tbuckley/cabot-search huggingface dataset:
RCT of community-based patient assistance to improve breast cancer care.
Authors: N. Bickell, R. Franco, K. Fei, H. Leventhal
Journal: Journal of Clinical Oncology (2010)

6035 Background: Unmet needs may affect breast cancer patients' receipt of adjuvant therapy and quality of life. High quality community-based cancer assistance programs abound that can address women's informational, psychosocial and practical needs. We identified newly diagnosed and operated breast cancer patients' needs and randomized women to high quality community-based assistance programs that can meet those needs vs. usual care. Methods: 263 (88%) women with new breast cancer operated at 8 NYC hospitals participating in the RCT completed the 6 month follow-up survey assessing functional status, treatments received, perceptions and demographics. Based on women's needs, preferred mode of receipt of help, we informed the intervention group of appropriate programs, enabled program connection, and for those unconnected at 2 weeks, identified barriers to connection and reinforced plans to connect. Controls received a pamphlet about breast cancer. Results: On average, women were 56 years old, had completed 14 yrs of school, 28% lived in poverty and 45% were white. Of the 263, 161 (61%) had informational, 145 (55%) psychosocial and 141 (54%) practical needs and 61 (23%) expressed no needs. Only 60(23%) had 1 need, 39 (15%) 2 needs and 103 (39%) 3 needs. There were no significant differences between intervention and control groups in age, education, income, race, physical or emotional functional status (SF12), social support or needs. 27% of women with breast conserving surgery did not get RT (50/182) and 7% of those requiring chemo-or hormonal therapy did not receive it (15/216); there were no treatment differences between intervention and control groups. Of the 202 women expressing one or more needs, 12% had all needs met, 53% had no needs met and 35% had some needs met; there was no difference between intervention and control groups getting needs met. Conclusions: Despite providing information and enabling and tailoring connection to high quality community-based patient assistance programs, there is no difference between intervention and control groups' receipt of adjuvant treatment or receipt of patient assistance. The lack of effect may be due to similar rates of patient assistance use and having needs met in both intervention and control groups. No significant financial relationships to disclose.
Copper (Cu) transporter ATP7B mRNA levels as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil (5FU) plus oxaliplatin combination
Authors: E. Martinez-Balibrea, C. Plasencia, A. Martinez-Cardus, I. Ojanguren, J. L. Manzano, P. Mendez, O. Etxaniz, M. Taron, N. Neamati, A. Abad
Journal: Journal of Clinical Oncology (2005)

9603 Background: Previous studies in yeast and human cell lines have demonstrated that Cu transporter ATP7B can mediate resistance to platinum drugs such as Cisplatin, Carboplatin and Oxaliplatin. ATP7B is a P-Type ATPase (mutated in Wilson’s disease) located in the trans-Golgi network that pumps Cu into secretory compartments. Recent studies have demonstrated a correlation between ATP7B protein and/or mRNA levels and outcome in ovarian cancer patients who were treated with a Cisplatin-based chemotherapy. The aim of this study was to evaluate ATP7B expression in tumors from colorectal cancer patients treated with Oxaliplatin plus 5FU (TTD schedule) and its correlation with the outcome. Methods: Total RNA was obtained from paraffin embedded tissues and real time quantitative RTPCR was used to assess the relative expression of ATP7B. Beta-Actin was used as an endogenous control and placenta RNA as a reference. Results: We analyzed 24 metastatic colorectal cancer patients treated with Oxaliplatin plus 5FU. 62.15% were males; 66.7% colon, 33.3% rectum; median ATP7B mRNA expression levels was 0.27 and was used as a cutoff to separate the patients. 61.5% of patients with mRNA levels lower than the cutoff responded to chemotherapy whereas only 27.3% of those who had high levels of ATP7B responded. Median TTP was 7.45 months for the low expression group and 3.1 months for patients in the high expression group (P=0.04 log-rank test). Conclusions: Our data show the importance of ATP7B gene expression in the outcome of colorectal cancer patients treated with Oxaliplatin. Low levels of expression correlated with better response and TTP. These results can open new pharmacogenetic approaches to individualize chemotherapy in colorectal cancer patients to be treated with or without Oxaliplatin. No significant financial relationships to disclose.
Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression
Authors: Xiao-Min Yu, Renata Jaskula-Sztul, Maria R. Georgen, Zviadi Aburjania, Yash R. Somnay, Glen Leverson, Rebecca S. Sippel, Ricardo V. Lloyd, Brian P. Johnson, Herbert Chen
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Notch1, a transmembrane receptor, has been recently shown to aid in the determination of thyroid cell fate associated with tumorigenesis. This study aimed to investigate the clinical relevance of Notch1 and its role in the regulation of differentiated thyroid cancer (DTC) behavior. Experimental Design: We examined Notch1 expression level and its relationship with clinicopathologic features and outcomes of DTC. Notch1 intracellular domain (NICD) was further characterized both in vitro and in vivo by gain-of-function assays using an inducible system. Results: Notch1 expression levels were downregulated in primary DTC tissue samples compared with contralateral nontumor and benign thyroid tissues. Decreased Notch1 expression in DTC was associated with advanced patient age (P = 0.032) and the presence of extrathyroidal invasion (P = 0.005). Patients with lower Notch1 expression had a significantly higher recurrence rate (P = 0.038). Restoration of NICD in a stably doxycycline-inducible metastatic DTC cell line reduced cell growth and migration profoundly. Using an orthotopic thyroid cancer model, NICD induction significantly reduced the growth of the primary thyroid tumor and inhibited the development of lung metastasis. Serpin peptidase inhibitor, clade E, member 1 (SERPINE1) was discovered by microarray as the most significant gene downregulated by NICD. Further validation showed that the induction of NICD reduced SERPINE1 expression in a dose-dependent manner, whereas restoration of a relative higher level of SERPINE1 was observed with NICD back to minimal level. In addition, SERPINE1 knock-down inhibited DTC cell migration. Conclusions: Notch1 regulates the aggressive phenotypes of DTC, which could be mediated by SERPINE1 inhibition. Notch1/SERPINE1 axis warrants further investigation as a novel therapeutic target for advanced DTC. Clin Cancer Res; 22(14); 3582–92. ©2016 AACR.
Assessing rectal toxicity in a pilot study using intrarectal amifostine and concurrent radiation
Authors: N. L. Simone, B. P. Soule, C. Menard, P. Albert, P. Guion, S. Smith, D. Godette, C. N. Coleman, A. K. Singh
Journal: Journal of Clinical Oncology (2006)

