tbuckley/cabot-search huggingface dataset:
SHADOW study: Comparison of conventional clinical follow-up with clinician led video follow-up in newly diagnosed patients with intermediate and high grade glioma receiving adjuvant temozolomide therapy.
Authors: Vijay Maruti Patil, Nikhil Pande, Arun Chandrasekharan, Raees Tonse, Chandrakanth MV, Rahul Krishnatry, Shamika Ghanekar, Nazia Bano, Jayant Sastri, Tejpal Gupta, Rakesh Jalali
Journal: Journal of Clinical Oncology (2017)

2024 Background: In patients with gliomas, nurse led telephonic follow-up was associated with high satisfaction rates and was a valid alternative approach to conventional hospital based follow-up. However, other alternative forms of follow-up have not been studied in patients on active treatment. Methods: SHADOW was a prospective, randomized trial (CTRI/2017/01/007626). Adult intermediate to high grade glioma patients on adjuvant temozolomide with facilities for live video call were invited. After their consent, patients underwent a video follow-up (VF) 4 days prior to clinical follow-up (CF). The decisions taken during the VF and CF were noted in 5 domains, relating to temozolomide decisions (primary endpoint), concurrent medications, need for imaging, molecular testing and rehabilitation. Clinicians performing VF or CF were randomly assigned and were blinded for the other arm decisions. Patients satisfaction and costs incurred in each type of follow-up was documented. The planned sample size was 65, assuming an alpha of 0.05, a kappa coefficient of 0.9 with a one sided CI for lower limit of 0.6 and assuming a 20% lost to follow up rate. Agreement analysis was performed for calculation of Cohen's kappa coefficient. Results: 112 patients were screened and 65 were accrued. All patients underwent both VF and CCF. The concurrence in decision of administering temozolomide between VF and CCF was 100% (Cohen kappa = 1.0, 95%CI 1.0-1.0, p &lt; 0.00). In concurrent medication domain (k = 0.66,95% CI 0.04 -1, p &lt; 0.00), imaging domain (k = 1.0, 95%CI 1.0-1.0, p &lt; 0.00), rehabilitation domain (k = 1.0, 95%CI 1.0-1.0, p &lt; 0.00) and molecular testing domain (k = 0.65, 95% CI 0.20-1, p &lt; 0.00), the agreement was substantial. The satisfaction rate was 100% post video follow up and was 98.5 % post clinical follow up. The median cost incurred in VF was 58.15 USD (IQR 43.38-91.69) while that incurred in CCF was 131.23 USD (IQR 68.8-256 (p &lt; 0.00)). Conclusions: The decisions taken regarding administration of adjuvant TMZ were similar between VF and CCF. Hence, it's practical and economical to substitute CCF with VF during adjuvant TMZ administration. Clinical trial information: CTRI/2017/01/007626.
Scalp-cooling achieved by cold-cap therapy efficacy in reducing the risk of alopecia in women with breast cancer receiving chemotherapy.
Authors: Niraj K. Gupta, Erica Giblin, Christopher Leagre, Sarah Longmire-cook, Robert Paul, Thomas Tigges, Robert Liebross, Erin McCammack, Julia Compton, Sue Ann Gilroy, Fuad Hammoudeh, Thomas Schmidt
Journal: Journal of Clinical Oncology (2016)

