tbuckley/cabot-search huggingface dataset:
Overcoming Immune Dysregulation with Immunoengineered Nanobiomaterials
Authors: Evan A. Scott, Nicholas B. Karabin, Punn Augsornworawat
Journal: Annual Review of Biomedical Engineering (2017)

The immune system is governed by an immensely complex network of cells and both intracellular and extracellular molecular factors. It must respond to an ever-growing number of biochemical and biophysical inputs by eliciting appropriate and specific responses in order to maintain homeostasis. But as with any complex system, a plethora of false positives and false negatives can occur to generate dysregulated responses. Dysregulated immune responses are essential components of diverse inflammation-driven pathologies, including cancer, heart disease, and autoimmune disorders. Nanoscale biomaterials (i.e., nanobiomaterials) have emerged as highly customizable platforms that can be engineered to interact with and direct immune responses, holding potential for the design of novel and targeted approaches to redirect or inhibit inflammation. Here, we present recent developments of nanobiomaterials that were rationally designed to target and modulate inflammatory cells and biochemical pathways for the treatment of immune dysregulation.
Differential Expression of miRNAs in Nontumor Liver Tissue of Patients With Hepatocellular Cancer Caused by Nonalcoholic Steatohepatitis Cirrhosis
Authors: Tiebing Liang, Naga P. Chalasani, Kent Edward Williams, Vishal Sarasani, Sarath Chandra Janga, Raj Vuppalanchi
Journal: Clinical Gastroenterology and Hepatology (2016)
High-Risk Myelodysplastic Syndrome (MDS): First Results of International Phase 2 Study with Oral Farnesyltransferase Inhibitor R115777 (ZARNESTRATM).
Authors: Razelle Kurzrock, Pierre Fenaux, Azra Raza, Ghulam Mufti, Carlo Aul, Ulrich Germing, Rene Kerstens, Peter DePorre
Journal: Blood (2004)
In vivo efficacy of the CD40 agonist antibody CP-870,893 against a broad range of tumor types: Impact of tumor CD40 expression, dendritic cells, and chemotherapy
Authors: R. P. Gladue, S. H. Cole, C. Donovan, T. Paradis, R. Alpert, E. Natoli, V. Bedian
Journal: Journal of Clinical Oncology (2006)

2514 Background: CP-870,893 is a fully human IgG 2 CD40 agonist antibody currently in early clinical trials. In vitro studies demonstrate its ability to bind human CD40 and enhance dendritic cell costimulatory molecule expression and cytokine production. Methods: In order to assess its potential for cancer therapy, we evaluated the anti-tumor efficacy of CP-870,893 against several CD40 pos and CD40 neg human tumors in SCID beige mice. We specifically addressed the role of tumor CD40 expression, the impact of re-population with human dendritic and T cells on efficacy, and it’s potential to act in synergy with chemotherapeutic agents. Results: We demonstrate that a single i.p. injection of CP-870,893 (T 1/2 ∼ 7 days) prevented the growth of several subcutaneous CD40 pos tumors including two B cell lymphomas, the breast carcinoma BT-474, and the prostate tumor PC-3 (ED 50 = 0.02 mg/kg; C eff ∼100 ng/mL). Efficacy was demonstrated when CP-870,893 was administered at the time of tumor challenge, but was also observed when treatment was delayed until tumors were well established. Although efficacious against CD40 pos tumors, CP-870,893 had no effect on the growth of CD40 neg/low tumors unless mice were repopulated at the tumor site with both naïve human dendritic cells and T cells. In these repopulated animals, i.p. administration of CP-870,893 inhibited the growth of a CD40 low colon carcinoma and a CD40 neg erythroleukemic tumor (ED 50 = 0.005 mg/kg). The presence of human T cells and dendritic cells at the tumor site also improved the activity of CP-870,893 against CD40 pos tumors, reducing the ED 50 and C eff &gt;10-fold as compared to its effects in the absence of these cells, suggesting a synergy between direct CD40 mediated tumor killing and immune activation. Further, when administered as part of a combination treatment with a sub-optimal dose of cisplatin, improved activity was observed which resulted in tumor regression. Conclusions: These studies demonstrate the potent, broad-spectrum anti-tumor activity of CP-870,893 through both direct and immune mediated effects, its increased efficacy when co-administered with chemotherapeutic agents, and suggest its potential utility as a therapy for human cancer. [Table: see text]
Effect of high-dose vitamin D on joint pain and fatigue from adjuvant letrozole
Authors: Q. J. Khan, P. S. Reddy, B. F. Kimler, P. Sharma, S. Baxa, A. P. O’dea, C. J. Fabian
Journal: Journal of Clinical Oncology (2008)