18579 Background: There is evidence that daily intrarectal amifostine can protect rectal mucosa during prostate cancer treatment. Instruments more sensitive than the RTOG score may discriminate small but clinically important reductions in proctitis, however these tools need further evaluation. This study used both the RTOG GI toxicity score and expanded prostate cancer index composite (EPIC), a patient-administered quality of life instrument, to evaluate toxicity. Methods: In this pilot study, patients with localized prostate cancer were given daily amifostine (MedImmune, INC., Gaithersburg, MD) which was placed per rectum 30–45 min before 3D conformal radiation (66–76 Gy in 2 Gy fractions to a volume based on PSA, Gleason score and clinical stage). The first 18 patients enrolled received 1gram of amifostine and the next 12 patients were given 2 grams. Toxicity was assessed at baseline, 5, and 7 weeks during treatment and 3, 6, 12, 18, and 24 months after radiation and amifostine treatment. RTOG grading, an EPIC score and proctoscopic examination were done. The EPIC questionaire is a validated instrument that consists of 50 quality of life questions related to urinary, bowel, sexual and hormonal domains. Two subsets of the bowel domain were used: “bowel function” (BF) targets symptom severity and “bowel bother,” (BB) assesses quality of life subscales. Results: Previously reported results demonstrate a clear trend towards protection from rectal toxicity using 2 gm as compared to a 1 gm amifostine dose. Here, we report that the EPIC-BF and EPIC-BB scores are both highly correlated with the RTOG toxicity score with a pearsons coefficient of 0.98 and 0.97 respectively at a median follow up of 24 mos. There was no significant change in the RTOG GI toxicity score over the course of treatment for either amifostine dose group. There was a statistically significant decrease in EPIC-BF score at 7 weeks (p = 0.04) and the EPIC-BB score showed a trend toward improvement (p = 0.07) at the same time point. The EPIC scores at all other time points were not statistically different from baseline. Conclusions: The EPIC score may be a more sensitive measure to detect acute toxicity associated with prostate cancer treatment but needs further investigation in the acute setting. No significant financial relationships to disclose.
6-PACK programme to decrease fall injuries in acute hospitals: cluster randomised controlled trial
Authors: Anna L Barker, Renata T Morello, Rory Wolfe, Caroline A Brand, Terry P Haines, Keith D Hill, Sandra G Brauer, Mari Botti, Robert G Cumming, Patricia M Livingston, Catherine Sherrington, Silva Zavarsek, Richard I Lindley, Jeannette Kamar
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To evaluate the effect of the 6-PACK programme on falls and fall injuries in acute wards. <b>Design</b>&nbsp;Cluster randomised controlled trial. <b>Setting</b>&nbsp;Six Australian hospitals. <b>Participants</b>&nbsp;All patients admitted to 24 acute wards during the trial period. <b>Interventions</b>&nbsp;Participating wards were randomly assigned to receive either the nurse led 6-PACK programme or usual care over 12 months. The 6-PACK programme included a fall risk tool and individualised use of one or more of six interventions: "falls alert" sign, supervision of patients in the bathroom, ensuring patients' walking aids are within reach, a toileting regimen, use of a low-low bed, and use of a bed/chair alarm. <b>Main outcome measures</b>&nbsp;The co-primary outcomes were falls and fall injuries per 1000 occupied bed days. <b>Results</b>&nbsp;During the trial, 46 245 admissions to 16 medical and eight surgical wards occurred. As many people were admitted more than once, this represented 31 411 individual patients. Patients' characteristics and length of stay were similar for intervention and control wards. Use of 6-PACK programme components was higher on intervention wards than on control wards (incidence rate ratio 3.05, 95% confidence interval 2.14 to 4.34; P&lt;0.001). In all, 1831 falls and 613 fall injuries occurred, and the rates of falls (incidence rate ratio 1.04, 0.78 to 1.37; P=0.796) and fall injuries (0.96, 0.72 to 1.27; P=0.766) were similar in intervention and control wards. <b>Conclusions</b>&nbsp;Positive changes in falls prevention practice occurred following the introduction of the 6-PACK programme. However, no difference was seen in falls or fall injuries between groups. High quality evidence showing the effectiveness of falls prevention interventions in acute wards remains absent. Novel solutions to the problem of in-hospital falls are urgently needed. <b>Trial registration</b>&nbsp;Australian New Zealand Clinical Trials Registry ACTRN12611000332921.
Propensity score matched evaluation of epoetin alfa and darbepoetin alfa utilization in patients with cancer receiving chemotherapy.
Authors: R. A. Bailey, O. Tunceli, J. Singer, J. J. Stephenson, M. Senbetta
Journal: Journal of Clinical Oncology (2011)

