tbuckley/cabot-search huggingface dataset:
Team sugar: Blood glucose screening in acute lymphoblastic leukemia patients during induction.
Authors: Mary C. Shapiro, Titilope Adenike Ishola, Paibel Ixia Aguayo-Hiraldo, Daniel Landi, Kiranmye Reddy, Mehmet Fatih Okcu, Julienne Brackett
Journal: Journal of Clinical Oncology (2017)

57 Background: Pediatric acute lymphoblastic leukemia (ALL) protocols currently include steroids during induction therapy, which may lead to hyperglycemia. Published pediatric and adult leukemia data demonstrate increased rates of infection and mortality associated with hyperglycemia. Presently, there are no accepted recommendations for how to track blood glucose (BG) levels, so hyperglycemia may go undetected. A random review of 20 patients diagnosed with ALL during a 4-month period in 2014 at Texas Children’s Cancer Center (TXCCC) demonstrated that only 40% had BG checked throughout induction. The SMART aim of this quality improvement project was to increase BG screening rates to &gt; 95% during first week of treatment and induction days 8, 15, 22 and 29 for patients with newly diagnosed ALL at TXCCC in a 15-month period. Methods: PDSA cycle 1 involved sticker reminders on treatment roadmaps by days that required a BG check. PDSA cycle 2 entailed reminder flyers in patient care areas and no further roadmap stickers. Primary outcome measure was the percentage of successful occurrences for BG checks on days 8, 15, 22, 29. Secondary outcome measure was the percentage of patients who needed insulin therapy. Results: TXCCC had 97 new ALL patients during March 2015 to May 2016. Providers obtained 333 of 372 possible BG checks (90%) on days 8, 15, 22, 29. Thirty-nine percent of patients developed hyperglycemia ≥ 200 mg/dL. Eighteen percent patients required insulin therapy. Eighty-nine percent of patients had their peak blood glucose by day 8, and 82% of patients who required insulin were started on insulin prior to day 8. Conclusions: We improved hyperglycemia screening rates for TXCCC ALL patients in induction from 40% to 90% by implementing reminder processes for providers. The roadmap stickers were replaced with reminder flyers for sustainability. Because the peak BG was reached by 89% of patients by day 8 of therapy, our efforts are now being directed at improving screening and interventions prior to day 8. Our goal is to standardize BG screening and hyperglycemia intervention algorithms to decrease both the time-to-initiation for insulin and readmission rate for symptomatic hyperglycemia for ALL patients at TXCCC.
An educational tool as an aid for making decisions about the initial treatment of gastric cancer.
Authors: Peter Ravdin, Lindsay Peterson, Julie Rowe
Journal: Journal of Clinical Oncology (2012)

e14684 Background: Tools for making individualized numerical estimates of outcomes and to provide useful information are revolutionizing medicine. We have produced such a tool for decision making for patients with gastric cancer [GC] for whom neo/adjuvant therapy might be an option to be considered. Methods: We widely reviewed the medical literature and meta-analyses about adjuvant and neoadjuvant treatment for potentially resectable [GC]. We also reviewed the guidelines' statements about what is considered appropriate treatment for patients. In addition we used information about individual prognosis based on information from the SEER registry, the AJCC, and also as supplemented from the medical literature. Results: Examination of the medical literature shows the value of adjuvant chemotherapy and radiation for [GC]. For example, and recent GASTRIC meta-analysis of 31 trials found that a benefit for overall survival (hazard ratio [HR], 0.82; 95% CI, 0.76-0.90) and for disease-free survival (HR, 0.82; 95% CI, 0.75-0.90). There is also a substantial literature supporting the use of these regimens in the neoadjuvant setting (such as the MAGIC study with benefit in overall survival (HR for death, 0.75; 95% CI, 0.60 to 0.93). We found however that these HRs were rarely accompanied with estimates of absolute benefit. A typical quote from the GASTIC analysis is "Five-year overall survival increased from 49.6% to 55.3% with chemotherapy," which reflects the outcomes for an average patient. This information is implied as the basis for treatment recommendations for treatment, but numerical estimates of what is gained are not given in such texts as the NCCN guidelines. Our analysis of the SEER data showed disease specific [GC] mortality at 3 years to range from 4% for patients with low grade stage 1a disease to 49 % for patients with high grade stage IIIa disease. Conclusions: Integrating the information about the base line risks for negative outcome with hazard ratio estimates of the effective therapy we can make individualized estimates of outcome. We have also included in the tool substantial additional information about the nature of the disease, past and ongoing trials, and the safety and efficacy of the treatment opinions.
Recruitment of cancer patients to National Institute for Health research cancer research network portfolio studies between 2001 and 2011.
Authors: Matthew Cooper, Karen Poole, David A. Cameron, Robert Haward, Peter John Selby, Richard S. Kaplan, Mahesh Parmar, Rachel Moser, Matthew T. Seymour
Journal: Journal of Clinical Oncology (2012)

