tbuckley/cabot-search huggingface dataset:
GRB7 and HER2 protein overexpression and breast cancer outcome
Authors: S. Luoh, E. E. Ramsey, T. Bai, E. J. Keenan
Journal: Journal of Clinical Oncology (2009)

11102 Background: The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule and is located in close proximity to human epidermal growth factor receptor 2 (HER2) on chromosome 17q11–12. This study examines the roles of GRB7 protein in human breast cancer. Methods: We performed western blotting analysis of protein extracts from 563 annotated frozen breast tumors, collected from 1988 - 1998. GRB7 and HER2 bands were assigned low or high values compared to specific protein controls, and tubulin bands. Chi-square tests were used to test the hypothesis that there was no association between expression status of GRB7 or HER2 with clinical covariates and outcomes. Univariate Cox regression was performed to identify risk factors and Cox proportional hazards backward step model for variable selection to identify independent predictors of progression free survival. All P values were two sided. P values less than 0.05 were considered statistically significant. HER 2 gene amplification status was determined by fluorescence in situ hybridization (FISH). Results: GRB7 protein over-expression was associated with negative estrogen (&lt; 5 fmole/mg protein) and progesterone receptor (&lt; 10fmole/mg protein) status, higher grade (1, 2, or 3), larger primary tumor size (&lt; 2.0 vs. &gt; 2.0 cm), (more) axillary lymph node involvement (continuous), higher clinical stage (1, 2, 3, or 4) and shortened progression free survival (months). We found a discrepancy in HER2 and GRB7 protein over-expression. Isolated GRB7 protein over-expression correlated with inferior progression free survival, while HER2 protein over-expression without GRB7 protein over-expression did not. Multivariate analysis revealed that GRB7 over-expression was an independent predictor of progression free survival (hazard ratio 1.69: 95% confidence interval, 1.073 - 2.672; P = 0.0236). All 18 tumors submitted to FISH analysis that over-expressed both HER2 and GRB7 proteins and no tumors (0 / 10) with HER2 but no GRB7 protein over-expression demonstrated HER2 gene amplification. Conclusions: GRB7 protein over-expression is an independent adverse prognostic factor in breast cancer. No significant financial relationships to disclose.
Phase II Study of Pemetrexed + Erlotinib in Pretreated Non-Sq-Nsclc Pts with Wtegfr(Talimta Study)
Authors: Takashi Nishimura, Young Hak Kim, Hiroki Nagai, Hiroaki Ozasa, Yuichi Sakamori, Shigeaki Iwatsubo, Tomoko Nishimura, Hironobu Sunadome, Toshiyuki Iwata, Michiaki Mishima
Journal: Annals of Oncology (2014)
Early Results Of a Phase II Study Of Lenalidomide and Rituximab As Frontline Treatment Of Patients With Chronic Lymphocytic Leukemia
Authors: Paolo Strati, Michael J. Keating, Christina Hinojosa, Stefan Faderl, Susan C. Smith, Susan O'Brien, Jan A. Burger, William G. Wierda, Alessandra Ferrajoli
Journal: Blood (2013)
Proteolytic Enzymes in Tumor Metastasis. I. Plasminogen Activator in Clones of Lewis Lung Carcinoma and T10 Sarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L Eisenbach, S Segal, M Feldman
Journal: JNCI Journal of the National Cancer Institute (1985)