e16518 Background: To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC). Additionally, we compared the results observed in the total study population (TSP) with a propensity score matched population (PSMP) to account for potential baseline difference that may affect ESA utilization. Methods: A medical claims analysis was conducted from 1/1/2004-7/31/2009 using the HealthCore Integrated Research Database. Patients were age ≥18 years, newly initiated on EPO or DARB, received ≥2 ESA doses, and had ≥1 claim for cancer and chemotherapy proximate to ESA treatment. Patients with myeloid leukemia, chronic kidney disease, receiving dialysis, or treated with both agents were excluded. Propensity score matching was used to identify similar populations in the EPO and DARB groups. January 2010 wholesale acquisition cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP. Results: In the CRC TSP, 4,921 EPO and 9,173 DARB patients were identified. Mean cumulative ESA doses were EPO: 398,770 units and DARB: 1,508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6,041 and DARB: $7,861 (30% higher cost for DARB). Observed dose ratio (EPO units/DARB mcg) was 264:1. The PSMP analysis identified 4,831 ESA-treated CRC patients in each group that were clinically similar. Mean cumulative ESA doses were EPO: 399,694 and DARB: 1,509 mcg. Mean drug costs were EPO: $6,055 and DARB: $7,863 (30% higher cost for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1. Conclusions: This study of ESA utilization in CRC observed higher drug costs for DARB compared with EPO. The observed cost differences and dose ratios were similar between the total study population and propensity score matched population.
Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.
Authors: C H Pui, J E Rubnitz, M L Hancock, J R Downing, S C Raimondi, G K Rivera, J T Sandlund, R C Ribeiro, D R Head, M V Relling, W E Evans, F G Behm
Journal: Journal of Clinical Oncology (1998)

PURPOSE To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis. RESULTS CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements. CONCLUSION Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.
Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β‐blocker for prevention of variceal rebleeding
Authors: I. Lisanne Holster, Eric T.T.L. Tjwa, Adriaan Moelker, Alexandra Wils, Bettina E. Hansen, J. Reinoud Vermeijden, Pieter Scholten, Bart van Hoek, Jan J. Nicolai, Ernst J. Kuipers, Peter M.T. Pattynama, Henk R. van Buuren
Journal: Hepatology (2015)

Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long‐term endoscopic variceal ligation (EVL) or glue injection + β‐blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child‐Pugh score. Kaplan‐Meier (event‐free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow‐up of 23 months, 10 (29%) of 35 patients in the endoscopy + β‐blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding ( P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long‐term follow‐up this difference diminished (38% vs. 23%; P = 0.121). Conclusions : In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β‐blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. (H epatology 2016;63:581–589)
Chromosomes of a Human Neuroblastoma: A New Case With Accessory Minute Chromosomes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Albert Levan, Georg Manolov, Peter Clifford
Journal: JNCI Journal of the National Cancer Institute (1968)