e12521 Background: Alopecia is a common and distressing side-effect endured by breast cancer patients recieving chemotherapy. Scalp-cooling methods have been reported to decrease the incidence of alopecia with chemotherapy without negatively affecting the outcomes.We report our experience using cold-cap therapy to achieve scalp-cooling in breast cancer patients treated with chemotherapy at our center. Methods: Cold-Cap therapy was offered to breast cancer patients to be treated with neo-adjuvant/adjuvant chemotherapy. Many patients declined it due to financial reasons. Cold-caps from different companies were used and were applied to the scalp during the administration of chemotherapy according to the included-instructions. Hair loss was assessed at every cycle and was graded according to the criteria described by Dean et al. Results: Sixteen ladies used the cold-cap therapy between 1/04/2015 and 1/10/2016. Median age was 44 years, range 34-69 years. Fourteen ladies were caucasians, 1 african-american and 1 from the middle-east. Nine ladies (56%) had neoadjuavnt and 7(46%) had adjuvant chemotherapy. The regimens used were; dose-dense ACT (4), TCH (3), Perjeta +Herceptin+taxotere (3), Perjeta +TCH (4) and TC (3). All ladies completed the planned number of cycles. Only one lady had complete hair loss (Gde- 3 pts (18%) had ( Grade-0) no hair loss. Seven (46%) had Gde-1, 0-25% hairloss, 4 pts (25%) had Gde-2,25-50% hairloss, and 1 pt (6%) had Gde-3,50-75% hairloss and only 1(6%) had complete hairloss, Gde-4, > 75% hairloss. The lady with complete hairloss had receieved dose-dense ACT and was from the middle-east. Cold-cap treatments were tolerated well and mild burning on the scalp and headaches were the commonest complaints in a few patients. None of them discontinued the cold-cap therapy. Conclusions: Cold-cap therapy is an effective and well tolerated method to prevent alopecia in ladies with breast cancer receiving various chemotherapy regimens.
Flooding-related displacement and mental health
Authors: Shilu Tong
Journal: The Lancet Planetary Health (2017)

In the past decade, flooding took place in 50 of 53 countries in the WHO European region, with the most severe floods in Romania, Russia, Turkey, and the UK.1 It is projected that flooding could affect 250 000–400 000 additional people across Europe by the 2080s with the UK and central Europe among the most severely affected.2 More than 1000 people were killed by floods and 5·6 million more affected in Europe in the past 10 years alone.3 As climate change progresses, flooding events are expected to increase in frequency and intensity due to rising sea levels and more frequent and extreme precipitation events,2 and increased urbanisation will expose more people to flooding events.
Synergistic effect of combined PI3K and PLK1 inhibition in anaplastic thyroid carcinoma cells.
Authors: Emrullah Yilmaz, Devora Champa, Antonio Di Cristofano
Journal: Journal of Clinical Oncology (2015)

e22205 Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer. Despite recent efforts aimed at defining its most common molecular alterations, there is still no effective treatment. PI3K, RAS and BRAF are some of the key driver oncogenic pathways defined by molecular studies. Furthermore, overexpression of PLK1 is extremely common. We evaluated the effect of combining inhibitors of PLK1 and PI3K in PI3K active ATC cell lines. Methods: Cell lines with p53 deletion and PI3K activation were used. Cell viability was evaluated by WST-1 assay after 72 hours treatment. Treatment responses were evaluated using GraphPad software and synergy was evaluated by determining the combination index using ComboSyn software. Results: Treatment with the PLK1 inhibitor BI2536 resulted in significant apoptosis and cell cycle arrest in all ATC cell lines, independent of their driver mutation. However, PI3Khighcells displayed mitotic slippage, suggesting a possible mechanism leading to resistance. Combination of BI2536 with the PI3K inhibitor BKM120 resulted in significant synergy, especially when BKM120 was added 24 hours after pretreatment with BI2536. Then we tested the effect of a more potent PLK1 inhibitor, BI6727. Combination of BI6727 and BKM120 resulted in significant synergy after 72 hours treatment. Simultaneous treatment was more effective than sequential treatment. Finally, we treated cells with Rigosertib, which is a multi-kinase inhibitor with reported effect on PI3K and PLK1. Interestingly, ATC cells were quite resistant to a wide range of Rigosertib concentrations, suggesting that this inhibitor is targeting different molecules. Conclusions: Inhibition of the driver oncogenic pathway PI3 kinase sensitizes ATC to PLK1 inhibitors in PI3K active tumors. This suggests the role of using combination therapies in this aggressive tumor.
Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action
Authors: Yin Kwan Wong, Chengchao Xu, Karunakaran A. Kalesh, Yingke He, Qingsong Lin, W. S. Fred Wong, Han‐Ming Shen, Jigang Wang
Journal: Medicinal Research Reviews (2017)

