tbuckley/cabot-search huggingface dataset:
Patient and family caregiver perceptions of a cancer-related in-home Reiki experience.
Authors: Hossam Alhawatmeh, Yea-Jyh Chen, Rosanne M. Radziewicz
Journal: Journal of Clinical Oncology (2017)

174 Background: Complementary care modalities are needed for residential patients and family caregivers, in addition to traditional cancer treatments, to effectively alleviate associated symptoms. Reiki is one of the biofield energy modalities which is generally known to provide non-invasive, non-pharmacological, and beneficial relaxation. It has been commonly practiced to cancer patients in clinical and cancer support facilities. However, little is known about providing Reiki at home especially by informal caregivers. This study aims to describe and understand the perceptions of an in-home Reiki practice as experienced by patients with cancer and their family caregivers. Research Question: What are the perceptions of patients and caregivers of their experiences with an in-home Reiki practice? Methods: A descriptive phenomenological approach (Husserl) was used to explore the perceptions of cancer patients and family caregivers of an in-home Reiki practice through narratives of six dyads of participants; six patients with active cancer and six family caregivers were interviewed. Participants were recruited at three sites in Northeast Ohio. Participants’ narratives were analysed according to Colaizzi’s thematic analysis method. Bracketing, peer debriefing, and external audits were performed to enhance the trustworthiness of findings. Results: Seven major themes were identified: 1) exchange of emotional energies, 2) sensory experiences of energy exchange, 3) physical symptom relief, 4) detachment from stressful circumstances, 5) restoration of spiritual wellbeing, 6) recognition of a valued technique, and 7) lifestyle accommodation. Conclusions: Study participants perceived that in-home Reiki was a beneficial self-care practice that improved the health of patients with cancer. An understanding of patient and caregiver perceptions of Reiki practice in home settings may lead to the development of stand practice and guidelines for a successful patient–caregiver intervention, suitable for a daily schedule or lifestyle. Further study is needed to understand the process underlying in-home Reiki in connection with health outcomes related to cancer.
Use of gene set analysis (GSA) for molecular classification of responders and nonresponders to FOLFOX therapy in colorectal cancer (CRC).
Authors: Stephen Yip, Maggie Chon U. Cheang, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2012)

3628 Background: Folinic acid (FOL) fluorouracil (F) and oxaliplatin (OX) chemotherapy is a commonly used therapy for CRC. Lacking in current literature are clinically relevant classifiers for potential responders. GSA technique is statistical method that detects significance of sets of genes, instead of examining a gene-by-gene basis. The objective of this study was to identify differential functionally annotated gene expression profiles associated with response to FOLFOX therapy in CRC tumors using gene-by-gene and GSA approaches. Methods: Genome wide expression profile data were collected on pre-treatment tumor tissues from patients with unresectable CRC receiving FOLFOX therapy (n = 83, Affymetrix HG U133A, GSE28702, Tsuji et al. BJC 2012). Gene expression was compared between responders (n = 42) and Non-responders (n = 41). GSA was conducted on 3272 curated gene sets from the Molecular Signatures Database (Subramanian, Tamayo et al. 2005, PNAS 102, 15545-15550) annotated by biological pathway, biochemical function and clinical behavior. Significant analysis of Microarray (SAM) and GSA (Tibshirani et al.) was done to identify gene sets associated with FOLFOX response. Results: Differential expressions of 23 genes were significantly associated with response, based on a single gene approach (p-value &lt; 0.05). 13 of these were located on Chromosome 17 (p &lt; 0.001). Among these, the top 5 ranked genes included NPEPPS, MBTD1, CEP44, LTA4H and CPNE4 which are involved in metal ion binding and aminopeptidase activity. GSA revealed only 44 out of 3272 gene sets were significantly associated with response, with a false discovery rate less than 25%. Increased expression of B-lymphocyte differentiation and Ras-signalling-related gene sets was associated with responders while mTOR signaling and hematopoietic stem cell-related genes set were associated with non-responders. Conclusions: Our data showed that differential biological pathways could be identified to predict response to FOLFOX therapy for CRC patients. Analysis may be useful to help define clinically relevant biologic subtypes among patients with metastatic colorectal cancer.
A preoperative model evaluating the tissue effects of chemopreventive agents in low-volume prostate cancer
Authors: J. Kim, X. Wang, R. Babaian, L. Pisters, C. Pettaway, C. Wood, A. Sabichi, T. McDonnell, C. Logothetis, P. Troncoso
Journal: Journal of Clinical Oncology (2006)