Plasminogen activator (PA; urokinase) levels were studied in metastatic and nonmetastatic clones of the Lewis lung carcinoma (3LL) and of the T10 sarcoma. Tests of clones grown in vitro revealed that the cell content and secretion of PA correlated positively with the metastatic capacity of the clones of both tumors. When cell-associated activities were examined in cloned cell populations grown subcutaneously in vivo, the apparent activities in the solid tumors produced by low-metastatic clones were equal to or even higher than those in solid tumors produced by high-metastatic clones. This finding was attributed to the observation that solid tumors produced by low-metastatic clones, but not those produced by high-metastatic clones, were highly infiltrated with macrophages. Subsequent tests indicated that the ip inoculation of X-irradiated or mitomycin-treated tumor cells of low-metastatic clones elicited a significantly greater peritoneal infiltration of macrophages than did tumor cells of high-metastatic clones. Such “tumor-associated” macrophages manifested high levels of PA, whereas resident (nonactivated) peritoneal macrophages did not. These findings suggest that although PA may cause the initial detachment from the local tumor of both nonmetastatic (via the macrophage PA) and metastatic cells (via their own PA), the PA secreted by the metastatic cells may enable them to complete subsequent stages of the metastatic process that may be PA-dependent.
A Discrete Choice Experiment to Examine the Preferences of Patients With Cancer and Their Willingness to Pay for Different Types of Health Care Appointments
Authors: Shu Fen Wong, Richard Norman, Trisha Lynette Dunning, David Michael Ashley, Mustafa Khasraw, Theresa Margaret Hayes, Ian Collins, Paula Kate Lorgelly
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: This study sought to understand the preferences of patients with cancer and the trade-offs between appointment attributes using discrete choice experiment (DCE). Methods and Study Design: Patients with cancer at 3 hospitals completed a self-administered DCE. Each scenario described 6 attributes: expertise of health care professionals (HCPs), familiarity of doctors with patients' medical history, waiting time, accompaniment by family/friends, travel time, and out-of-pocket costs. Patient preferences were estimated using logistic regression. Willingness to pay (WTP) estimates were derived from regression coefficients. Results: Of 512 patients contacted, 185 returned the questionnaire. The mean age was 61 years, and 60% of respondents were female. The mean time since cancer diagnosis was 34 months, 90% had received treatment; and 61% had early-stage disease. The most important attributes were expertise and familiarity of doctors with patients' medical history; distance traveled was least likely to influence patient preferences. The WTP analysis estimated that patients were willing to pay $680 (95% CI, 470–891) for an appointment with a specialist, $571 (95% CI, 388–754) for doctors familiar with their history, $422 (95% CI, 262–582) for shorter waiting times, $399 (95% CI, 249–549) to be accompanied by family/friends, and $301 (95% CI, 162–441) for shorter traveling times. Male patients had a stronger preference for accompaniment by family/friends. The expertise of HCP was the most important attribute for patients regardless of geographic remoteness. Conclusions: Our study can assist the development of patient-centered health care models that improve patient access to experienced HCPs, support the role of primary care providers during the cancer journey, and educate patients about the roles of non-oncology HCPs to cope with increasing demand for cancer care.
The predictive value of HGPIN and ASAP for the subsequent diagnosis of prostate cancer in the Reduction by Dutasteride of Cancer Events (REDUCE) study.
Authors: D. G. Bostwick, D. J. Tindall, C. A. Pettaway, T. L. Tammela, C. Teloken, T. H. Wilson, R. S. Castro
Journal: Journal of Clinical Oncology (2010)