Abstract Artemisinin and its derivatives (collectively termed as artemisinins) are among the most important and effective antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their antimalarial effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both in vitro and in vivo. These effects appear to be mediated by artemisinin‐induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of cancer. Great strides have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of artemisinin. Moreover, encouraging data have also been obtained from a limited number of clinical trials to support their anticancer property. However, there are several key gaps in knowledge that continue to serve as significant barriers to the repurposing of artemisinins as effective anticancer agents. This review focuses on important and emerging aspects of this field, highlighting breakthroughs in unresolved questions as well as novel techniques and approaches that have been taken in recent studies. We discuss the mechanism of artemisinin activation in cancer, novel and significant findings with regards to artemisinin target proteins and pathways, new understandings in artemisinin‐induced cell death mechanisms, as well as the practical issues of repurposing artemisinin. We believe these will be important topics in realizing the potential of artemisinin and its derivatives as safe and potent anticancer agents.
Genetic, clinical and pathological characteristics of BRCA-associated breast cancer (BC) in Hispanic patients in the United States (US) and Latin America (LatAm).
Authors: Yanin Chavarri Guerra, Sharon Sand, Marcia Cruz Correa, Pamela Ganschow, Nancy Cohen, Frederic C. Kass, Ian K. Komenaka, Carolyn B. Hendricks, Christopher Hake, Jane Kanowitz, Annette Campbell Fontaine, Gary Walter Unzeitig, Nancy Renee Feldman, Deborah Kerlin, Adrian Daneri-Navarro, Danielle Castillo, Josef Herzog, Nancy Guerrero-Llamas, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2017)

1539 Background: Hispanic women with BC present at a younger age, have a higher frequency of BRCA mutations and show a worse incidence-to-mortality ratio than non-Hispanic women. Information regarding the characteristics of BRCA-associated BC in Hispanics is limited. Here, we assess differences in BRCA-associated BC between Hispanic patients in the US and in LatAm. Methods: Hispanic patients from the US and LatAm (Mexico, Colombia, Peru, and Puerto Rico) with a history of BRCA-associated BC enrolled in the Clinical Cancer Genomics Community Research Network registry were included. We compared the genetic, demographic, clinical and pathologic characteristics between Hispanics from the US and LatAm using Fisher’s exact test and x 2 statistics. Results: Between 1997 and 2016, 3670 Hispanic patients with a history of BC from LatAm (n = 1341) and the US (n = 2329) were identified, of which 490 (13.3%) had a deleterious BRCA mutation. The frequency of BRCA mutations was similar in Hispanics from LatAm (13.8%, n = 185) and the US (13.1%, n = 305). No significant differences were found in the frequency of BRCA1 vs BRCA2 mutations between patients from LatAm (BRCA1 68%, BRCA2 31.8%) and the US (BRCA1 61.3%, BRCA2 39%) (p = .12). The most frequent mutations found in BRCA1 were: ex 9-12del (LatAm n = 24, US n = 15), 185delAG (LatAm n = 13, US n = 18) and 943ins10 (LatAm n = 3, US n = 8), and in BRCA2 3492insT (LatAm n = 3, US n = 28). Mean age at BC diagnosis was 39.1 (SD 9.5) in LatAm and 41.7 (SD 10.6) in the US (p = 0.01). US patients were significantly more likely to present with Stage 0-II BC than those from LatAm (77.1% vs. 47.6%, p &lt; .001). We found no differences in the proportion of hormone receptor positive tumors between patients from LatAm (45%) and the US (47%) (p = .78). Conclusions: The frequency of BRCA-associated BC was similar between Hispanics in LatAm and the US. Women from LatAm with BRCA mutations present at a younger age, as seen for sporadic BC; the causes for this finding warrant further research. Women with BRCA-associated BC in LatAm are more likely to have advanced BC at presentation, which may be a reflection of disparities and barriers in access to care.
High-Quality Statin Trials Support the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines After the HOPE-3 Trial (Heart Outcomes Prevention Evaluation-3): MESA (The Multiethnic Study of Atherosclerosis)
Authors: Martin Bødtker Mortensen, Matthew Budoff, Dong Li, Khurram Nasir, Michael J. Blaha, Veit Sandfort, Carlos Jose Rodriguez, Pamela Ouyang, Erling Falk
Journal: Circulation (2017)
A randomized trial of selenium and vitamin E for primary prevention of non-melanoma skin cancer: Trial results and experience from a low-resource setting.
Authors: Maria Argos, James J. Dignam, Faruque Parvez, Mahfuzar Rahman, Samar K Hore, Mohammad H Shahriar, Golam Sarwar, Tariqul Islam, Vesna Slavkovich, Joseph Graziano, Mary Gamble, Judith Harjes, Kristen Anton, Muhammad Ghulam Kibriya, Farzana Jasmine, Mohammed Kamal, Christopher R Shea, Md Yunus, John A. Baron, Habibul Ahsan
Journal: Journal of Clinical Oncology (2017)