1007 Background: To identify and assess biomarkers modulated by prostate cancer chemopreventive agents, we created a model that, by exploiting the time between histologic diagnosis of prostate cancer and definitive therapy (prostatectomy), expedites tissue cross comparison and confronts the multifocality and multizonal heterogeneity of prostate cancer. Methods: Between February 2001 and April 2002, 48 presurgical patients were enrolled in a single-institution, randomized, double-blind trial of vitamin E (VE) and L-selenomethionine (SeMET) based on the framework of the ongoing Selenium and Vitamin E Cancer Prevention Trial. Patients were treated with 400 IU VE, 200 μg SeMET, a combination of VE and SeMET, or placebo for 3 to 6 weeks before prostatectomy. All patients also received a multivitamin and vitamin C 250 mg each day. Ex vivo simulated sextant biopsies on the radical prostatectomy specimen (RPS) were performed, and 36 of 39 evaluable patients had RPS sections that were suitable for pathologic evaluation. Blood components were collected at baseline and prior to prostatectomy. We derived an apoptotic index (AI) morphologically and a proliferation index (PI) by using immunohistochemistry and counting Ki-67-positive nuclei. Cells were counted and identified by cell type (normal and cancerous) and by zone (peripheral [PZ], transition [TZ], and central [CZ]). Results: In normal epithelial cells when the Wilcoxon rank sum test was used to compare AI and PI changes between groups, the AI was higher in the TZ than in the CZ, a difference independent of treatment effects (p = .01). Between the largest PZ and TZ tumor foci, a statistically significant difference in PI was observed (p = .006). Using a multiple linear regression model fitted for AI from the largest RPS PZ tumor focus, we found a statistically significant difference between the SeMET group and the placebo group (p = .02). Conclusions: Besides introducing new findings, the clinicopathologic model proved itself a platform for biomarker discovery by leveraging molecular technologies to full advantage, including serum protein profiling (Kim et al., CEBP 2005) and gene expression profiling of different cell types. Supported by NIH grant CA88761. No significant financial relationships to disclose.
Precision delivery of RAS-inhibiting siRNA to pancreatic cancer via peptide-based nanoparticles.
Authors: Matthew S. Strand, Hua Pan, Bradley Krasnick, Xiuli Zhang, Peter S. Goedegebuure, Timothy Fleming, David G DeNardo, William E. Gillanders, William G. Hawkins, Samuel A. Wickline, Ryan C. Fields
Journal: Journal of Clinical Oncology (2017)

287 Background: Greater than 95% of pancreatic adenocarcinomas (PDACs) are driven by KRAS activation; yet, despite decades of work, no RAS inhibitors have reached the clinic. Furthermore, the delivery of therapeutic agents of any kind to PDAC has been hindered by the extensive desmoplasia that accompanies these tumors. Herein, we show that serum-stable and pH-sensing nanoparticles (NPs) are taken up by PDAC cells, can deliver KRAS-specific siRNA into the cytoplasm and inhibit KRAS expression, thereby causing cell death. We go on to use a spontaneous model of pancreas cancer to show that this system can effectively deliver siRNA to stroma-rich tumors. Methods: The murine PDAC cell line KP1 was tested for NP uptake in vitro utilizing fluorescent siRNA NPs (fNPs) in combination with confocal microscopy and flow cytometry. KP1 cells were treated with KRAS-siRNA NP, and KRAS expression and cell viability were assessed with RT-PCR and CellTiter-Glo, respectively. Mice bearing subcutaneous KP1 tumors and KPPC mice with spontaneous PDAC were injected with fNP, and tumor fluorescence was assessed using an in vivo imaging system and fluorescence microscopy. Results: KP1 cells take up fNP in vitro, with &gt; 99% of cells positive for fluorescent signal at 24 hours. Treatment with KRAS-siRNA NP of KP1 cells reduced KRAS expression by 69% (see Figure) and reduced cell viability by 45% compared to untreated and scramble-siRNA treated controls. Gemcitabine demonstrated an additive effect with anti-KRAS therapy. Tumors from KP1 cells grown in mice, and tumors from KPPC mice, were strongly fluorescent 24 hours after IV injection of fNP. Fluorescence microscopy showed successful delivery of fNP to tumors. Conclusions: Our NP system can precisely deliver siRNA to KP1 cells and spontaneous PDAC, overcoming the predominant stromal component in these tumors. KRAS-siRNA delivery downregulates KRAS expression, leading to cell death. This represents a novel treatment for PDAC. Furthermore, with its ability to deliver siRNA into the tumor microenvironment and suppress a known oncogene, this platform could be used to target other putative drivers of tumor progression across various cancer types.
Preclinical antitumor activity of nanoliposomal irinotecan (Nal-IRI, MM-398) and utilization as a foundation of front-line pancreatic cancer regimens.
Authors: Daniel F. Gaddy, Helen Lee, Nancy Paz, Shannon C. Leonard, Ashish Kalra, Ninfa L. Straubinger, Robert M Straubinger, Bryan M. Gillard, Michael T. Moser, Barbara A. Foster, Daryl C. Drummond, Stephan G. Klinz, Bart Hendriks, Jonathan B. Fitzgerald
Journal: Journal of Clinical Oncology (2017)