9618 Background: Vitamin D (vitD) deficiency is associated with non-specific joint pain and chronic fatigue, and these symptoms are common in women with breast cancer on aromatase inhibitors (AIs). We conducted a prospective study to determine the effect of high dose vitD on joint pain and fatigue in women on adjuvant letrozole. Methods: Postmenopausal women with invasive breast cancer who were candidates for an adjuvant AI. Serum 25 OHD (LC/MS/MS; Quest) was measured at baseline, wk 10 and wk 16 (end of study). At baseline all women started 2.5 mg/d of letrozole and standard dose calcium (1,200 mg/d) + vitD (600 IU/d). At wk 4 women with serum 25 OHD ≤ 40 ng/ml received 50,000 IU of oral vitD3/wk for 12 wks. BFI (fatigue assessment), HAQ II (assessment of disability from joint symptoms), and assessment of severity of joint symptoms were conducted at baseline, wk 4 and wk 16. Results: 60 women participated. At baseline, 63% were vitD insufficient (<32 ng/ml). 49 of 50 women who received high dose vitD had serum 25 OHD levels >32 ng/ml by wk 10. Nine had vitD > 40 ng/ml at baseline and did not get high dose vitD. Despite standard dose Ca + D with initiation of letrozole, serum 25OHD levels dropped in 7 of 9 women (median levels: 46 and 40 ng/ml at wks 0 and 16). Joint pain was more likely to worsen during first 4 wks (letrozole + standard vitD); in contrast, more women had improvement in joint pain during next 12 wks (high dose vitD) (see Table). Similar trend was observed for fatigue. For HAQII, equal number of women improved (37%) vs worsened (32%) in first 4 wks; during next 12 wks, twice as many improved (44%) as worsened (22%); however, results of HAQII were not statistically significant. Conclusions: In breast cancer patients on letrozole, high dose VitD effectively increases serum 25OHD levels and appears to provide clinical relief from symptoms of fatigue, joint pain, and disability from joint pain. With standard dose vitD, serum 25OHD levels do not improve and may even decrease in women on letrozole. Table: Effect of vitamin D on AI associated arthralgias and fatigue Joint Pain Fatigue (BFI) Week 0–4 * Week 4–16 ** Week 0–4 * Week 4–16 ** Improved (% women) 7 23 40 56 Worsened (% women) 37 32 53 36 No change (% women 56 45 7 8 P value .002 .09 .07 .038 * Letrozole initiated at week 0; During 0–4 weeks women on letrozole before high dose vit D; ** High dose vit D 50,000 IU initiated at week 4 and continued for 12 weeks. No significant financial relationships to disclose.
Estimating the Relative Effectiveness of Treatments in Relapsed/Refractory Multiple Myeloma through a Systematic Review and Network Meta-Analysis
Authors: Kai Ruggeri, Áine Maguire, Susanne Schmitz, Elisa Haller, Cathal Walsh, Jack Bowden, Isla Kuhn, Ayesha Khan, Gordon Cook, Michael O'Dwyer
Journal: Blood (2015)
Clinical and Biologic Activity of the Heat Shock Protein-90 (HSP-90) Inhibitor 17-AAG in Patients with Relapsed Lymphoma.
Authors: Anas Younes, Amanda R Copeland, Jorge Romaguera, Luis Fayad, Michelle Fanale, Silvana de Castro Faria, L. Jeffrey Medeiros, S. Percy Ivy
Journal: Blood (2009)
Response to Comment on Qian et al. Metabolic Effects of Monounsaturated Fatty Acid–Enriched Diets Compared With Carbohydrate or Polyunsaturated Fatty Acid–Enriched Diets in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care 2016;39:1448–1457
Authors: Frank Qian, Frank B. Hu
Journal: Diabetes Care (2016)