1511 Background: Selenium and vitamin E supplementation previously have shown some evidence of a beneficial effect in the secondary prevention of non-melanoma skin cancer (NMSC). More than 100 million people worldwide are at increased risk of NMSC and other cancers due to arsenic exposure from drinking water and diet – a risk that persists for several decades even after the exposure has terminated. Here, we report on the design, methods and main results of the Bangladesh Vitamin E and Selenium Trial (BEST) – a population-based chemoprevention study conducted among 7,000 adults with visible arsenic toxicity. Methods: BEST is a 2 × 2 full factorial, double-blind, randomized placebo controlled trial of 7,000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of NMSC incidence. Results: Excellent compliance was maintained through the course of the trial, based on data from pill counts, self-reported compliance, and bioadherence. Among participants on treatment through the end of the 6-year intervention period, &gt; 85% were adherent to at least 80% of study supplements. More than 500 new NMSC cases were ascertained using a three-tiered biopsy protocol. No significant beneficial effects were observed on NMSC incidence during the study period for selenium or vitamin E. Among more than 500 observed deaths (including 182 cancer-related deaths), there were also no significant treatment effects on total mortality, cancer-related mortality or arsenical cancer-related mortality. Conclusions: This large population-based trial does not support any beneficial effect of vitamin E or selenium supplementation for the primary prevention of NMSC or mortality in an arsenic-exposed population. With the rapidly increasing burden of preventable cancers in low- and middle-income countries, efficient and feasible chemoprevention study designs and approaches, such as employed in Bangladesh, may prove impactful in conceiving large scale cancer chemoprevention trials in low-resource settings. Clinical trial information: NCT00392561.
A qualitative perspective on oncologist attitudes, barriers and strategies to practicing patient- and family-centered care.
Authors: Timothy K. Nguyen, Glenn Bauman, Christoper J Watling, Karin Hahn
Journal: Journal of Clinical Oncology (2016)

e18014 Background: There is a growing recognition that patient- and family-centered care (PFCC) is a vital part of healthcare reform with rich opportunities for improvement within oncology. A shift towards PFCC requires participation across all stakeholders and despite the importance of physician buy-in, research examining their perspectives on PFCC is lacking. We sought to explore oncologists’ perspectives on PFCC, including their engagement with its core principles and to identify factors that influence their ability to practice PFCC. Methods: We conducted semi-structured interviews with 18 oncologists (8 radiation, 4 medical, 4 surgical, 2 hematologist-oncologists) at a single Canadian academic cancer institution. Interview data were analyzed using thematic analysis and principles drawn from grounded theory. Subsequently, focus groups consisting of the interviewed participants were facilitated to confirm and elaborate on the identified themes. Constant comparisons were used to identify recurring themes. Results: Two dominant themes emerged. First, physicians displayed cautious engagement in their approach to PFCC. Collectively, participants understood the general principles of PFCC and agreed that patient autonomy was a critical component. However, there was a limited understanding of the value, implications and motivation for improving PFCC which may lead to reluctance with physician buy-in. Second, both individual and system barriers to practicing PFCC were identified. A lack of physician acknowledgement and engagement, and competing responsibilities emerged as provider-level challenges. Overall, system barriers were related to limited institutional resources and included impaired clinic workflow, infrastructure constraints and delayed access to care. Physician-specific PFCC best practices were also elicited pertaining to patient communication and streamlining care. Conclusions: Advancing PFCC at our institution will require continued education of physicians regarding PFCC, acknowledgement and preservation of the PFCC behaviors already in practice and creative solutions to address the system barriers to enacting PFCC.
Precision prostate cancer chemoprevention with gamma-tocotrienol.
Authors: Christine Ann Moore, Victoria Palau, Janet Lightner, Marianne Brannon, William Stone, Koyamangalath Krishnan
Journal: Journal of Clinical Oncology (2017)