The chromosomes in a human neuroblastoma were analyzed. The stemline karyotype included 46 chromosomes of normal size and, in most cells, a varying number of minute chromosomes. Most of the normal chromosomes conformed completely to the normal human karyotype, except for one member of pair #2, one extra chromosome in the C group, and one chromosome missing in the D group. The deviating chromosome #2 had a lengthier long arm than normal. The extra chromosome in the C group was one of the smallest chromosomes of this group. Since it deviated from the normal C chromosomes and was sometimes involved in satellite associations with a D group chromosome, it was thought to represent the missing D chromosome. Other D chromosomes also deviated somewhat in appearance, in that their short arms were too large. An idiogram of the tumor stemline was constructed from measurements of all chromosomes of 11 cells. The minute chromosomes were evidently centric. Their mitotic behavior, however, was irregular, as evidenced by their wide variation in number between cells (0–58 per cell, average 7.9). Certain similarities between these minutes and accessory chromosomes (B chromosomes) of natural organisms are pointed out.
Activation of monocyte-mediated tumoricidal activity in patients with acquired immunodeficiency syndrome.
Authors: E S Kleinerman, L M Ceccorulli, L A Zwelling, T Twilley, R B Herberman, J Jacob, E P Gelmann
Journal: Journal of Clinical Oncology (1985)

The purpose of these studies was to determine whether peripheral blood monocytes from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma could be activated to lyse human tumor target cells in vitro. Monocytes were isolated and incubated for 24 hours in vitro with either medium (control), a crude mitogen-induced lymphokine preparation (MAF), or endotoxin before the addition of [125I]IUdR-labeled A375 melanoma target cells. Cytolysis was determined 72 hours later. Twelve (100%) of 12 patients tested had monocyte-mediated cytotoxicity values that were comparable to those of normal individuals. Recombinant human gamma interferon (IFN gamma) activated both normal and AIDS monocyte-mediated tumoricidal function only when combined with lypopolysaccharide (LPS). In addition, mononuclear cells from ten AIDS patients were also tested for their ability to secrete MAF and IFN gamma in response to a mitogenic stimulus. Lymphokines generated from all ten patients contained substantial amounts of IFN gamma (100 to 2,500 U/mL); however, three of these ten lymphokine preparations failed to activate normal monocytes to lyse tumor cells. These results suggest that monocyte-mediated tumoricidal function of AIDS patients is intact and thus suggest new approaches for the therapy of AIDS.
Targeting CD123 in acute myeloid leukemia using a T-cell–directed dual-affinity retargeting platform
Authors: Muneera Al-Hussaini, Michael P. Rettig, Julie K. Ritchey, Darja Karpova, Geoffrey L. Uy, Linda G. Eissenberg, Feng Gao, William C. Eades, Ezio Bonvini, Gurunadh R. Chichili, Paul A. Moore, Syd Johnson, Lynne Collins, John F. DiPersio
Journal: Blood (2015)
PITX2: a master regulator of cardiac channelopathy in atrial fibrillation?
Authors: Na Li, Dobromir Dobrev, Xander H.T. Wehrens
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Pitx2c increases in atrial myocytes from chronic atrial ﬁbrillation patients enhancing I Ks and decreasing I Ca,L’ by M. Perez-Hernandez et al. , pp. 431–441. 

This editorial refers to ‘Pitx2 impairs calcium handling in a dose-dependent manner by modulating Wnt signalling’ by E. Lozano-Velasco et al. , pp. 55–66. 

The pathogenesis of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, involves multiple factors including dysfunction of a variety of ion channels, dysregulation of calcium handling proteins, developmental defects, etc.1 Emerging evidence has shown that genetic factors can increase the risk of AF. For example, genome-wide association studies (GWASs) have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with AF.2–5 Among these AF-associated SNPs, two (rs2200733 and rs10033464) located on chromosome 4q25 are most significant and have been repeatedly found in AF patients of various ethnicities.2–4

It has been postulated that these 4q25 variants can increase AF susceptibility by modulating the activity of paired-like homeodomain transcription factor 2 (PITX2), since they are located in the vicinity (∼150 000 bp) of the cis -regulatory region of PITX2.2–4 Consistently, independent groups have demonstrated that the deficiency of PITX2c (the cardiac-specific isoform) predisposes to AF development in mice.6,7 However, it remains controversial whether and how human 4q25 variants regulate PITX2 transcription and whether the level of PITX2 is affected in AF patients.

Previous experimental work has revealed that …