We thank Schwingshackl and Hoffmann (1) for their insights and for putting our article into the broader context of other scientific literature. As the authors mentioned, our study sought to address a knowledge gap noted in a prior position statement regarding whether monounsaturated fatty acids (MUFA) are an important constituent of optimal nutrition therapy for patients with type 2 diabetes (2,3). Prior to our report, most …
Disturbed Blood Flow Induces RelA Expression via c-Jun N-Terminal Kinase 1
Authors: Simon Cuhlmann, Kim Van der Heiden, David Saliba, Jordi L. Tremoleda, Magdy Khalil, Mustafa Zakkar, Hera Chaudhury, Le Anh Luong, Justin C. Mason, Irina Udalova, William Gsell, Hazel Jones, Dorian O. Haskard, Rob Krams, Paul C. Evans
Journal: Circulation Research (2011)

Rationale: The nuclear factor (NF)-κB pathway is involved in arterial inflammation. Although the signaling pathways that regulate transcriptional activation of NF-κB are defined, the mechanisms that regulate the expression levels of NF-κB transcription factors are uncertain. Objective: We studied the signaling mechanisms that regulate RelA NF-κB subunit expression in endothelial cells (ECs) and their role in arterial inflammation. Methods and Results: Gene silencing and chromatin immunoprecipitation revealed that RelA expression was positively regulated by c-Jun N-terminal kinase (JNK) and the downstream transcription factor ATF2 in ECs. We concluded that this pathway promotes focal arterial inflammation as genetic deletion of JNK1 reduced NF-κB expression and macrophage accumulation at an atherosusceptible site. We hypothesized that JNK signaling to NF-κB may be controlled by mechanical forces because atherosusceptibility is associated with exposure to disturbed blood flow. This was assessed by positron emission tomography imaging of carotid arteries modified with a constrictive cuff, a method that was developed to study the effects of disturbed flow on vascular physiology in vivo. This approach coupled to en face staining revealed that disturbed flow elevates NF-κB expression and inflammation in murine carotid arteries via JNK1. Conclusions: We demonstrate that disturbed blood flow promotes arterial inflammation by inducing NF-κB expression in endothelial cells via JNK-ATF2 signaling. Thus, our findings illuminate a novel form of JNK–NF-κB crosstalk that may determine the focal nature of arterial inflammation and atherosclerosis.
Clinicohistologic Assessment of Bone Marrow Engraftment In Patients with Hematologic Malignancies Received Double Umbilical Cord Blood Transplantation – A Single Institutional Observation
Authors: Deniz Peker, Marcie Tomblyn, Taiga Nishihori, Elizabeth M. Sagatys, Kaaron Benson, Xiaohui Zhang, Lynn Moscinski, Ling Zhang
Journal: Blood (2011)
A double-blind, randomized, placebo-controlled study of fentanyl buccal tablet (FBT) in opioid-tolerant patients with chronic cancer pain and breakthrough pain
Authors: N. Slatkin, F. Xie, T. Segal, J. Messina
Journal: Journal of Clinical Oncology (2007)

