tbuckley/cabot-search huggingface dataset:
Development of a tissue-equivalent human liver phantom for <sup>90</sup>Y-microsphere dosimetry studies and testing of other local ablation therapies.
Authors: Andrew S. Kennedy, Patrick McNeillie, William Dezarn
Journal: Journal of Clinical Oncology (2012)

244 Background: 90 Y-microsphere brachytherapy for unresectable hepatic cancers is an increasingly popular therapy. The beta radiation dosimetry involved is not well understood and there is lack of pre and post treatment planning capabilities. Methods: A phantom was developed with tissue equivalent electron density, accurate anthropomorphic size, shape and volume to an adult human liver, with similar properties in response to heat, cold, radiation and diagnostic imaging as human liver tissue. Space-occupying masses were created to accommodate implantation of microspheres to simulate a human treatment. Imaging included MRI, CT and SPECT gamma scans pre and post implantation of 90 Y-microspheres. Results: A phantom was produced that was shaped from a mold of an adult human liver. A mass with a different density than the liver was created in the right lobe that had a 3mm – 6mm rim for microsphere implantation. A known quantity of 99mTc was implanted into the left lobe. 90 Y-microspheres of known activity were implanted in the periphery of the right lobe tumor. CT contrast was mixed with the microspheres to improve localization on subsequent CT scans. The electron density of the phantom was identical to human liver. Microsphere implantation was limited to the outer 6 mm of the right lobe tumor and 99mTc limited to the left lobe. Spatial resolution in 3D was excellent on all three modalities (MRI, CT and SPECT gamma). Conclusions: A human liver phantom as described will be a useful tool in future studies of beta radiation dosimetry, cross sectional and nuclear imaging and tissue responses. The next generation phantom is being developed with blood vessel-like branching channels to allow fluids to pass into and through the phantom similar in scale and diameter to hepatic vessels and tumors.
Oral Dabigatran Etexilate Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Hip or Knee Arthroplasty: A Pooled Analysis of Four Randomized Trials
Authors: Michael H Huo, Andreas A Kurth, Ola E Dahl, Andreas Clemens, Stefan Hantel, Martin Feuring, Richard J Friedman, Bengt I Eriksson
Journal: Blood (2011)
Newly Diagnosed Multiple Myeloma Is Associated with Enhanced TF Pathway Activation, Thrombin Generation and Increased Concentration of Procoagulant Microparticles
Authors: Grigorios T. Gerotziafas, Flora Zagouri, Despina Fotiou, Theodoros N. Sergentanis, Kimon Stamatelopoulos, Theodora Psaltopoulou, Efstathios Kastritis, Evangelos Terpos, Patrick Van Dreden, Aurélie Rousseau, Ilias Evmorfiadis, Ismail Elalamy, Annette Larsen, Meletios A. Dimopoulos
Journal: Blood (2015)
Geographic disparity in the use of surgical management (SM) and radiotherapy (RT) for female breast cancer (BC) in Wisconsin (WI).
Authors: A. Ho, J. R. White, J. B. Owen, A. Trentham-Dietz, J. F. Wilson
Journal: Journal of Clinical Oncology (2011)

