tbuckley/cabot-search huggingface dataset:
Emotional distress prior to chemotherapy and delayed nausea in breast cancer patients
Authors: S. C. Higgins, D. H. Bovbjerg, G. R. Morrow, J. A. Roscoe
Journal: Journal of Clinical Oncology (2008)

9527 Background: Delayed nausea following cancer chemotherapy (occurring more than 24 hours post-treatment) is not well controlled by antiemetic medication and remains a widespread problem in clinical practice. Possible modifiable risk factors for delayed nausea are thus an important area for research. Two recent small scale studies with heterogeneous patient samples have raised the possibility that heightened levels of pretreatment emotional distress may be one such risk factor. The present study analyzed a preexisting dataset to test the hypothesis that patients’ levels of emotional distress on the morning of their first chemotherapy infusion would predict the severity of delayed nausea assessed daily following treatment. Methods: Data from women (n=118) with breast cancer (mean age = 52.2 years) treated as outpatients with doxorubicin and standard antiemetics (e.g., 5HT3 agonists) were included in this study. Patients were asked to rate their emotional distress (independent variable) for the morning of their first infusion using a numeric rating scale (0–7). The dependent variable, post-treatment nausea (PTN) was assessed (0–7) over the subsequent 5 days using daily diaries, beginning on the evening of the treatment day. PTN was divided into 2 time periods: acute (within 24 hours after treatment) and delayed (more than 24 hours after treatment). Results: Pretreatment distress had a significant effect on delayed (p<.05), but not acute (p<.06) nausea in multiple regression analyses controlling for demographic and medical variables that preliminary analyses revealed as potential confounders (age, antiemetic use). Confirming the clinical importance of the findings, logistic regression analyses of severe (score ≥6) acute and delayed PTN revealed a significant effect of pretreatment distress on delayed (p<.03), but not acute (p<.10) PTN. Conclusions: The results support the study hypothesis that pretreatment distress is a risk factor for delayed nausea. Further research is warranted to better understand the mechanisms underlying these effects, and to examine the efficacy of pretreatment psychological interventions to reduce delayed nausea in patients receiving chemotherapy for cancer. Support: NCI-U10CA37420. No significant financial relationships to disclose.
Abstract A57: Effects of pre-exposure to siRNA on silencing response: Do cells become resistant to siRNA silencing?
Authors: Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharsky, Nicole Chan, Hasan Uludag
Journal: Clinical Cancer Research (2015)

Abstract Development of resistance against cytotoxic effect of different generations of anticancer drugs is considered inevitable and remains a major concern for cancer therapy. An alternative therapeutic approach based on protein silencing via RNA interference (RNAi) have shown considerable promise; however, our information about the factors affecting siRNA efficiency and the limitations to their efficacy are limited. This study focused on determining the possibility of development of resistance against siRNA treatment as a result of repeated exposure to siRNA that could affect cellular internalization of the particles, silencing efficiency at mRNA level, and ultimately, the observed cellular response. Two approaches to siRNA exposure were undertaken: one involving a single high concentration exposure to eradicate siRNA-responsive cells, and one involving multiple exposures with a gradually increasing siRNA concentration to study the potential intracellular adaptations. Our results demonstrated a temporary decrease in silencing efficiency at mRNA level without significant alteration in siRNA cellular uptake. We conclude that cells would respond to repeated siRNA exposure in a similar fashion after a temporary initial alteration; however, we could not rule out the possibility of a change in phenotypical response (e.g., number of viable cells) as a result of adjustments in (or selection of cells reliant on) alternative pathways. Citation Format: Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharsky, Nicole Chan, Hasan Uludag. Effects of pre-exposure to siRNA on silencing response: Do cells become resistant to siRNA silencing? [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A57.
Dopamine D2 Receptor Activation Causes Mitogenesis via p44/42 Mitogen-Activated Protein Kinase in Opossum Kidney Cells
Authors: VIHANG A. NARKAR, TAHIR HUSSAIN, CARLOS PEDEMONTE, MUSTAFA F. LOKHANDWALA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. This study was conducted to determine the expression of dopamine D2-like receptors in opossum kidney (OK) cells and to examine the potential role of these receptors in mitogenesis. First, the presence of D2-like receptor binding sites in OK cell membranes was demonstrated by radioligand binding, using [3H]spiperone. The D2-like receptor subtypes expressed in OK cells were subsequently demonstrated, by Western blotting, to be D2, D3, and D4 receptors. OK cells were stimulated with bromocriptine, (±)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin hydrochloride, (R)-(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide, or PD 168,077 maleate (D2-like, D2, D3, and D4 receptor agonists, respectively), and mitogenesis was measured as a function of [3H]thymidine incorporation. It was observed that, whereas bromocriptine and (±)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin hydrochloride produced increases in [3H]thymidine incorporation, (R)-(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and PD 168,077 maleate did not produce such an effect, indicating the involvement of D2 receptors in the mitogenic response. Pertussis toxin and PD 98059 blocked the mitogenesis caused by bromocriptine, suggesting a role for Gi or Go proteins and p44/42 mitogen-activated protein kinase (MAPK), respectively. Furthermore, it was observed that bromocriptine produced a time-dependent increase in the phosphorylation (activation) of p44/42 MAPK, which was blocked by domperidone, pertussis toxin, or PD 98059. Therefore, this study demonstrates that, although OK cells express D2, D3, and D4 receptors, activation of only D2 receptors causes mitogenesis via phosphorylation of p44/42 MAPK. Furthermore, the cellular mechanisms contributing to D2 receptor-mediated phosphorylation of p44/42 MAPK seem to involve the tyrosine kinase, phosphatidylinositol-3-kinase, and protein kinase C pathways. It is likely that bromocriptine and other preferential D2 receptor agonists might provide protection against ischemic reperfusion injury in renal proximal tubular cells, by increasing the survival rates for ischemic cells.
Risk factors for febrile neutropenia and the utilization of pegfilgrastim in patients receiving chemotherapy for gynecologic malignancies
Authors: T. M. Numnum, S. Bryant, E. Williams, L. Kilgore, J. M. Straughn
Journal: Journal of Clinical Oncology (2007)