336 Background: Nanoliposomal irinotecan (nal-IRI, MM-398) recently gained approval in combination with 5-fluorouracil/leucovorin (5-FU/LV) in post-gemcitabine metastatic pancreatic ductal adenocarcinoma (PDAC) based on the extended survival and manageable safety profile observed in the Phase 3 NAPOLI-1 trial. Preclinically, we have previously demonstrated the anti-tumor activity of nal-IRI with 5-FU and oxaliplatin, standard of care agents in first-line PDAC, and are currently investigating this combination in patients with previously untreated metastatic PDAC in a Phase 2 clinical trial (NCT02551991). Herein, we further evaluate nal-IRI as a potential backbone of first-line metastatic PDAC by assessing the preclinical anti-tumor activity of nal-IRI relative to, and in combination with, gemcitabine and nanoparticle albumin-bound-paclitaxel (nab-P). Methods: Nal-IRI tumor metabolite (CPT-11 and SN-38) levels were measured in mice treated with nal-IRI in combination with gemcitabine or nab-P. Anti-tumor activity and tolerability of nal-IRI, 5-FU, gemcitabine and nab-P monotherapies and combinations were evaluated using pancreatic cancer cell line (ASPC-1 and CFPAC-1)-derived xenograft models, as well as a panel of five patient-derived xenograft models. Results: Administration of gemcitabine or nab-P prior to or simultaneously with nal-IRI resulted in unchanged or increased nal-IRI deposition, as measured by tumor CPT-11 and SN-38 levels at 24 hours post-injection. Moreover, in both cell line-derived and patient-derived xenograft models of PDAC, nal-IRI monotherapy demonstrated comparable or improved anti-tumor activity relative to gemcitabine or nab-P monotherapies. Further, nal-IRI consistently improved tumor growth inhibition and survival when used in combination with either 5-FU, gemcitabine and/or nab-P, relative to the combination of gemcitabine plus nab-P. All treatments were well-tolerated in these preclinical models. Conclusions: These findings illustrate the compatibility and therapeutic potential of nal-IRI as a foundation of first-line PDAC combination regimens, and warrant clinical evaluation.
Metabolomics analysis identifies different metabotypes of asthma severity
Authors: Stacey N. Reinke, Héctor Gallart-Ayala, Cristina Gómez, Antonio Checa, Alexander Fauland, Shama Naz, Muhammad Anas Kamleh, Ratko Djukanović, Timothy S.C. Hinks, Craig E. Wheelock
Journal: European Respiratory Journal (2017)

In this study, we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity. We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild, 20 moderate, 22 severe) using liquid chromatography–high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids, sphingolipids and free fatty acids. We conclusively identified 66 metabolites; 15 were significantly altered with asthma (p≤0.05). Levels of dehydroepiandrosterone sulfate, cortisone, cortisol, prolylhydroxyproline, pipecolate and N-palmitoyltaurine correlated significantly (p&lt;0.05) with inhaled corticosteroid dose, and were further shifted in individuals treated with oral corticosteroids. Oleoylethanolamide increased with asthma severity independently of steroid treatment (p&lt;0.001). Multivariate analysis revealed two patterns: 1) a mean difference between controls and patients with mild asthma (p=0.025), and 2) a mean difference between patients with severe asthma and all other groups (p=1.7×10 −4 ). Metabolic shifts in mild asthma, relative to controls, were associated with exogenous metabolites ( e.g. dietary lipids), while those in moderate and severe asthma ( e.g. oleoylethanolamide, sphingosine-1-phosphate, N-palmitoyltaurine) were postulated to be involved in activating the transient receptor potential vanilloid type 1 (TRPV1) receptor, driving TRPV1-dependent pathogenesis in asthma. Our findings suggest that asthma is characterised by a modest systemic metabolic shift in a disease severity-dependent manner, and that steroid treatment significantly affects metabolism.
Estrogen receptor alpha (<i>ESR1</i>) gene amplification status and clinical outcome in tamoxifen-treated postmenopausal patients with endocrine-responsive early breast cancer: An analysis of the prospective ABCSG-6 trial.
Authors: Christian F. Singer, Frederik Holst, Stefan Steurer, E C Burandt, Hellmut Samonigg, Raimund Jakesz, Herbert Stoeger, Richard Greil, Guido Sauter, Martin Filipits, Ronald Simon, Michael Gnant
Journal: Journal of Clinical Oncology (2012)