209 Background: The WICaRE Program is a part of the cross sectional Patterns of Care Study–Breast and Prostate (PoC-BP) that sought to evaluate the patterns of BC care in the state WI and to identify areas for potential improvement in data collection and factors associated with variation in care. This study was to examine the geographic disparities in SM and the use of RT in female BC patients diagnosed in WI in 2004. Methods: The Wisconsin Cancer Reporting System (WCRS) receives reports from 130+ facilities. Information of patient (disease status, sociodemographic, treatment, county of residence) was obtained from cancer registries and supplemental data was reabstracted from medical charts across 66 counties. Geographic regions were counties grouped by WI Dept. of Health Services (DHS) as Northeastern (NE), Northern (N), Southeastern (SE), Southern (S), Western (W). Results: A total of 1037 cases were reported. 25% age 20-49, 49% age 50-69, and 28% age 70+; Caucasian had 82%, black 10% and others 8%. 34% had T1 stage, 9% T2, 4% T3+, and 53% TX-T0/unknown stage. 46% had reported mild comorbidity, 9% had moderate or severe comorbidity. Majority (73%) lived in the Metropolitan Statistical Area (MSA). 29% patients from NE region, 10% from N, 36% SE, 17% S and 8% W. Patients in the S and W had significantly lower % who received RT (46 and 48% respectively) than those in NE (61%), N (62%) and SE (63%), p=0.01; % mastectomy (MA) by regions were 43% (NE), 42% (N), 33% (SE), 47% (S) and 35% (W), p=0.009. Multivariate models adjusting for disease status, comorbidity, and sociodemographic factors showed that patients in MSA region were more likely to have RT compared to those in non-MSA (odds ratio, OR=1.66, 95%CI=1.14-2.40), but those in S were less likely than those in SE (OR=0.59, 95%CI=0.38-0.91). Patients in MSA had a decreased likelihood of undergoing mastectomy. NE (OR=1.6, 95%CI=1.08-2.29) and S (OR= 2.04, 95%CI=1.31-3.17) had significantly higher odds of having MA than those in SE. Conclusions: This study showed evidence of geographic disparity in medical care for BC patients in Wisconsin. Identifying factors mediating this disparity will help in developing appropriate treatment options and improving outcomes.
A Phase II Study of Nilotinib, a Novel Tyrosine Kinase Inhibitor Administered to Patients with Imatinib Resistant or Intolerant Chronic Myelogenous Leukemia (CML) in Chronic Phase (CP), Accelerated Phase (AP) or Blast Crisis (BC) Who Have Also Failed Dasatinib Therapy.
Authors: Francis Giles, Philipp le Coutre, Kapil Bhalla, Gianantonio Rosti, G.J. Ossenkopplele, Giuliana Alimena, Aaron Weitzman, Teresa Rafferty, Ming Zheng, Hagop Kantarjian
Journal: Blood (2006)
Changing national trends and survival in stage IV gastric cancer.
Authors: Anna M. Leung, Connie G. Chiu, Danielle M. Hari, Myung-Shin Sim, Anton J. Bilchik
Journal: Journal of Clinical Oncology (2012)

81 Background: With more effective systemic chemotherapy, the role for palliative gastrectomy in patients with Stage IV gastric cancer has been questioned. Methods: Using the National Cancer Data Base we identified 29,655 patients with Stage IV gastric cancer over a 14 year period (1994-2008). Patient demographics, tumor related features, and treatments were analyzed. Overall survival rates were examined using log-rank test power analysis. Results: There was a decrease in surgical resection from 31.2% in 2000 to 22% in 2008 (p&lt;0.0001), a decrease in radiation from 20% in 2000 to 18.5% in 2008 (p= 0.0009), and an increase in systemic therapy from 45.5% in 2000 to 55.1% in 2008 (p&lt;0.001). There were no differences in gender, age, or histology, but there was a decreasing trend of Caucasians diagnosed (p&lt;0.0001). Survival rates decreased significantly over time p&lt;0.05 (see table below). Conclusions: Over the past 14 years there has been an increase in the use of systemic chemotherapy and a reduction in palliative gastrectomy for stage IV gastric cancer. The negative impact on survival suggests that treatment pathways be re-evaluated. [Table: see text]
Effect of lenalidomide on the response of bladder cancer to BCG immunotherapy in an in vivo murine model.
Authors: Eugene K. Lee, Jinesh Gerald, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2012)