16063 Background: Recently published gudelines for the use of granulocyte-colony stimulating factors define risk factors for the development of febrile neutropenia (FN) in patients receiveing chemotherapy. Our objective is to assess the risk factors associated with FN and the utilization of pegfilgrastim (G-CSF) for the prevention of FN in patients receiving chemotherapy for gynecologic malignancies. Methods: A computerized database identified all outpatient chemotherapy encounters over a 4 month period. Risk factors for FN (adapted from guidelines published by ASCO) were determined for each chemotherapy encounter and a risk factor score was calculated (1–17). Each chemotherapy encounter was analyzed to determine if G-CSF was administered and the reason for utilization. Dose delays/modifications were also determined. Statistical comparisons were performed using the χ 2 test. Results: 692 chemotherapy encounters were identified in 209 patients. 77 % of patients had a diagnosis of ovarian cancer. The mean risk factor score was 3.9 (range 1–9). The most common risk factors were: female (100%), advanced cancer (81%), prior chemotherapy (54%), and age &gt; 65 yo (46%). 276 of the 692 (40%) encounters utilized G-CSF. 135 patients (49%) received G-CSF as primary prophylaxis for the development of FN; 141 patients (51%) received G-CSF after an episode of Grade 3 or 4 neutropenia. The mean risk factor score was 4.3 in patients receiving primary prophylaxis. After primary prophylaxis, 1 dose delay/modification for neutropenia was experienced versus 14 dose delays/modifications without prophylaxis (p &lt;0.01). There were 12 dose delays/modifications due to thrombocytopenia in patients receiving PP. There was only one episode of FN. 64% of patients receiving primary prophylaxis were treated with a docetaxel-containing regimen and 61% of patients were receiving primary chemotherapy. Conclusions: G-CSF is utilized in 40% of chemotherapy encounters and is commonly associated with docetaxel-containing regimens. Dose delays/modifications are uncommon after primary prophylaxis with G-CSF in patients receiving chemotherapy for gynecologic malignancies. No significant financial relationships to disclose.
Long-term follow-up of patients with lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia) who were treated with alemtuzumab.
Authors: J. D. Soumerai, Z. R. Hunter, M. Boxer, B. S. Kahl, L. I. Ioakimidis, C. J. Patterson, S. P. Treon
Journal: Journal of Clinical Oncology (2010)