9057 Background: Episodes of cancer-related breakthrough pain (BTP) often peak in intensity in minutes. Pain relief with traditional, short-acting oral opioids is often not achieved for =30 min. Fentanyl buccal tablet (FBT) has a rapid onset of analgesia. This double- blind, randomized, placebo-controlled study evaluated the efficacy and safety of FBT in opioid-tolerant patients with cancer and BTP. Methods: After open-label titration to establish a successful dose of FBT, patients were randomized to prespecified, double-blinded sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) was assessed from 5 to 120 min post dose. The primary efficacy measure was the sum of PI differences (PIDs) for the first 60 min (SPID 60 ); secondary measures included PIDs, =33% and =50% improvements in PI, and global medication performance (GMP). Use of supplemental BTP medication and adverse events (AEs) were reported. Results: 129 patients were enrolled; 87/125 treated (70%) identified an effective FBT dose and entered the double-blind phase. SPID 60 significantly favored FBT vs placebo (mean±SEM, 9.7±0.63 vs 4.9±0.50; p&lt;0.0001). PID differed significantly vs placebo at 10 min (mean±SEM, 0.9±0.09 vs 0.5±0.09; p&lt;0.0001) and at all time points through 2 hr (p&lt;0.0001). Improvements in PI of =33% and =50% from baseline occurred in a larger proportion of episodes following FBT vs placebo from 10 min (16% vs 10% and 7% vs 4%, respectively; p&lt;0.05) through 2 hr (74% vs 38% and 66% vs 28%; p&lt;0.0001). Ratings of GMP were superior for FBT vs placebo at 60 and 120 min (p&lt;0.0001). Supplemental opioids were required for approximately 3 times more BTP episodes following placebo compared with FBT. AEs were typical for opioids, e.g. nausea (13%), dizziness (11%), fatigue (8%), and constipation (6%). Application site-related AEs occurred in 12 patients (10%). A total of 11/125 (9%) patients had =1 serious AE; these were considered not/unlikely to be related to study drug. Conclusions: FBT was effective and well tolerated in the management of BTP in opioid-tolerant patients with cancer-related pain, with an early onset of analgesia and a sustained duration of effect. No significant financial relationships to disclose.
Prevalence and Clinico-Pathological Attributes of c-MYC Rearranged High-Grade B-Cell Non Hodgkin Lymphomas (NHL): Single Centre Experience
Authors: Manju Sengar, Sridhar Epari, Hasmukh Jain, Tanuja Shet, Sumeet Gujral, Hari Menon, Uma Dangi
Journal: Blood (2015)
Global Phosphoproteomic Analysis of B-Cell Lymphoma Signatures Reveals the Role of Active B-Cell Receptor Signaling in Germinal Center Derived NHLs
Authors: Delphine C.M. Rolland, Venkatesha Basrur, Kevin Conlon, Thomas Wolfe, Damian Fermin, Megan S Lim, Kojo S.J. Elenitoba-Johnson
Journal: Blood (2011)
Immunohistochemical study of excision repair cross-complementation-1 (ERCC1) in neuroendocrine lung tumors
Authors: M. A. Sikder, R. Simon, H. Xu, K. J. Pandya, P. A. Bourne, H. L. Wang
Journal: Journal of Clinical Oncology (2008)

22085 Background: Excision repair cross-complementation 1 (ERCC1) is reported to be variably expressed in non-small-cell lung carcinomas (NSCLC), and to be a predictor of response to platinum-based chemotherapy and patient survival (Olaussen KA, et al. NEJM 2006). Information on ERCC1 expression in pulmonary neuroendocrine tumors, however, is sparse. Methods: Using a monoclonal antibody against ERCC1 (Lab Vision, Fremont, Calif.), we used immunohistochemical analysis to evaluate 48 surgically-resected pulmonary tumors: 20 16 small cell lung carcinomas (SCLC), 12 large cell neuroendocrine carcinomas (LCNEC), 6 atypical carcinoids (AC), and 14 typical carcinoids (TC). Nuclear uptake of the antibody was considered positive. The percentage of positively stained tumor cells was recorded and the staining intensity was graded as weak, moderate or strong. Lymphocytes and bronchiolar epithelium served as internal controls, which were used as references for grading the staining intensity. Results: Overall, 44 of 48 (92%) neuroendocrine tumors stained positive for ERCC1. Strong and diffuse nuclear staining was detected in 14 (87.5%) SCLC, 4 (66.7%) AC, and 10 (71.4%) TC. In contrast, strong and diffuse nuclear staining was seen in only 3 (25%) LCNEC, although a majority of them stained weakly and/or focally. More detailed results are summarized in the Table. Conclusions: All types of neuroendocrine lung tumors expressed ERCC1 with high frequencies. With the exception of LCNEC, the other types did so in a strong and diffuse pattern. Our observations are at variance with recently published data (Lee HW, et al. Lung Cancer 2008), which may be due to small sample size, and/or inherent biological differences between the two study populations. This study warrants further investigation in the role of ERCC1 protein. Tumor type Negative Focal and/or Weak Strong and/or Diffuse SCLC (n = 16) 0 2 (12.5%) 14 (87.5%) LCNEC (n = 12) 1 (8.3%) 8 (66.7%) 3 (25%) AC (n = 6) 1 (16.7%) 1 (16.7%) 4 (66.7%) TC (n = 14) 2 (14.3%) 2 (14.3%) 10 (71.4%) No significant financial relationships to disclose.
Interim results of phase II trial of pegylated liposomal doxorubicin (PLD) followed by bexarotene in advanced cutaneous T-cell lymphoma (CTCL).
Authors: D. J. Straus, M. Duvic, S. M. Horwitz, K. B. Hymes, A. Goy, F. J. Hernandez-Ilizaliturri, T. Feldman, B. Wegner, P. Myskowski
Journal: Journal of Clinical Oncology (2010)

