tbuckley/cabot-search huggingface dataset:
Replication Stress: An Achilles' Heel of Glioma Cancer Stem–like Cells
Authors: Meredith A. Morgan, Christine E. Canman
Journal: Cancer Research (2018)

Glioblastoma (GBM) is a highly aggressive form of cancer that is resistant to standard therapy with concurrent radiation and temozolomide, two agents that work by inducing DNA damage. An underlying cause of this resistance may be a subpopulation of cancer stem-like cells that display a heightened DNA damage response (DDR). Although this DDR represents an attractive therapeutic target for overcoming the resistance of GBMs to radiotherapy, until now, the cause of this DDR upregulation has not been understood. In a previous issue of Cancer Research, Carruthers and colleagues investigated DNA replication stress as an underlying mechanism responsible for upregulation of the DDR and hence the radiation resistance of glioma stem-like cells. Furthermore, the authors explore the efficacy of combined ataxia telangiectasia and Rad3-related kinase and PARP inhibitors as a strategy to leverage these mechanisms and overcome radiation resistance.See related article by Carruthers and colleagues, Cancer Res; 78(17); 5060-71.
Addressing health disparities in survivors of breast cancer through lifestyle modifications and group support.
Authors: Susan H. McDunn, Olatokunbo Olorunfemi, Wendy Rogowski, Bettina Tahsin, Venita James, Karen Giese, Harry Miranda- Ocasio, Leon Fogelfeld
Journal: Journal of Clinical Oncology (2018)

177 Background: Obesity and inactivity have been shown to adversely affect outcomes in survivors of breast cancer. These factors may contribute to poorer outcomes in women of black and Hispanic populations, and those from lower socioeconomic backgrounds. We sought to improve overall well-being and limit weight gain in patients from these underserved populations through a group lifestyle intervention in a public hospital setting. Methods: 46 women were recruited and gave informed consent after completion of adjuvant chemotherapy for stage I-III breast cancer to participate in this feasibility pilot program. Blood work, body measurements, diet, two-minute walk tests, and PHQ9 depression scores were collected at the first and last of six monthly sessions. The group classes were led by a registered dietician and included diet and light exercise instruction at each visit. Results: Patient demographics and results are in the table below. Trends for non-completers included younger age, ethnicity, no hormonal therapy, lower baseline weight, lower HOMA IR, and dropout after two sessions. Among the 40% who completed all six sessions, there was a trend toward greater well-being (lower PHQ) with slight weight gain and increased insulin resistance. Completers tended to start in the same cohort and were more likely to complete if they attended more than two visits. Conclusions: Greater well-being may be an important outcome for group lifestyle improvement programs in populations with disparities. Motivations for better attendance may include group bonding. Participants will continue to be followed to obtain information on long-term weight change and cancer recurrence.[Table: see text]
Social isolation: Impact on treatment and survival in patients with advanced cancer.
Authors: Sara Moore, Bonnie Leung, Alan Bates, Cheryl Ho
Journal: Journal of Clinical Oncology (2018)

156 Background: Social relationships are an important determinant of health, with impacts on morbidity and mortality in the general population. The influence of social isolation in patients with metastatic cancer is less clear, as are the potential mechanisms of its effect. We sought to examine patient-reported social support in a large unselected population, and explore the impact on outcome. Methods: A retrospective review was completed of all patients with metastatic cancer referred to BC Cancer from 2011-2016 who completed a psychological screen within six months of diagnosis. Social isolation was defined as a positive response to any of five questions about social support: live alone, recently lost spouse/partner, no regular contact with friends/relatives, no one to assist with IADLs, no emotional support. An isolation score was calculated as the number of positive responses. The primary outcome was overall survival (OS). Results: 7,699 patients were included in the study. Baseline characteristics: median age 68, 57% male, 60% received systemic therapy, primary tumor site 4% breast / 37% lung / 28% GI / 13% GU / 18% other. 5191 (67%) patients reported no isolation, and 2,538 (33%) were socially isolated. Patients with social isolation were more likely older (median age 70 vs. 67), female (50% vs. 40%), ECOG ≥2 (34% vs. 30%), and receive no systemic therapy (46% vs. 35%). Median OS was inferior in socially isolated patients at 10.1 m compared to those with no isolation at 13.5 m (p&lt;0.001). In a multivariate model including age, sex, ECOG, systemic therapy, and primary tumor site, the impact of social isolation on OS remained significant (HR 1.06, p=0.04). In an exploratory analysis, increasing levels of social isolation were correlated with reduced systemic therapy uptake (score 0=65% received systemic therapy, 1=56%, 2=53%, 3=47%, ≥4=43%, p&lt;0.001). Conclusions: Socially isolated patients with metastatic cancer have inferior survival, which may be influenced by the reduced use of systemic therapy. Increasing patient social support should be explored as a means to improve the uptake of systemic therapy and its benefits on survival in patients with advanced cancer.
Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine
Authors: Jake R. Conway, Eric Kofman, Shirley S. Mo, Haitham Elmarakeby, Eliezer Van Allen
Journal: Genome Medicine (2018)