8109 Background: CD52 is widely expressed on BM lymphoplasmacytic cells and growth supporting mast cells in lymphoplasmacytic lymphoma (LPL). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL (27 IgM; 1 IgA) were enrolled. Baseline characteristics: Median age 60 years; BM involvement 30%; serum Ig 3,510 mg/dL; hematocrit 35%. Median prior therapies was 2 (range 0-5), and 12/28 (43%) had refractory disease. Patients received 3 test doses of alemtuzumab (3, 10, 30 mg IV), then 30 mg IV TIW for up to 12 weeks. Patients received acyclovir and bactrim or equivalent prophylaxis. Results: Responses: CR (n=1); PR (n=9); MR (n=11) for an overall and major RR of 75% and 36%, respectively. Median serum Ig decreased from 3,510 to 1,460 mg/dL; p<0.001 at best response. With a median follow-up of 55 months, the median TTP is 16 months. Hematological toxicities were common among previously treated, but not untreated patients. Grade ≥ 3 toxicities included neutropenia 54%; thrombocytopenia 25%; anemia 11%; rash 11%; infection 7%. CMV reactivation and infection were common among previously treated patients, and etiological for one death. Two other patients succumbed on study, one related in part to complications of drug therapy directed at CMV infection, and another prompted by treatment-related thrombocytopenia in a patient with Von Willebrand's. Long term follow-up revealed late-onset idiopathic thrombocytopenia in 4 patients at a median of 13.6 (range 3.9-24.6 months) following therapy. An important and unexpected finding was the restoration of peripheral blood (PB) CD19+ B lymphocytes, and IgG levels following alemtuzumab therapy (p<0.01 and 0.06, respectively). Conclusions: Alemtuzumab is highly active in patients with LPL. Toxicity was common, particularly among previously treated patients. ITP was observed as a late treatment manifestation. Recovery of CD19+ cells and serum IgG levels suggests that a CD52+ population may be responsible for the PB B-cell lymphopenia and IgG hypogammaglobulinemia commonly observed in LPL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Celgene, Genentech, Millennium Biogen Idec, Celgene, Genentech, Millennium Celgene, Millennium
Comorbidities' impact on survival after treatment for early breast cancer.
Authors: L. H. Land, S. O. Dalton, M. Jensen, M. Ewertz
Journal: Journal of Clinical Oncology (2010)

584 Background: Guidelines for adjuvant treatment of breast cancer are based on results of randomized clinical trials and we apply these guidelines on the general population of women with early breast cancer without taking such comorbidity into consideration. Methods: With the aim of studying comorbidity, we used the Danish Breast Cancer Cooperative Group database to identify all women diagnosed with early breast cancer between 1990 and through 2006. We obtained information on somatic comorbidity and cause of death, by linkage to the national Hospital Discharge Registry and the national Death Registry through the unique personal identification number. Comorbidity was categorized according to the Charlson Comorbidity Index (CCI) score 0, 1, 2 and 3+. Cox proportional hazard regression was performed to determine the hazards of death, breast cancer specific mortality and non-breast cancer mortality, adjusting for: age, stage, year at diagnosis, receptor status, fascial invasion, vascular invasion, type of surgery and treatment. Results: Among 55,139 women, with a median estimated potential follow-up of 7.4 years, 18,537 had died, including 14,076 deaths from breast cancer and 4,461 deaths from other causes. Compared with women with no comorbidity (CCI=0) the risk of dying from breast cancer, as well as other causes, increased significantly with increasing CCI (Table). Conclusions: Having adjusted for other prognostic factors, comorbidity significantly increases risk of dying both from breast cancer and other causes. Hazard ratios with 95% confidence intervals Breast cancer-specific mortality Non-breast cancer mortality All-cause mortality CCI n Adjusted HR 95% CI Adjusted HR 95% CI Adjusted HR 95% CI 0 44,313 1 Reference 1 Reference 1 Reference 1 5,838 1.30 1.23-1.37 1.97 1.81-2.13 1.44 1.38-1.51 2 3,211 1.34 1.25-1.44 2.24 2.03-2.47 1.55 1.47-1.64 3+ 1,777 1.72 1.59-1.88 3.55 3.16-3.99 2.12 1.98-2.27 * All p values < 0.0001. No significant financial relationships to disclose.
Diffuse large B-cell lymphoma (DLBCL) in African American patients: A retrospective study of clinical, molecular, and therapeutic differences in a sample population treated at UAB Comprehensive Cancer Center (UAB CCC)
Authors: A. S. The, V. Reddy, Y. Li, R. Davis, M. Baird, J. M. Foran
Journal: Journal of Clinical Oncology (2007)