10501 Background: Estrogen receptor alpha (ERα) expression is a prognostic parameter in breast cancer and predicts response to endocrine therapy. One of the factors important for protein expression is amplification of its encoding gene ESR1. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. Methods: 394 patients who had been randomized into the tamoxifen-only arm of the prospectively designed endocrine ABCSG-06 trial and in whom FFPE tumor tissue was available were included in this analysis. Immunohistochemical ERα expression was evaluated both locally and centrally using the Allred score, while ESR1 gene amplification status was evaluated by FISH analysis using the ESR1/CEN6 ratio. Results: ESR1 copy number gains were detected in 187 of 394 (47%) tumor specimen and was associated with favorable clinical outcome. At a median follow-up of 10 years, women with intratumoral ESR1 copy number gains had a significantly longer distant recurrence-free survival (adjusted HR for relapse 0.48; 95% CI 0.28-0.83; p=0.009) and breast cancer-specific survival (adjusted HR for death 0.46; CI 0.46-0.71; p=0.006) when compared to women with normal ESR1 copy numbers. Immunohistochemical ERα protein expression, evaluated by Allred score, was significantly correlated with ESR1 copy number alterations (p&lt;0.0001; Chi-Square test), but did itself not allow to discriminate between patients with poor and good prognosis. Conclusions: ESR1 amplification status is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received 5 years of tamoxifen.
A phase II study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study (GOG-0231D).
Authors: David Michael Hyman, Michael Sill, Jonathan K Cho, Heather A. Lankes, Richard Piekarz, Martee Leigh Hensley
Journal: Journal of Clinical Oncology (2015)

e16512 Background: uLMS is an aggressive disease with limited therapeutic options. Genome wide transcriptional profiling of uterine leiomyosarcoma (uLMS) has identified frequent overexpression of gene products involved in the mitotic spindle apparatus including Aurora A Kinase. Alisertib is a highly selective small molecule inhibitor of the Aurora A kinase and has activity against uLMS in preclinical models. We conducted GOG-0231D (NCT01637961) to evaluate the activity of alisertib in uLMS. Methods: Eligibility criteria included histologically confirmed, recurrent or persistent uLMS, age ≥ 18, 1-2 prior cytotoxic regimens, and RECIST measurable disease. The primary objective of the study was to evaluate the efficacy of alisertib through the frequency of patients with objective tumor responses and the frequency who survived event-free for at least 6 months (EFS6). The endpoints for EFS were RECIST progression, death, or beginning a subsequent therapy. The null hypothesis jointly specified the probability of a patient experiencing a tumor response to less than or equal to 5% and the probability of a patient surviving event-free for at least 6 months to less than or equal to 20%. A two-stage design was used with a target accrual of 23 patients for stage 1 and 47 pts cumulative for stage 2. Confidence intervals do not correct for multiplicity. Results: 23 patients were enrolled. 2 patients were excluded on central histologic review, yielding 21 eligible patients. Median age was 61. Prior treatment was either 1 cytotoxic regimen (71.4%) or 2 (28.6%). The most common treatment related AEs (grade 3 or worse) were anemia (4), leukopenia (5), neutropenia (7), thrombocytopenia (1), mucositis (4), diarrhea (1), and palmer-planter syndrome (2). There were no objective responses (0%; 90% CI 0 ~ 10.4%). Best response was stable disease (38.1%); 12 patients had progressive disease (57.1%). EFS6 was 0% (90% CI 0 ~ 10.4%). Median PFS and OS were 1.7 (90% CI 1.4 ~ 3.2) and 14.5 months (90% CI 7.6 ~ NA), respectively. Conclusions: Alisertib did not demonstrate clinically meaningful activity in previously treated uLMS. Clinical trial information: NCT01637961.
Pilot study of intratumoral G100, toll-like receptor-4 (TLR4) agonist, therapy in patients with Merkel cell carcinoma (MCC).
Authors: Shailender Bhatia, Dafina Ibrani, Natalie Vandeven, Natalie Miller, Michi Shinohara, David Byrd, Upendra Parvathaneni, Erica Shantha, Olga K. Afanasiev, Michael Donahue, David M Koelle, Frank James Hsu, Paul Nghiem
Journal: Journal of Clinical Oncology (2015)