Abstract Immune checkpoint blockade (ICB) therapies, which potentiate the body’s natural immune response against tumor cells, have shown immense promise in the treatment of various cancers. Currently, tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are the primary biomarkers evaluated for clinical management of cancer patients across histologies. However, the wide range of responses has demonstrated that the specific molecular and genetic characteristics of each patient’s tumor and immune system must be considered to maximize treatment efficacy. Here, we review the various biological pathways and emerging biomarkers implicated in response to PD-(L)1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) therapies, including oncogenic signaling pathways, human leukocyte antigen (HLA) variability, mutation and neoantigen burden, microbiome composition, endogenous retroviruses (ERV), and deficiencies in chromatin remodeling and DNA damage repair (DDR) machinery. We also discuss several mechanisms that have been observed to confer resistance to ICB, such as loss of phosphatase and tensin homolog (PTEN), loss of major histocompatibility complex (MHC) I/II expression, and activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and transforming growth factor beta (TGFβ) pathways. Clinical trials testing the combination of PD-(L)1 or CTLA-4 blockade with molecular mediators of these pathways are becoming more common and may hold promise for improving treatment efficacy and response. Ultimately, some of the genes and molecular mechanisms highlighted in this review may serve as novel biological targets or therapeutic vulnerabilities to improve clinical outcomes in patients.
Cellular phone-based application as a tool in pediatric palliative care.
Authors: MarÃa Sabina Ah Chu SÃ¡nchez
Journal: Journal of Clinical Oncology (2018)

48 Background: Free cross-platform instant messaging is a popular way of communicating in Panama. Is it possible to apply this in Palliative Care (PC)? Methods: This is a descriptive transversal study of some problems we could solve internally with the help of this cell phone-based application. The universe is the total of consultations of the PC Pediatric Support Team in Panamá Children’s Hospital to the National Program of PC from May 2016 to July 2018. First, we developed a chat group, so all 55 members of the national palliative program can share specific information related to PC topics. We describe the most common problems that we can solve with the help of instant messaging technology such as: 1. Presentation of cases at the time of their going-back home from the hospital-team to the community-team. 2. Presentation of urgent cases to the National Aero-Naval Force to be transported by boat or plane. 3. Education of mothers on specific problems they have at home. Results: We had 113 consultations in pediatric palliative care group. Of those, 78% had to be presented to the community-health-care-center (88 cases). The time-of-response was in the range of 5-120 minutes. We had to arrange sanitary transportation by boat or plane in 14% of the cases. Of those cases we obtained a response by the Aero-Naval force in less than 24 hours. We solved specific palliative symptom problems such as: fever, administration of the rescue dose, mucositis, and coping problems in some patients that lived more than two hours from the nearest health-center. For this we used educational videos made for this purpose. Conclusions: Instant messaging technology is used for the provision of palliative care communication, safety transportation and clinical problem solving. It had to be used in conditions that protect the privacy of patients and families. This current study suggest that this is a new opportunity that must be considered for its efficiency in solving specific problems.
Comparative Efficacy and Safety of Daratumumab in Combination with Bortezomib, Melphalan, and Prednisone (D-VMP) in Alcyone Versus Bortezomib, Melphalan, and Prednisone (VMP) in Vista in Newly Diagnosed Multiple Myeloma (NDMM) Patients Using Propensity Score Matching (PSM)
Authors: Michele Cavo, Meletios A Dimopoulos, Jesus F San-Miguel, Maria-Victoria Mateos, Andrzej Jakubowiak, William Deraedt, Annette Lam, Tobias Kampfenkel, Ming Qi, Jianming He
Journal: Blood (2018)
Does use of total parenteral nutrition in patients with metastatic gastrointestinal cancer impact hospice length of stay?
Authors: Jessica J Bian, Rachel S Rome, Angela Marie Taber
Journal: Journal of Clinical Oncology (2018)