8053 Background: PLD is approved for treatment of Kaposi's sarcoma and concentrates highly in the skin. Overall response (ORR: complete+partial response rates) ranging from 61% to 88% and CRs 22 to 44% have been reported with PLD in CTCL patients (pts) without strict response criteria. Bexarotene (Bex) is a synthetic retinoid with an ORR of approximately 50% in relapsed/refractory CTCL. To clarify the true ORR for PLD and to assess whether the ORR and remission durations can be improved by sequential Bex following PLD, a multi-institutional phase II trial was undertaken for pts with advanced/refractory CTCL. Methods: Pts were treated with PLD 20 mg/m2 IV every 2 weeks for 8 doses (16 weeks) followed by 16 weeks with Bex 300 mg/m2 orally. Lymph node and skin assessments were performed after 8 and 16 weeks. The Severity-Weighted Assessment Tool (SWAT) was the primary measure of skin response with the Composite Assessment of Index Lesion Severity and a self-reported pruritus scale as secondary measures. Results: Twenty-seven of planned 37 pts with stage IV (14) or refractory earlier stage (13) CTCL have been enrolled. Median follow-up is 5 mo. (2.1-22.1 mo.) For 22 assessable pts: ORR 8/22 (36%: PR 7, clinical CR 1). Median progression free survival (PFS) is 6 mo. Seven pts died of disease progression. Treatment related grade 3/4 adverse events occurred in 8 pts (6 pts: tumor pain, neutropenia or infection; 2 pts: grade 3 hand-foot syndrome). Conclusions: With strict criteria, so far PLD ORR is high but lower than that previously reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Ortho Biotech
Sequential angiogenic blockade for the treatment of recurrent ovarian cancer.
Authors: U. Matulonis, L. Pereira, H. Lee, S. M. Campos, J. Liu, J. Lee, C. Whalen, T. Atkinson, M. Hill, S. T. Berlin
Journal: Journal of Clinical Oncology (2010)

5083 Background: Ovarian cancer (ov ca) growth is driven by angiogenesis; drugs that block angiogenesis can result in anti-ov ca activity. This study sought to sequentially block angiogenesis by adding stepwise antiangiogenic agents targeting different aspects of the angiogenic cascade. Methods: Objectives were to assess the safety of sequential bevacizumab (bev) and oral low dose cyclophosphamide (Cy) and assess proportion of patients who remain on study at 3 months; others were toxicity, RR, and PFS. Eligibility: recurrent ov, tubal, or peritoneal ca, max of 2 lines of therapy for recurrent ca (biologic therapies included), platinum resistant or sensitive recurrence, ECOG PS of 0 or 1, measurable cancer by RECIST or CA125, no preexisting significant hypertension, and no evidence of SBO or impending SBO. Pts started on bev 15 mg/kg IV q21 days and were assessed radiographically every 2 cycles. If CR, PR, or SD and no significant toxicities occurred, patients continued on bev. If pts had PD and were clinically stable, Cy 50 mg PO daily was added to bev. Results: 20 patients were enrolled which was the target enrollment. 13 pts had ov, 2 had tubal, and 5 had peritoneal cancer. 14 pts had plat resistant cancer, and 6 had plat-sensitive. 7 pts had 2 prior lines for recurrence, 9 had 1 prior line, and 4 had no prior lines for recurrence. Grade 3 and 4 toxicities included 7 pts with grade 3 HTN, 1 pt with GIP, and 1 pt with acute MI. Of the 20 pts, 16 pts remained on study for at least 3 months or 4 cycles (80%). 2 pts had a PR, 16 pts had SD as their best response with bev, 1 pt is too early to evaluate, 1 pt had PD as their best response on bev and is now on PO Cy. 2 pts were removed during bev for toxicities (GIP after cycle 2 and MI following cycle 4), and 10 pts remain on single agent bev without progression. Cy has been started in 8 patients; of those 8, 4 pts attained SD, 3 pts had PD, and 1 pt is too early for evaluation. Conclusions: Bev as a single agent demonstrates biologic activity in recurrent ovarian cancer. Preliminary data suggests that the addition of PO Cy to bev following tumor progression on bev appears tolerable and can lead to stable disease. This observation may have implications in the design of future clinical trials using antiangiogenic agents for recurrent ovarian cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Abstract #4982: The mesenchyme-specific gene HMGA2 modulates tumor progression and metastasis
Authors: Asahiro Morishita, M. Raza Zaidi, Akira Mitoro, Devipriya Sankarasharma, Matthias Szabolcs, Yasunori Okada, Jeanine D'Armiento, Kiran Chada
Journal: Cancer Research (2009)

