector E4 Gene Promotes Angiogenesis through Modulation of Junctional Connexin 40 and 43 Expression.
Authors: Joseph Cheng, Fan Zhang, George Lam, Neil R. Hackett, Shiyang Wang, Hideki Amano, Sergey V. Shmelkov, Lauren M. Young, Barbara Hempstead, Ronald G. Crystal, Shahin Rafii
Journal: Blood (2004)
A major outbreak of conjunctivitis caused by coxsackievirus A24, Réunion, January to April 2015
Authors: Nadège Marguerite, Elise Brottet, Frédéric Pagès, Marie Christine Jaffar-Bandjee, Isabelle Schuffenecker, Laurence Josset, Pascal Vilain, Laurent Filleul
Journal: Eurosurveillance (2016)

From January to April 2015, Réunion experienced a major outbreak of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24, which heavily impacted the healthcare system. According to the general practitioners' (GP) sentinel network, the number of medical consultations due to conjunctivitis during this period was estimated at ca 100,000. This report describes the characteristics of the outbreak, which were obtained through several different yet complementary surveillance systems on the island. These included the network of hospital emergency departments (OSCOUR network), the GPs' sentinel network, an Internet-based population cohort ('Koman i lé') participating in a survey on distinct symptoms including 'red eyes' and the monitoring of eye drop sales. Overall the results of the different surveillance approaches were in good agreement regarding the outbreak dynamic. A peak of patients with conjunctivitis was detected in the first 15 days of March (week 10 and 11), coinciding with increased eye drop sales on the island. Strains recovered from outbreak cases belonged to genotype IV and were most closely related to strains identified in AHC outbreaks in China, Egypt and Japan since 2010. Continued surveillance of AHC in Réunion remains important not only locally, but also because frequent exchanges between the island and mainland France may lead to introduction of this virus in Europe.
The "Diana effect"
Authors: R. Morgan-Jones, K. Smith, P. Oakley, C. Berry, C. Mulholland, M. Stevenson, P. Reilly, J. R Mitchell
Journal: BMJ (1998)

Editor—The death of Diana, Princess of Wales has been followed by an unprecedented public and media response. Shevlin et al showed that her death and subsequent funeral have had a profound psychological impact on the public.1 Furthermore, many people have consulted their general practitioners for depression linked to the princess’s death.2

It is therefore perhaps surprising that in contrast to the increased number of consultations for psychological problems the number of admissions for trauma at the North Staffordshire Royal Infirmary has fallen by 10% since Diana’s death. Perhaps more poignantly (figure) the number of admissions of patients with injuries greater than 15 on the injury severity score has fallen. This trend continued for three months; only in December did numbers start to return to previous values. Most of the patients are injured in road traffic accidents, and it would be tempting to imply a causal—albeit probably subliminal—association with driving habits after the tragic events in Paris. 

It is too soon to judge whether the tragic manner of Princess Diana’s death will have a lasting impact on admissions for trauma, but we would be interested to know whether other centres have experienced a similar fall in the number of acute and severely injured patients.