58 Background: The use of total parenteral nutrition (TPN) in metastatic cancer patients is controversial. The impact of TPN use on length of hospice stay in advanced cancer patients is unknown. We hypothesize that patients with metastatic gastrointestinal cancers who receive TPN have a shorter median length of hospice stay as compared to the median hospice length of stay for cancer patients in the United States in 2014 (18 days). The primary objective of our retrospective, single-institution study is to determine the median hospice length of stay in patients with metastatic gastrointestinal cancers who received TPN. Methods: Records of all adult patients with metastatic gastrointestinal cancers who received TPN at The Lifespan Cancer Institute from 2005 through 2014 were reviewed. The primary outcome was median hospice length of stay. Data analysis was conducted using Stata (Version 15.0, StataCorp, College station, Texas). Results: Seventy-nine patients were identified as having received TPN for metastatic gastrointestinal cancer. Forty-eight patients had documented referrals to hospice and 40 patients had assessable durations of hospice admission. Hospice length of stay ranged from one to 196 days with a median of 9.5 days, mean of 24.3 days, and interquartile range of 5.5 to 54 days. Conclusions: Hospice care has been shown to improve quality of life for patients and caregivers. In our retrospective, single-institution study of patients with metastatic gastrointestinal cancer who received TPN, the median hospice length of stay was shorter than the national median length of hospice stay for cancer patients in 2014 (9.5 days versus 18 days). This should be taken into consideration when weighing the risks and benefits of initiating TPN in metastatic gastrointestinal cancer patients. [Table: see text]
Uterine Cancer Incidence and Mortality — United States, 1999–2016
Authors: S. Jane Henley, Jacqueline W. Miller, Nicole F. Dowling, Vicki B. Benard, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Uterine cancer is one of the few cancers with increasing incidence and mortality in the United States, reflecting, in part, increases in the prevalence of overweight and obesity since the 1980s (1). It is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among U.S. women (1). To assess recent trends in uterine cancer incidence and mortality by race and ethnicity, CDC analyzed incidence data from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and mortality data from the National Vital Statistics System (2). Most recent data available are through 2015 for incidence and through 2016 for mortality. Uterine cancer incidence rates increased 0.7% per year during 1999-2015, and death rates increased 1.1% per year during 1999-2016, with smaller increases observed among non-Hispanic white (white) women than among women in other racial/ethnic groups. In 2015, a total of 53,911 new uterine cancer cases, corresponding to 27 cases per 100,000 women, were reported in the United States, and 10,733 uterine cancer deaths (five deaths per 100,000 women) were reported in 2016. Uterine cancer incidence was higher among non-Hispanic black (black) and white women (27 cases per 100,000) than among other racial/ethnic groups (19-23 per 100,000). Uterine cancer deaths among black women (nine per 100,000) were higher than those among other racial/ethnic groups (four to five per 100,000). Public health efforts to help women achieve and maintain a healthy weight and obtain sufficient physical activity can reduce the risk for developing cancer of the endometrium (the lining of the uterus), the most common uterine cancer. Abnormal vaginal bleeding, including bleeding between periods or after sex or any unexpected bleeding after menopause, is an important symptom of uterine cancer (3). Through programs such as CDC's Inside Knowledge* campaign, promoting awareness among women and health care providers of the need for timely evaluation of abnormal vaginal bleeding can increase the chance that uterine cancer is detected early and treated appropriately.
Enhancement of Tum-5 antitumor activity by targeted delivery to APN/CD13
Authors: Jieru Meng, Yingqi Zhang, Zhen Yan, Nan Ma
Journal: Cancer Research (2006)