21035 Background: SEER registry data indicate African Americans (AA) have a lower incidence of non-Hodgkin's lymphoma (NHL) but face higher lymphoma-specific mortality rates than Caucasians (C). To investigate this we compared outcomes between AA &amp; C patients (pts) with DLBCL treated at UAB CCC. Correlative histologic &amp; molecular studies of established prognostic features were performed to investigate differences. Methods: After IRB approval, DLBCL pts diagnosed '95-'06 were identified from pathology &amp; referral databases. Baseline demographic &amp; clinical data were extracted, including treatment (Rx), response &amp; survival. Expression patterns of CD10, bcl-6, &amp; MUM-1 were used to identify germinal center B-cell-like (GCB) vs non-GCB molecular subtype of DLBCL based on algorithm of Hans et al (2004). HLA-DR, bcl-2, &amp; CD138 expression was determined. A 2:1 age- &amp; gender-matched comparison of C to A pts was performed to evaluate differences. Descriptive analysis with X 2 &amp; Wilcoxon nonparametric tests &amp; Kaplan Meier survival analysis were performed to determine differences. Results: 188 DLBCL patients were identified. Race was noted in 129, including 18 AA pts (14%). In comparison to 36 C pts (2:1 match), no differences were seen in LDH or stage at presentation. AA pts achieved better response to 1st-line Rx (p=0.01) &amp; received fewer regimens (1 vs &gt;1, p=0.05), however they were more likely to receive rituximab with 1st-line Rx (p=0.02), likely reflecting presentation in the post-rituximab era. Median survival, not yet reached for AA's, was 23 months for C pts (p=0.0509). Univariate &amp; parametric survival analyses demonstrated LDH (p=0.0217) &amp; 1st-line rituximab (p=0.0048) independently affected survival. In a separate cohort, no significant difference between races was seen in frequency of GCB vs non-GCB subtype or in expression of bcl-2, CD-138, or HLA-DR. Conclusions: Contrary to SEER observations, the outcome of AA DLBCL pts was superior to C pts in this single center study. No molecular or clinical prognostic feature dominated in either race. The fact that more AA than C patients received rituximab upfront confirms the benefit of adding this agent to 1st-line Rx. No significant financial relationships to disclose.
Relationship between single nucleotide polymorphism of estrogen receptor gene and endocrine therapy efficacy in breast cancer
Authors: X. Yingchun, F. Zhang, H. Wang, Y. Ma, L. Sun
Journal: Journal of Clinical Oncology (2009)

1113 Objective: To explore the distribution of single nucleotide polymorphism (SNP) loci of estrogen receptor (ESR1) gene in breast cancer patients and to study the relationship between the SNP genotypes and the efficacy to endocrine therapy. Methods: Fifteen SNP loci ( rs872921 , rs2077647, rs3904766, rs2234693, rs11155816, rs827419 , rs2347867, rs3798759, rs1801132, rs985191 , rs9340931, rs9397463, rs722209 , rs3778099, and rs3798577) of ESR1 gene were selected as genetic markers. PCR-restriction fragment length polymorphisms, PCR-DNA sequencing and allele-specific real time PCR methods were employed to analyze the loci genotype of 240 patients with breast cancer accepted endocrine therapy. Results: The loci rs872921 and rs3904766 were abandoned for poor ploymorphisms, and the other 13 loci had polymorphisms. The frequencies of alleles and genotypes of rs2077647 and rs3798759 were significantly related with the efficacy of endocrine therapy (p &lt; 0. 05). The linkage disequilibrium and the hapotype analysis showed that there were four linkage disequilibrium blocks in ESR1 gene. They were rs2077647∼rs2234693 (LD1), rs2234693∼rs11155816 (LD2), rs9397463∼ rs722209 (LD3), and rs3778099∼rs3798577 (LD4), and the hapotypes of LD2, LD3, s11155816- rs827419 , and rs2347867- rs1801132 were positively related with the efficacy of endocrine therapy (p &lt; 0. 05). Conclusions: Some of the polymorphisms of ESR1 gene and the haplotypes are positively associated with the endocrine therapy efficacy, and maybe account for predicting the endocrine response in breast cancer. No significant financial relationships to disclose.
Abstract #LB-223: Non-steroidal anti-inflammatory drugs and bladder cancer: A pooled multi-cohort study.
Authors: Sarah Daugherty, Ruth Pfeiffer, Richard Hayes, Michael Leitzmann, Alice Sigurdson, Debra Silverman
Journal: Cancer Research (2009)