6091 Background: The National Institute for Health Research Cancer Research Network (NCRN) was established in 2001 in England, United Kingdom to improve cancer patient outcomes by improving the coordination, integration and speed of cancer research. Methods: Baseline recruitment of cancer patients in England to clinical studies was around 4% of incident population. Research Networks were established initially in England (NCRN) and then across the UK, co-terminus with clinical cancer service networks, and a per capita based funding model used to provide a research infrastructure to support recruitment to a nationally defined research portfolio. Results: Within 3 years, as the networks were established, recruitment of patients to studies doubled from 10,000 to 20,000 cancer patients per year. Recruitment has continued to increase year on year, supported initially by underspend that had accrued from earlier years in the life of NCRN, and more recently from additional resources invested via the NIHR comprehensive networks. Data for 2010/11 show that over 45,000 cancer patients are now recruited into portfolio studies in England each year, with over 50,000 across the whole of the UK. Conclusions: Dedicated, targeted, clinician-led National Health Service investment into supporting national portfolio studies, has delivered an unprecedented five-fold increase in recruitment of cancer patients into clinical trials across the United Kingdom. This required coordinated research infrastructure, close cooperation with research funders, particularly Cancer Research UK and the National Cancer Research Institute, and the enthusiasm and hard work of many clinicians, patients and others working to deliver clinical cancer care in the National Health Service in the United Kingdom.
Experience and impact of alopecia in patients (pts) with HER2+ metastatic breast cancer (MBC) in the SystHERs registry.
Authors: Ginny Mason, Musa Mayer, Sandra M. Swain, Peter Kaufman, Debu Tripathy, Sara A. Hurvitz, Joyce O'Shaughnessy, Denise A. Yardley, Adam Brufsky, Hope S. Rugo, Melody A. Cobleigh, Laura Kay Chu, Vincent P. Antao, Anne Morris, Bongin Yoo, Mohammad Jahanzeb
Journal: Journal of Clinical Oncology (2017)

239 Background: Although alopecia is common with systemic chemotherapy, its psychological impact is often overlooked in treatment (tx) decisions. We sought to better understand the impact of alopecia using data from SystHERs, an observational registry of pts with HER2+ MBC. Methods: SystHERs enrolled pts ≥ 18 years within 6 mos of an MBC diagnosis. Pt-reported outcomes are assessed quarterly. The Alopecia Patient Assessment (APA, Genentech) is a validated instrument measuring the incidence of hair loss in the prior 3 mos and the impact of hair loss in the prior 7 days. The APA includes 5 items scored on a 5-point scale (total range: 1–25). Higher scores indicate greater impact. Pts completed the APA within 30–90 days of initial MBC tx. Subgroups with no hair loss, hair loss without impact, or impactful hair loss were compared descriptively. Results: As of June 3, 2016, 591 of 976 pts were eligible for this analysis. Of these, 175 (30%) reported no hair loss, 123 (21%) reported hair loss without impact, and 293 (50%) reported impactful hair loss within 30–90 days of initial MBC tx. Respectively, 23% (41/175), 82% (101/123), and 79% (231/293) were on active chemotherapy, most commonly docetaxel (39% [16/41], 66% [67/101], and 62% [144/231]) and paclitaxel (5% [2/41], 27% [27/101], and 23% [54/231]). Median time from initial chemotherapy tx to APA was 55, 70, and 64 days. Of all pts with no hair loss, 39% had de novo MBC vs 56% of pts with hair loss but no impact and 55% with impactful hair loss. Relative to the no-hair-loss and hair-loss-but-no-impact subgroups, the subgroup with impactful hair loss was younger (median 57 and 59 vs 54 years, respectively) and had more pts with ≥ 2 metastatic sites (51% and 54% vs 63%) and visceral metastases (59% and 63% vs 69%). The median total APA score for pts with impactful hair loss was 8.8 (IQR 7.0–12.5). Conclusions: Of pts reporting hair loss, 79–82% were receiving systemic chemotherapy. Pts with impactful hair loss may have had greater disease burden. Alopecia impacted self-image and embarrassment more than work or social functioning. Clinical trial information: NCT01615068. [Table: see text]
Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2
Authors: Oscar Rubio Cabezas, Sarah E. Flanagan, Horia Stanescu, Elena García-Martínez, Richard Caswell, Hana Lango-Allen, Montserrat Antón-Gamero, Jesús Argente, Anna-Marie Bussell, Andre Brandli, Chris Cheshire, Elizabeth Crowne, Simona Dumitriu, Robert Drynda, Julian P Hamilton-Shield, Wesley Hayes, Alexis Hofherr, Daniela Iancu, Naomi Issler, Craig Jefferies, Peter Jones, Matthew Johnson, Anne Kesselheim, Enriko Klootwijk, Michael Koettgen, Wendy Lewis, José María Martos, Monika Mozere, Jill Norman, Vaksha Patel, Andrew Parrish, Celia Pérez-Cerdá, Jesús Pozo, Sofia A Rahman, Neil Sebire, Mehmet Tekman, Peter D. Turnpenny, William van’t Hoff, Daan H.H.M. Viering, Michael N. Weedon, Patricia Wilson, Lisa Guay-Woodford, Robert Kleta, Khalid Hussain, Sian Ellard, Detlef Bockenhauer
Journal: Journal of the American Society of Nephrology (2017)

Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic β cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2 We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.
Resource optimisation at a clinical counselling facility for hereditary breast cancer: Why do eligible patients decline result disclosure following BRCA1 gene analysis?
Authors: T. M. Wagner, R. Kroiss, V. Korn, D. Bikas, C. Fürhauser, D. Scheichl, E. Kubista, C. Zielinski, P. Oefner
Journal: Journal of Clinical Oncology (2004)

9597 Background: In Austria, molecular-genetic testing for BRCA1 and BRCA2 is conducted in a clinical setting but financed via research funds. To ensure the optimal use of limited resources, we determined the number of patients who declined to learn their BRCA1 test result after initially opting for molecular-genetic testing. Our report investigates these patients' characteristics and motives. Methods: The study included 552 patients from 280 families eligible for molecular-genetic testing. It was evaluated if patients, after pre-test counselling, decided for or against genetic testing, respectively if they opted for or against result disclosure following genetic testing. Socio-demographic, clinical, and family-related data were used as predictors for patients' decision. Motives for declining result disclosure were assessed by a custom-designed questionnaire. Results: Test result disclosure was declined by 107 patients (19%). Twelve percent of decliners (n = 13) opted for result disclosure after receiving the questionnaire. Male patients (OR = 4.24, P < .001) and patients who underwent abbreviated counselling (OR = 3.73, P < .001) were less likely to opt for disclosure. The same tendency applied to patients without daughters (OR = 1.51, P = .08). Motivational analysis revealed that some patients decided against result disclosure owing to their current distressed life situation. Conclusions: For men and patients without daughters, pre-test counselling should include a particularly thorough investigation of the motives underlying the decision for BRCA testing. Patients declining result disclosure owing to their distressed life situation should be actively contacted again later. An abbreviated pre-test counselling session appears inadvisable. No significant financial relationships to disclose.
Abstract #4463: Targeted imaging of prostate cancer: the smart-bomb pro-drug delivery mechanism
Authors: John Sedelaar, John Isaacs, Samuel Denmeade
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction . Contrast enhanced TRUS, multimodality 3T MRI and nuclear bone scans are the most advanced imaging modalities used in contemporary urological practice for the diagnosis and staging of prostate cancer. All of these imaging modalities may be considered prostate imaging modalities, not prostate cancer imaging modalities. With an increasing number of patients with minimal prostate cancer and opting for either focal treatment or active surveillance, the need for accurate tools for diagnosis and follow-up is eminent. We present our initial experience with two prostate cancer specific imaging pro-drugs. The core of these drugs is thapsigargin, a non-specific highly cytotoxic agent. A tyrosine ring is added for the coupling of imaging probes. The pro-drugs are inactivated due to the binding of a specific amino acid sequence, which can be clipped off by either PSMA or PSA proteases. The resulting activated free-drug is taken up by the prostate cancer cells, resulting in a dual smart-bomb effect of targeted prostate cancer specific imaging and treatment. Materials and methods . Imaging pro-drugs: JHD-9783 (PSMA) and JHD-9784 (PSA) were designed on the basis of 2 therapeutic pro-drugs: G202 (PSMA) and G114 (PSA). The difference between the 2 groups is the addition of a tyrosine ring for imaging probe linking (125I). For characterization of the drugs, MTT and protease-cleavage experiments were performed on LNCaP cell cultures. HPLC and LC-MS were used to analyze different cleavage metabolites. Standard electrophilic iodination chemistry was performed to iodinate the drugs with cold NaI and hot Na125I. SPECT-CT imaging experiments were performed on nude mice bearing LNCaP, LAPC4 or CWR-22R-H subcutaneous tumors. Results . MTT results showed a slightly reduced cell kill for JHD-9783 and JHD-9784, in comparison to G202 and G114. The IC50 for JHD-9783 was 10uM, for JHD-9784 2.5uM. LC-MS analysis showed that LNCaP cells cleaved the PSMA and the PSA pro-drugs into respective free-drug version. The free-drug was found in the cells, and to a lesser degree in the cell media. SPECT-CT imaging of the tumor bearing mice showed uptake by tumors, together with uptake by thyroid, liver and spleen. The PSMA imaging drug was also detectable in the kidneys and bladder. No toxicity was noted. Conclusion . In this study we present our initial experience with 2 prostate cancer targeted imaging drugs. By using the specific protease activity of PSA and PSMA, an inactivated pro-drug is activated in a free-drug and taken up by the cell, resulting in a dual effect of targeted imaging and therapy for prostate cancer. Initial imaging results showed tumor uptake, but also non specific uptake by different organs. Future experiments will address that problem.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4463.
A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma
Authors: Yujie Huang, Prajwal Rajappa, Wenhuo Hu, Caitlin Hoffman, Babacar Cisse, Joon-Hyung Kim, Emilie Gorge, Rachel Yanowitch, William Cope, Emma Vartanian, Raymond Xu, Tuo Zhang, David Pisapia, Jenny Xiang, Jason Huse, Irina Matei, Hector Peinado, Jacqueline Bromberg, Eric Holland, Bi-sen Ding, Shahin Rafii, David Lyden, Jeffrey Greenfield
Journal: Journal of Clinical Investigation (2017)

Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-β and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas.
HMG CoA reductase inhibitors and the risk of colorectal cancer
Authors: J. N. Poynter, G. Rennert, J. D. Bonner, H. S. Rennert, J. K. Greenson, S. B. Gruber
Journal: Journal of Clinical Oncology (2004)

1 Background: 3-hydroxy-2-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors are effective lipid-lowering agents that also inhibit the growth of colon cancer cell lines and were noted to be associated with a reduced risk of colorectal cancer (CRC) in a randomized clinical trial of patients with myocardial infarction. We investigated the association between HMG CoA reductase inhibitors and CRC in a population-based case-control study of incident CRC. Methods: The Molecular Epidemiology of Colorectal Cancer Study (MECC) is a study of 1608 CRC cases diagnosed in northern Israel between 1998 and 2002, and 1734 population-based controls matched for age, gender, and ethnicity. Subjects participated in an interview which assessed personal and family history of cancer, screening practices, other medical conditions, medication use, physical activity, and nutritional data including a food frequency questionnaire. Diagnosis of colorectal cancer was confirmed by standardized pathology review. Use of HMG CoA reductase inhibitors was measured by self report as a dichotomous variable with a minimum duration of five years of use. Results: Use of HMG CoA reductase inhibitors was reported by 267/3342 subjects in the MECC study (7.99%). The unadjusted odds ratio for use of any HMG CoA reductase inhibitor had a significantly protective effect with an odds ratio of 0.46 (95% CI 0.35–0.60). This association remained unchanged (OR 0.49, 95% CI 0.36–0.68) after adjustment for age, hypercholesterolemia, ethnicity, aspirin or NSAID use, and the low penetrance susceptibility allele, APC I1307K. To assess whether the association was the result of a non-specific cholesterol lowering effect, we also looked at other cholesterol-lowering drugs and found no significant association between bezafibrate and CRC (OR 1.08, 95% CI 0.56–2.08). Conclusions: HMG CoA reductase inhibitors are associated with a 51% reduction in the risk of colorectal cancer, and the protective effect is specific to this class of lipid-lowering agents. The significant protective effect of HMG CoA reductase inhibitors in CRC indicates that these drugs deserve further investigation in chemoprevention and therapeutic clinical trials. No significant financial relationships to disclose.