4561 Background: REDUCE was a 4-year, randomized placebo (pbo) controlled study of prostate cancer (PCa) risk reduction with once daily dutasteride 0.5 mg (dut). This analysis examines the effect of dut on initial detection of high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP) and the incidence of PCa on subsequent biopsy. Methods: Eligible men were aged 50–75 years, had a serum PSA 2.5–10.0 ng/ml, and a single, negative (no PCa, HGPIN or ASAP) biopsy of 6–12 cores in the 6 months prior to enrollment (4126 subjects randomized to pbo, 4105 dut). Ten-core prostate biopsies were taken at 2 and 4 years and examined for evidence of PCa. For subjects with 2-year biopsies and no PCa (2866 pbo, 2867 dut), the initial incidence of ASAP, HGPIN (without ASAP), and ASAP or HGPIN was compared between treatment groups using Fisher's exact test. PCa incidence in a subsequent biopsy was also compared between treatment groups with Fisher's exact test. Results: PCa incidence in subjects biopsied was 17.2% (pbo) and 13.4% (dut) in Years 1–2; and 11.8% (pbo) and 9.1% (dut) in Years 3–4. Dut was associated with a lower incidence of ASAP and/or HGPIN (p≤0.007; Table). For subjects with ASAP and/or HGPIN in initial study biopsy who had a subsequent biopsy (median time between biopsies 2 years), the incidence of PCa was higher vs. overall PCa incidence during Years 3–4. If a man was diagnosed with HGPIN or ASAP while taking dut, the likelihood of a future PCa diagnosis was similar to that of the pbo group. Conclusions: HGPIN and ASAP conferred a 2- and 3-fold increased risk of subsequent PCa, respectively compared to the overall rates for PCa in Years 3–4. Dut significantly reduced the incidence of HGPIN and/or ASAP with no significant differences vs. pbo observed in the risk of subsequent PCa. Incidence Pbo Dut p value ASAP 1st dx ASAP 206/2,866 (7.2%) 156/2,867 (5.4%) 0.007 Subsequent PCa 39/116 (33.6%) 29/95 (30.5%) 0.66 HGPIN and no ASAP 1st dx HGPIN 243/2,866 (8.5%) 143/2,867 (5.0%) <0.0001 Subsequent PCa 23/109 (21.1%) 12/63 (19.0%) 0.85 ASAP and/or HGPIN 1st dx ASAP/HGPIN 434/2,866 (15.1%) 288/2,867 (10.0%) <0.0001 Subsequent PCa 61/221 (27.6%) 40/153 (26.1%) 0.81 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bostwick Laboratories, Ferring Pharmaceutical, GlaxoSmithKline Astellas Pharma, GlaxoSmithKline, Orion Pharma Bostwick Laboratories, GlaxoSmithKline Astellas Pharma, Ferring Pharmaceutical, GlaxoSmithKline, Orion Pharma GlaxoSmithKline GlaxoSmithKline
Enfortumab Vedotin Antibody–Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models
Authors: Pia M. Challita-Eid, Daulet Satpayev, Peng Yang, Zili An, Karen Morrison, Yuriy Shostak, Arthur Raitano, Rossana Nadell, Wendy Liu, Dawn Ratay Lortie, Linnette Capo, Alla Verlinsky, Monica Leavitt, Faisal Malik, Hector Aviña, Claudia I. Guevara, Nick Dinh, Sher Karki, Banmeet S. Anand, Daniel S. Pereira, Ingrid B.J. Joseph, Fernando Doñate, Kendall Morrison, David R. Stover
Journal: Cancer Research (2016)

Abstract The identification of optimal target antigens on tumor cells is central to the advancement of new antibody-based cancer therapies. We performed suppression subtractive hybridization and identified nectin-4 (PVRL4), a type I transmembrane protein and member of a family of related immunoglobulin-like adhesion molecules, as a potential target in epithelial cancers. We conducted immunohistochemical analysis of 2,394 patient specimens from bladder, breast, lung, pancreatic, ovarian, head/neck, and esophageal tumors and found that 69% of all specimens stained positive for nectin-4. Moderate to strong staining was especially observed in 60% of bladder and 53% of breast tumor specimens, whereas the expression of nectin-4 in normal tissue was more limited. We generated a novel antibody–drug conjugate (ADC) enfortumab vedotin comprising the human anti-nectin-4 antibody conjugated to the highly potent microtubule-disrupting agent MMAE. Hybridoma (AGS-22M6E) and CHO (ASG-22CE) versions of enfortumab vedotin (also known as ASG-22ME) ADC were able to bind to cell surface–expressed nectin-4 with high affinity and induced cell death in vitro in a dose-dependent manner. Treatment of mouse xenograft models of human breast, bladder, pancreatic, and lung cancers with enfortumab vedotin significantly inhibited the growth of all four tumor types and resulted in tumor regression of breast and bladder xenografts. Overall, these findings validate nectin-4 as an attractive therapeutic target in multiple solid tumors and support further clinical development, investigation, and application of nectin-4–targeting ADCs. Cancer Res; 76(10); 3003–13. ©2016 AACR.
The real cost of sequencing: scaling computation to keep pace with data generation
Authors: Paul Muir, Shantao Li, Shaoke Lou, Daifeng Wang, Daniel J Spakowicz, Leonidas Salichos, Jing Zhang, George M. Weinstock, Farren Isaacs, Joel Rozowsky, Mark Gerstein
Journal: Genome biology (2016)

As the cost of sequencing continues to decrease and the amount of sequence data generated grows, new paradigms for data storage and analysis are increasingly important. The relative scaling behavior of these evolving technologies will impact genomics research moving forward.
Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma
Authors: Jatin J. Shah, Edward A. Stadtmauer, Rafat Abonour, Adam D. Cohen, William I. Bensinger, Cristina Gasparetto, Jonathan L. Kaufman, Suzanne Lentzsch, Dan T. Vogl, Christina L. Gomes, Natalia Pascucci, David D. Smith, Robert Z. Orlowski, Brian G. M. Durie
Journal: Blood (2015)
Strategies for the Treatment of Acute Promyelocytic Leukemia
Authors: Olga Frankfurt, Martin S. Tallman
Journal: Journal of the National Comprehensive Cancer Network (2006)