3083 Background: MCC is an aggressive skin cancer with suboptimal therapeutic options. Despite persistent expression of Merkel cell polyomavirus (MCPyV) proteins in ~80% of cases, these tumors are able to evade host immunity. G100 consists of a specific formulation of glucopyranosyl lipid-A (GLA), a TLR4 agonist, and is capable of directly activating dendritic cells (DCs), T cells and other effector cells and stimulating anti-tumor responses in preclinical models. Intratumoral (IT) G100 may overcome immune suppression mechanisms prevalent in MCC tumors and lead to effective local and systemic anti-tumor responses. Methods: 10 MCC patients (pts) with accessible tumor will be enrolled for G100 treatment. Pts with loco-regional MCC (Cohort A) receive 1 cycle of G100 (5 mcg/day) IT on days 1, 8 followed by definitive surgery and/or radiation (RT) starting in week 4. Pts with metastatic disease (Cohort B) receive G100 (5 mcg/day) IT on days 1, 8 and 22 of a 6-week treatment cycle. For cycles 2-4, pts receive palliative RT to the injectable tumor on day 0 followed by G100 IT weekly for 6 doses. All pts have pre- and post-treatment tumor biopsies and blood samples collected for immune monitoring. Results: 8 pts have been enrolled to date (2 cohort A; 6 cohort B); all 8 pts have completed one or more cycles of G100. Treatment-related AEs have all been grade 1 (inflammation, pain and bruising at the injection site) or transient grade 2 (inflammation). 2/2 Cohort A pts with stage IIIB MCC are recurrence-free at 11+ and 4+ months; the first of whom had a pathologic CR after two G100 IT injections. Of 6 pts with stage IV MCC in Cohort B, 2 pts have SD after cycle 1 (one with 28% regression) and 4 pts had PD. MCPyV-specific CD8 and CD4 T cells have been isolated from tumors and peripheral blood, and correlative immune studies of frequency and functional status are in progress. Conclusions: In this pilot study in MCC pts, G100 has demonstrated acceptable safety and encouraging preliminary clinical efficacy. RT was recently added to cohort B and may further enhance immune and clinical responses by increasing the release of endogenous tumor antigens. G100 IT studies in other cancers and in combination with anti-PD-1 therapy are planned. Clinical trial information: NCT02035657.
Sunitinib in Chinese patients with advanced gastrointestinal stromal tumor (GIST).
Authors: Lin Shen, Shukui Qin, Yan Sun, Jianming Xu, Carlos Linn, Qiao Wang, Liqiang Yang
Journal: Journal of Clinical Oncology (2015)

e15208 Background: The effectiveness and safety of sunitinib in GIST were largely established in Western patients. We report the first prospective study of sunitinib for this indication in China. The purpose of the single-arm study reported here was to assess use of sunitinib in Chinese patients with imatinib (IM)-resistant/-intolerant GIST. Methods: Patients failed to first line with IM at multiple centers in China received oral sunitinib 50 mg/day on the approved 4-weeks-on-2-weeks-off schedule. The primary endpoint was progression-free survival (PFS). Tumor measurements were performed every 6 weeks for the first 24 weeks and every 12 weeks thereafter by investigators using Response Evaluation Criteria in Solid Tumors, version 1.0. Secondary endpoints included overall survival (OS) and safety, which was assessed regularly. Results: A total of 60 patients were enrolled between November 2008 and December 2009 of whom 59 patients received treatment and were included in the efficacy and safety analyses. Median age (range) was 55 years (29–82) and 65% were male. Median PFS (95% CI) was 46.4 weeks (33.6–53.1). At the time of data cutoff, 50 of 59 patients (85%) had died. Median OS (95% CI) was 111.3 weeks (75.4–167.1). Most patients (98%) experienced adverse events (AEs) and 11 patients (19%) discontinued treatment due to all-causality AEs. The most common any-grade treatment-emergent AEs were leukopenia (64%), hand-foot syndrome (51%), neutropenia (49%), and fatigue (47%). The most common grade ≥ 3 treatment-emergent AEs were neutropenia (19%), decreased platelet count (17%), decreased neutrophil count (15%), and leukopenia (14%). No treatment-related deaths were reported. Conclusions: With median PFS and OS values of 46.4 weeks (10.7 months) and 111.3 weeks (25.6 months) respectively, the result in this study is comparable with that in the phase III study (Clin Cancer Res 2012;18:3170–9),even better. The safety profile was acceptable and as expected in Chinese patients. Clinical trial information: NCT00793871.