HMGA2, a gene that is predominantly expressed in the undifferentiated mesenchyme, is expressed in multiple epithelial tumor cell types and epithelial cells that are transformed. In order to determine the relationship between HMGA2 and EMT, we examined the HMGA2 expression in two invasive (MDA-MB-231 and MDA-MB-435) and three non- or poorly invasive (T47D, BT474, and MCF-7) human breast cancer cell lines. Only the invasive but not the noninvasive cell lines express HMGA2. The epithelial-mesenchymal transition (EMT) is implicated in the advancement of a carcinoma to a metastatic phenotype and the HMGA2 expressing breast cancer cell lines were found to express a number of molecular characteristics indicative of cells undergoing the EMT including the EMT-specific markers such as expression of vimentin, loss of E-cadherin expression and the relocalization of beta-catenin. To directly test if HMGA2 was sufficient for the EMT in epithelial cells, stable clones derived from SW480 colorectal cancer and MCF-7 breast cancer epithelial cell lines were established that ectopically expressed HMGA2 under the control of the CMV promoter. Both transfected cells revealed a pronounced elongated, spindle-shaped mesenchymal phenotype and exhibited EMT-specific markers. Expression of phosphorylated smad3 was increased in the HMGA2-transfected cells compared to vector-transfected cells as is consistent with its function in EMT. The critical role of HMGA2 in tumor progression was confirmed when HMGA2 loss-of-function experiments demonstrated an 80% reduction in tumor multiplicity in a mouse model of breast cancer. The relevance of these studies to human cancer was revealed when the HMGA2-positive cells were identified at the invasive front and correlated with EMT in human colorectal adenocarcinomas. These studies strongly suggest that the mesenchyme-specific gene, HMGA2, could play a critical role in EMT and progression to metastasis of human epithelial cancers.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4982.
Ganglion Cyst on 131I Whole-Body Scintigraphy
Authors: Anunita Khasgiwala, Kent P. Friedman, Munir Ghesani, Roy A. Raad
Journal: Clinical Nuclear Medicine (2016)

Interpretation of iodine I whole-body scintigraphy can be challenging, as there are many nonpathologic findings that may present with increased radiotracer uptake. Radiotracer uptake has been reported in the literature involving the salivary glands, thymus, renal cysts, skin contamination, and other benign etiologies. We present the case of an incidental right wrist ganglion cyst demonstrating persistent increased uptake on I whole-body scintigraphy.
GW26-e1244 Effects of Lipopolysaccharide on the Growth and Proliferation of Human Coronary Artery Smooth Muscle Cells in Vitro
Authors: Hongmei Li, Mengqiong Sun, Ang Gao, Zhen Wang, Xueqing Yang, Tian Sun, Chang-bo Xuan, Xian Wang
Journal: Journal of the American College of Cardiology (2015)