The outcome of acute promyelocytic leukemia (APL) has improved dramatically during the past 40 years. Insights into the genetic and biologic mechanisms of APL lead to the development of specific and effective therapeutic strategies. This article discusses the therapeutic interventions that transformed APL from one of the most lethal leukemias to one that is highly curable.
A Discordant Cutaneous Eruption in a Neonatal Twin
Authors: William E. Damsky, Brittany G. Craiglow, Jaehyuk Choi
Journal: JAMA Dermatology (2016)

A male neonate born prematurely at 27 weeks’ gestational age had a erythematous eruption at birth, exhibiting 100 to 200 pink papules, 0.05 to 0.2 cm in size, distributed on the trunk, extensor upper arms, and upper legs. What is your diagnosis?
Alterations in Membrane Structure and Function Associated With Neoplastic Transformation In Vitro 1
Authors: M. K. Patterson
Journal: JNCI Journal of the National Cancer Institute (1974)

Selected alterations in membrane structure associated with in vitro transformation appear amenable to rapid assay procedures. Most reported alterations, however, lack the specificity required for meaningful testing. These membrane changes are discussed in regard to specificity of transforming systems, cell types, and origin.
Purpuric and petechial rashes in adults and children: initial assessment
Authors: Angela E Thomas, Susan F Baird, Julia Anderson
Journal: BMJ (2016)

#### What you need to know

Bleeding into the skin or mucosa from small vessels produces a purpuric rash, or smaller petechiae (1-2 mm in diameter). Purpura is not a diagnosis but can be the presenting feature of serious conditions, such as meningococcal sepsis and acute leukaemia, which require urgent diagnosis and management. Equally, it can cause patients alarm but requires little more than a single assessment and reassurance. Differentiating between the two scenarios is important. This article focuses on recognition of the serious diagnoses and recommendations for urgent referral. Once such diagnoses have been excluded, other causes can be investigated or the patient managed by observation alone.

A cardinal sign of a purpuric rash is that it does not blanch on pressure, unlike exanthema, telangiectases, or allergic rashes. This sign of meningococcal sepsis has been the subject of public health campaigns to help parents recognise its importance and seek urgent medical attention (fig 1⇓).



Fig 1  Petechial rash in invasive meningococcal disease



It is crucial to assess for features of serious illness in all patients with purpura.

Patients with purpura can generally …
Carfilzomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma: Final Results from the NCI Phase 2 Pilot Study
Authors: Ola Landgren, Mark Roschewski, Sham Mailankody, Mary Kwok, Elisabet E. Manasanch, Manisha Bhutani, Nishant Tageja, Dickran Kazandjian, Adriana Zingone, Rene Costello, Debra Burton, Yong Zhang, Peter Wu, George Carter, Marcia Mulquin, Diamond Zuchlinski, Ashley Carpenter, Verena Gounden, Candice Morrison, Irina Maric, Katherine R. Calvo, Raul C. Braylan, Constance Yuan, Maryalice Stetler-Stevenson, Diane C Arthur, Liza Lindenberg, Kurdziel Karen, Peter Choyke, Seth M. Steinberg, William D Figg, Neha Korde
Journal: Blood (2014)
Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review
Authors: Wasiu A Olowu, Abdou Niang, Charlotte Osafo, Gloria Ashuntantang, Fatiu A Arogundade, John Porter, Saraladevi Naicker, Valerie A Luyckx
Journal: The Lancet Global Health (2016)

BackgroundAccess to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care.MethodsWe searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best reflect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690.FindingsWe identified 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex.InterpretationPatients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa.FundingNone.
Lifesum: easy and effective dietary and activity monitoring
Authors: Matthew S Tredrea, Vincent J Dalbo, Aaron T Scanlan
Journal: British Journal of Sports Medicine (2016)

Lifesum.

Fitness or health.

Apple (iOS 7.0 or later); Android (V.4.03 and up).

Trial—Free. 

Lifesum allows users to monitor food intake and daily activity (figure 1). The user utilises a search bar to display an activity or food item database from which the most suitable option can be selected and adjusted for time of activity completed or amount of food consumed.