e13043 Background: A goal of precision chemoprevention is to prevent or delay cancer progression by using minimally toxic agents guided by knowledge of alterations in oncogenic molecular pathways and signaling cascades. Indolent prostate cancer can benefit from chemopreventive agents by delaying growth. Vitamin E is not a single compound and refers to four tocopherols and four tocotrienols. The use of all-racemic-alpha tocopheryl acetate in preventing cancer was studied in the SELECT clinical trial. This trial found it was not chemopreventive and could promote prostate cancer. We compared the abilities of RRR-alpha-tocopherol (AT), RRR-gamma-tocopherol (GT), and gamma-tocotrienol (GT3) in preventing growth of two prostate cancer cell lines (LNCaP and PC-3) and a control prostate cell line (RWPE-1) by quantifying their effects on two signaling pathways known to be pivotal in prostate carcinogenesis, AKT and MAP Kinase (pERK). Methods: LNCaP, PC-3, and RWPE-1 cell lines were treated with increasing concentrations of AT, GT and GT3 in DMEM, and cytotoxicity determined by MTS cell culture experiments. We determined the effect of GT3 on signaling pathways by analyzing B-actin, P-AKT and p-ERK in combination with AKT and/or MEK inhibitors via Western immunoblot and PCR analysis. Results: Initial experiments with LNCaP and PC-3 cells showed GT3 induced the expression of pERK and p-c-JUN, inhibited cell growth and promoted apoptotic cell death. Neither AT nor GT had these effects. AKT was not activated by AT, GT or GT3. Inhibition of AKT activation via MK-2206 did not block GT3 growth inhibition in LNCaP cells. No growth inhibition was found with RWPE-1 control cells in presence of AT, GT or GT3 yet GT3 induced pERK expression. AT did not interfere with cancer growth inhibition and did not block the anticancer effects of GT3. Conclusions: GT3 induces the activation of pERK but this effect is not sufficient to account for the in vitro chemopreventive effects of this form of vitamin E. The AKT pathway is not modulated by GT3 and does not appear to be relevant to GT3 killing of PC-3 or LNCaP. Of five signaling pathways implicated in prostate carcinogenesis, we explored AKT and pERK. Future research will explore B-catenin, mTOR and PI3K.
Persistent distress increases mortality in patients with coronary artery disease, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Persistent, moderate to severe psychological distress is associated with significantly increased mortality in patients with stable coronary artery disease, a large follow-up study has shown.1

Previous research has found an increased risk of cardiovascular events in people with symptoms of depression and anxiety. But studies in patients with coronary heart disease have assessed psychological wellbeing only once in the study, …
Changes in Sedimentation of Surfactant in Ventilated Excised Rat Lungs
Authors: Lyn Aung Thet, Linda Clerch, Gloria D. Massaro, Donald Massaro
Journal: Journal of Clinical Investigation (1979)

We ventilated excised rat lungs at a constant tidal volume (CTV); they developed areas of atelectasis which could be reversed by a large inflation (CTV + I) or prevented by the addition of positive end-expiratory pressure to the CTV. To explore the possibility that these modes of ventilation led to changes in surfactant, we lavaged the lungs and centrifuged the returns at 500 g; we measured the amount of disaturated phosphatidylcholine (DSPC) in the resultant pellet and supernatant fluid as a marker for surfactant. We found 16.9±1.5 (mean±SE), 38.0±2.4, 18.3±1.6, and 21.7±2.3% of the total lavage DSPC, in the pellet from freshly excised, CTV, CTV + I, and positive end-expiratory pressure to the CTV lungs, respectively. The total amount of lavage DSPC was the same in all groups.