1755  Tumstatin was identified as possessing anti-angiogenic activity. The anti-angiogenic activity of tumstatin was localized to the 54-132-amino acid,Tum-5 domain,and the activity was mediated by αVβ3 integrin interaction in an RGD-independent manner. Human Tum-5 is at least 10-fold more active than human endostatin. NGR motif is the ligand for aminopeptidase N (APN) that is also known as CD13, a marker of angiogenic endothelial cells. NGR peptides have proven useful for delivering various antitumor compounds to tumor vessels. In present research, we synthesized the gene encoding the amino acids 45-132 of tumstatin as Tum-5 which includes the N-terminal 9 amino acids in addition to the previously identified anti-angiogenic domain (54-132 amino acids). The additional 9 amino acids were added to enhance the efficiency of protein expression. Then we coupled a cyclic peptide NGR(-CNGRCVSGCAGRC-) motif to the C terminus of Tum-5(45-132 amino acids) and treated human lung cancer xenograft SPC-A-1 in nude mice. Mice treated with Tum-5-NGR displayed more significant tumor regression, pronounced destruction of the tumor vasculature and induction of tumor and endothelial cells apoptosis than Tum-5 did. We also demonstrated that Tum-5-NGR could selectively accumulate to tumor blood vessels in vivo by using immunohistochemistry. Moreover, anti-angiogenic effect of Tum-5-NGR was also examined in vitro. We demonstrated that Tum-5-NGR could inhibit the invasion, migration and tube formation of HUVEC. In MTT assay, we observed Tum-5-NGR could inhibit the proliferation of HUVEC in a dose-dependent manner. Together, these data indicate that Tum-5-NGR is an effective inhibitor of tumor-associated angiogenesis and a potential candidate for the treatment of cancer.
Association of the Trauma of Hospitalization With 30-Day Readmission or Emergency Department Visit
Authors: Shail Rawal, Janice L. Kwan, Fahad Razak, Allan S. Detsky, Yishan Guo, Lauren Lapointe-Shaw, Terence Tang, Adina Weinerman, Andreas Laupacis, S. V. Subramanian, Amol A. Verma
Journal: JAMA Internal Medicine (2018)

Trauma of hospitalization refers to the depersonalizing and stressful experience of a hospital admission and is hypothesized to increase the risk of readmission after discharge.To characterize the trauma of hospitalization by measuring patient-reported disturbances in sleep, mobility, nutrition, and mood among medical inpatients, and to examine the association between these disturbances and the risk of unplanned return to hospital after discharge.This prospective cohort study enrolled participants between September 1, 2016, and September 1, 2017, at 2 academic hospitals in Toronto, Canada. Participants were adults admitted to the internal medicine ward for more than 48 hours. Participants were interviewed before discharge using a standardized questionnaire to assess sleep, mobility, nutrition, and mood. Responses for each domain were dichotomized as disturbance or no disturbance. Disturbance in 3 or 4 domains (the upper tertile) was considered high trauma of hospitalization, and disturbance in 0 to 2 domains (the lower 2 tertiles) was considered low trauma.The primary outcome was readmission or emergency department visit within 30 days of discharge. The association between trauma of hospitalization and the primary outcome was examined using logistic regression, adjusted for age; sex; length of stay; Charlson Comorbidity Index Score; Laboratory-Based Acute Physiology Score; and baseline disturbances in sleep, mobility, nutrition, and mood.A total of 207 patients participated, of whom 82 (39.6%) were women and 125 (60.4%) were men, with a mean (SD) age of 60.3 (16.8) years. Among the 207 participants, 75 (36.2%) reported sleep disturbance, 162 (78.3%) reported mobility disturbance, 114 (55.1%) reported nutrition disturbance, and 48 (23.2%) reported mood disturbance. Nearly all participants (192 [92.8%]) described a disturbance in at least 1 domain, and 61 participants (29.5%) had high trauma exposure. A statistically significant 15.8% greater absolute risk of readmission or emergency department visit was found in participants with high trauma (37.7%; 95% CI, 25.9%-51.1%) compared with those with low trauma (21.9%; 95% CI, 15.7%-29.7%), which remained statistically significant after adjusting for baseline characteristics (adjusted odds ratio, 2.52; 95% CI, 1.24-5.17; P = .01) and propensity score matching (odds ratio, 2.47; 95% CI, 1.11-5.73; P = .03).Disturbances in sleep, mobility, nutrition, and mood were common in medical inpatients; such trauma of hospitalization may be associated with a greater risk of 30-day readmission or emergency department visit after hospital discharge.
Patient-reported outcomes with metastatic castrate-resistant prostate cancer.
Authors: Jimmy Mullally, Christopher Davella, Rahul Atul Parikh, G J. Van Londen, Leonard Joseph Appleman
Journal: Journal of Clinical Oncology (2018)