Figure 1 

The free version of the application determines daily intake targets based on input from the user regarding age, body mass and general goals. The upgraded version uses additional variables to estimate daily energy requirements. Daily targets are divided by nutrient, with targets set for total kilojoules, carbohydrate, protein and fat (figure 2). In the upgraded version, daily targets are further divided to provide information with respect to micronutrient intake. As the user inputs information in …
NFAT1 Directly Regulates IL8 and MMP3 to Promote Melanoma Tumor Growth and Metastasis
Authors: Einav Shoshan, Russell R. Braeuer, Takafumi Kamiya, Aaron K. Mobley, Li Huang, Mayra E. Vasquez, Guermarie Velazquez-Torres, Nitin Chakravarti, Cristina Ivan, Victor Prieto, Gabriel J. Villares, Menashe Bar-Eli
Journal: Cancer Research (2016)

Nuclear factor of activated T cell (NFAT1, NFATC2) is a transcription factor that binds and positively regulates IL2 expression during T-cell activation. NFAT1 has important roles in both innate and adaptive immune responses, but its involvement in cancer is not completely understood. We previously demonstrated that NFAT1 contributes to melanoma growth and metastasis by regulating the autotaxin gene (Enpp2). Here, we report a strong correlation between NFAT1 expression and metastatic potential in melanoma cell lines and tumor specimens. To elucidate the mechanisms underlying NFAT1 overexpression during melanoma progression, we conducted a microarray on a highly metastatic melanoma cell line in which NFAT1 expression was stably silenced. We identified and validated two downstream targets of NFAT1, IL8, and MMP3. Accordingly, NFAT1 depletion in metastatic melanoma cell lines was associated with reduced IL8 and MMP3 expression, whereas NFAT1 overexpression in a weakly metastatic cell line induced expression of these targets. Restoration of NFAT1 expression recovered IL8 and MMP3 expression levels back to baseline, indicating that both are direct targets of NFAT1. Moreover, in vivo studies demonstrated that NFAT1 and MMP3 promoted melanoma tumor growth and lung metastasis. Collectively, our findings assign a new role for NFAT1 in melanoma progression, underscoring the multifaceted functions that immunomodulatory factors may acquire in an unpredictable tumor microenvironment. Cancer Res; 76(11); 3145-55. ©2016 AACR.
Pilot study of intra-arterial bevacizumab for hepatocellular carcinoma HCC
Authors: K. El-Shami
Journal: Journal of Clinical Oncology (2008)

15681 Background: HCC is a major cause of cancer death worldwide with limited and minimally efficacious therapeutic options foro advanced HCC. Bevacizumab is a monoclonal antibody against VEGFA pilot study of Bevacizumab was conducted to evaluate the antitumor activities and the toxicity of intra-hepatic artery administration in previously untreated patients with advanced HCC. Methods: Patients with locally advanced HCC were treated with transcatheter arterial injection of bevacizumab at a dose of 5 mg/kg given via superselective catheter.The responses were evaluated by computed tomography 2 months after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors, and lipiodol accumulation in tumors was regarded as indicating necrosis. Results: Between 3/07 and 12/07, ten patients were treated. Patients had Child Pugh A or B. Barcelona staging C. The average number of doses administed was 2.2/10 patient achieved CR lasting for 4 months. An additional 6 patients showed partial response, and the remaining two patients showed stable disease (duration 6 months). Seven patients achieved a serologic response (defined by >50% drop in AFP levels) following 2 doses of bevacizumab. There was no toxicity associated with intraarterial administration of bevacizumab more than grade 2. Conslusion: Bevacizumab administered into the hepatic artery is a well tolerated and efficacious treatment in advanced HCC. Further studies to evaluate this modality in larger studies are warranted. No significant financial relationships to disclose.
Nothing About Us Without Us: Developing Innovative Technologies for, by and with Disabled Persons
Authors: Christopher Newell
Journal: BMJ (2000)

David Werner 

Health Wrights, pp 360 ISBN 0 9655585 3 3

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A recurrent theme from disabled people over the past 20 years is “nothing about us without us.” This aptly titled book gives many practical reasons for including disabled people in technological and rehabilitation programmes. Written by the author of Disabled Village Children and Where There Is No Doctor , this book is a clear development of his previous work. The focus of this book is on developing appropriate and innovative technologies in developing countries. Yet …

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