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

Background: Several case-control studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with decreased risk of bladder cancer, but few prospective studies have evaluated this association. Methods: We investigated the relationship between self-reported NSAID use and bladder cancer risk in three large prospective cohort studies (NIH-AARP Diet and Health Study, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and U.S. Radiologic Technologist Health Study). The frequency of aspirin and non-aspirin NSAID use one year prior to baseline was ascertained using mailed questionnaires. Study-specific hazard ratios (HR) were estimated using the Cox proportional hazards model with age as the time metric. A meta-analytic estimate was calculated using a random effects model. The Q statistic was used to test for heterogeneity between studies. We then pooled the individual cohort data and jointly analyzed all 508,807 individuals with a total of 2,553 incident bladder cancer cases (2,116 men, 437 women) during a median of 7 years of follow-up time. Results: A statistically non-significant reduction in bladder cancer risk was observed in the pooled analysis for regular use (more than 2 times per week) of non-aspirin NSAIDs compared to no use of non-aspirin NSAIDs (HR= 0.91, 95% CI (0.80-1.04)), after adjusting for smoking status, cigarettes per day, study, gender, aspirin, race, and body mass index. A statistically significant inverse association for regular use of non-aspirin NSAIDs was observed among nonsmokers (HR=0.55, 95% CI (0.38-0.80); p-interaction=0.03), with the strongest inverse association seen with daily use (HR=0.50, 95% CI 0.31-0.80; p-trend=0.01). No association was observed between aspirin use and bladder cancer overall (HR:1.07, 95% CI (0.97-1.19)) or among nonsmokers (HR=1.15, 95% CI (0.88-1.49)). Conclusion: In this pooled analysis, regular use of non-aspirin NSAIDs, but not aspirin, was associated with a significant reduction in risk for bladder cancer among non-smokers.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-223.
Extended linifanib therapy in patients (pts) with advanced hepatocellular carcinoma (HCC) in a phase II trial.
Authors: P. J. Chen, W. Yong, B. I. Carr, T. Sato, Q. Qin, J. Qian, P. J. Ansell, E. M. McKeegan, M. D. McKee, J. L. Ricker, D. M. Carlson, H. C. Toh
Journal: Journal of Clinical Oncology (2011)

e14504 Background: Linifanib (ABT-869) is an orally bioavailable, potent, VEGF/PDGF RTK inhibitor. Activity was observed in a phase II trial of pts with HCC (ASCO 2010, abstr 4038). An exploratory analysis of pts who received linifanib for >48 weeks (wk) is presented. Methods: This open-label, multicenter trial of 0.25 mg/kg linifanib QD in Child-Pugh A (CPA) or QOD in Child-Pugh B pts until progressive disease (PD) or intolerable toxicity, is ongoing. Eligibility criteria include ≤1 prior systemic treatment and ≥1 measurable lesions by CT scan. Assessments included tumor response (RECIST) performed by central imaging; adverse events (AEs) per NCI CTCAE v3.0, and plasma concentration of biomarkers. Results: Of the 44 pts treated, 5 received linifanib for >48 wk (range 340-756+ days [d]). All 5pts had median age (range) 49 yrs (35, 59), were Asian and with ECOG status 0-1; 80% were male. 3/5 pts had prior therapies including thalidomide (2 pts) and capecitabine, doxorubicin and fluorouracil (1 each). Grade 3/4 AEs included hypertension (40%). 1/5 had PR, 3/5 had SD and 1/5 had PD (best tumor response). Pt with PD (per central) remained on treatment based on site assessment of PR. Biomarker data was available from 4 pts: all had decreased plasma cancer antigen (CA) 125 (d 22) and alpha-fetoprotein (AFP; d 56), and increased placental growth factor (PIGF; d 22) from baseline. These biomarkers were evaluated based on prior work with linifanib. Conclusions: In this phase II trial, strong signals of activity including biomarker effects, prolonged SD and confirmed PR were seen in HCC pts treated long term with linifanib. In these 5 pts, chronic linifanib treatment provided prolonged clinical benefit. A global phase III trial of linifanib in pts with advanced CPA HCC is ongoing. Pt BL 1 2 3 4 5 Start dose, mg 15.0 17.5 20.0 12.5 20.0 End dose, mg 12.5 12.5 12.5 5.0 15.0 Best % tumor change from BL in SLD 45.0 37.0 49.0 23.0 25.0 Biomarkers, BL CRP H N N N - PIVKA (MV) L H L L - AFP (MV) L H L L - CA125 H L L H - CYFRA 21.1 L L H L - Biomarkers, d 28 PIVKA N Y N N - Abbreviations: BL, baseline; Y, yes; N, no; H, high; L, low; N, normal; SLD, sum of longest diameter; CRP, C reactive protein; PIVKA, proteins induced by vitamin K deficiency or antagonists;MV, median value; CYFRA, cytokeratin fragment.
In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody
Authors: J Michon, S Moutel, J Barbet, JL Romet-Lemonne, YM Deo, WH Fridman, JL Teillaud
Journal: Blood (1995)