207 Background: Prostate cancer accounts for approximately 10% of cancer deaths in men worldwide. Clinical trials for metastatic castrate resistant prostate cancer (mCRPC) have established survival benefit with use of abiraterone (ABI) with prednisone or enzalutamide (ENZ). Despite their wide utilization, little is known about patient quality-of-life (QOL) outcomes for these agents. Our study evaluates patient reported QOL while taking ENZ or ABI/prednisone. Methods: 22 mCRPC patients were enrolled in an open label, nonrandomized manner to receive oral ENZ (n=12) or ABI/prednisone (n=6) per oncologist’s discretion. Patients completed multiple QOL validated questionnaires, including EPIC-26, FACT-P, and FACT-COG at baseline, 1,2,3,6,9 and 12 months or until progression/change of therapy. Surveys were scored by treatment group using mean, median, range, and standard deviations. QOL parameters were compared between the two groups with two-sided, two-sample T test and linear mixed models. Results: Surveys discontinued prior to 1 year secondary to disease progression/change of therapy were 58% and 33% for ENZ and ABI, respectively. By month 3, 50% of surveys were returned for ENZ and 33% for ABI. Month-to-month comparisons of QOL parameters including urinary irritation, incontinence, bowel, sexual, hormonal function, and overall well-being showed no significant differences between treatment groups or different rates of change. Perceived Cognitive Impairment was significantly lower for patients on ABI in month 3, yet Perceived Cognitive Ability favored ENZ in months 2 and 3. All other data points for cognition showed no significant differences. Conclusions: Data from FACT-COG shows discordance in perceived Cognitive Impairment and Abilities between ENZ and ABI in months 2-3. Other QOL domains indicated no difference between the two groups. The study was limited by a significant portion of patients with disease progression/change of therapy. For those on therapy, survey compliance remained high. Thus, the use of questionnaires is a feasible means of assessing patient outcomes and can be adapted to larger studies.
Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity
Authors: Martin Niethammer, Chris C. Tang, An Vo, Nha Nguyen, Phoebe Spetsieris, Vijay Dhawan, Yilong Ma, Michael Small, Andrew Feigin, Matthew J. During, Michael G. Kaplitt, David Eidelberg
Journal: Science Translational Medicine (2018)

Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson's disease (PD). A phase 2 clinical trial showed that delivering glutamic acid decarboxylase (GAD) into the subthalamic nucleus (STN) of patients with PD had therapeutic effects. To determine the mechanism underlying this response, we analyzed metabolic imaging data from patients who received gene therapy and those randomized to sham surgery, all of whom had been scanned preoperatively and at 6 and 12 months after surgery. Those who received GAD gene therapy developed a unique treatment-dependent polysynaptic brain circuit that we termed as the GAD-related pattern (GADRP), which reflected the formation of new polysynaptic functional pathways linking the STN to motor cortical regions. Patients in both the treatment group and the sham group expressed the previously reported placebo network (the sham surgery-related pattern or SSRP) when blinded to the treatment received. However, only the appearance of the GADRP correlated with clinical improvement in the gene therapy-treated subjects. Treatment-induced brain circuits can thus be useful in clinical trials for isolating true treatment responses and providing insight into their underlying biological mechanisms.