288 Background: Intravesical BCG is the gold standard for non-muscle-invasive bladder cancer (NMIBC). However, many patients do not respond to therapy while others relapse and/or progress. As a result, there remains a need for therapies that can enhance the efficacy of BCG. We explore the efficacy of lenalidomide, an immunomodulatory agent used in multiple myeloma and myelodysplastic syndrome, in combination with BCG in vitro and in an in vivo bladder cancer model. Methods: We studied the effects of lenalidomide in combination with BCG induced cytokines in MBT-2 cells using PI-FACS. For in vitro studies, we used 10 and 100 nM of lenalidomide in combination with TNF-a and FasL. We then performed Western blotting for cell cycle and apoptosis regulatory proteins. Subsequently, we tested the efficacy of this combination in an immunocompetent murine model of bladder cancer with MBT-2 cells in C3H mice using the flank injection method. Drug dosages were 30 mg/kg for lenalidomide and 10 5 CFU of BCG. Tumor growth curves were created for the control, lenalidomide, BCG and combination treatment mice groups. Immunohistochemistry (IHC) was then performed using antibodies against proteins related to cell cycle, apoptosis, angiogenesis and immune response. Results: PI-FACS identified increased DNA fragmentation in the combinations of lenalidomide and TNF-a and FasL compared to control and each agent alone. Using Western blotting, we demonstrated that the combination resulted in apoptosis via caspase-3 activation. In the murine model, combination therapy resulted in a statistically significant decreased tumor size compared to the control group. While the BCG alone and lenalidomide alone groups did show a trend toward smaller tumor, they did not reach statistical significance. Furthermore, the TUNEL assay showed a substantial increase in apoptosis only in the combination group. Immunohistochemistry demonstrated decreased angiogenesis in all treatment groups compared to control, as well as, decreased T-cell infiltration. Conclusions: Our study demonstrates a potential role for the immunomodulatory agent, lenalidomide, in combination with BCG for NMIBC. This in vivo model serves as a template for future clinical trials.
Novel Hybrid Phenotype Revealed in Small Cell Lung Cancer by a Transcription Factor Network Model That Can Explain Tumor Heterogeneity
Authors: Akshata R. Udyavar, David J. Wooten, Megan Hoeksema, Mukesh Bansal, Andrea Califano, Lourdes Estrada, Santiago Schnell, Jonathan M. Irish, Pierre P. Massion, Vito Quaranta
Journal: Cancer Research (2016)

Abstract Small cell lung cancer (SCLC) is a devastating disease due to its propensity for early invasion and refractory relapse after initial treatment response. Although these aggressive traits have been associated with phenotypic heterogeneity, our understanding of this association remains incomplete. To fill this knowledge gap, we inferred a set of 33 transcription factors (TF) associated with gene signatures of the known neuroendocrine/epithelial (NE) and non-neuroendocrine/mesenchymal-like (ML) SCLC phenotypes. The topology of this SCLC TF network was derived from prior knowledge and was simulated using Boolean modeling. These simulations predicted that the network settles into attractors, or TF expression patterns, that correlate with NE or ML phenotypes, suggesting that TF network dynamics underlie the emergence of heterogeneous SCLC phenotypes. However, several cell lines and patient tumor specimens failed to correlate with either the NE or ML attractors. By flow cytometry, single cells within these cell lines simultaneously expressed surface markers of both NE and ML differentiation, confirming the existence of a “hybrid” phenotype. Upon exposure to standard-of-care cytotoxic drugs or epigenetic modifiers, NE and ML cell populations converged toward the hybrid state, suggesting possible escape from treatment. Our findings indicate that SCLC phenotypic heterogeneity can be specified dynamically by attractor states of a master regulatory TF network. Thus, SCLC heterogeneity may be best understood as states within an epigenetic landscape. Understanding phenotypic transitions within this landscape may provide insights to clinical applications. Cancer Res; 77(5); 1063–74. ©2016 AACR.
Thrombopoietin Activates STAT2 Inducing Type I Interferon Effects and Gene Expression: Implications for in Vivo Tpo Treatment and for Myeloproliferative Neoplasms
Authors: Stefan N Constantinescu, Jean-Philippe Defour, Celine Mouton, Isabelle Plo, William Vainchenker, Jean-Luc Villeval, Thomas Michiels, Judith Staerk, Christian Pecquet
Journal: Blood (2014)
Capsaicin, a novel radiosensitizer, acts via a TRPV6 mediated phenomenon.
Authors: L. Klotz, N. Venier, A. J. Colquhoun, H. Sasaki, D. A. Loblaw, N. Fleshner, V. Venkateswaran
Journal: Journal of Clinical Oncology (2011)

23 Background: Radiosensitizing agents sensitize cells to the lethal effects of ionizing radiation (IR). This permits use of lower doses of radiation to achieve equivalent cancer control thereby minimizing adverse effects to normal tissues. Given their lack of toxicity compounds occurring naturally in the diet make ideal potential radiosensitizing agents. Capsaicin, a compound found in the Capsicum sp. of plants, is a widely consumed food additive in areas with low PCa incidence. Traditionally capsaicin is used to treat chronic pain syndromes; however, recently evidence using in vitro PCa models describes its anti-carcinogenic potential. The transient receptor potential vanilloid-receptor (TRPV)-1 and TRPV6 cation selective channels are thought to be partly responsible for mediating these effects. TRPV-1 and TRPV-6 expression is up-regulated in PCa tissue correlating directly with increasing tumor grade. This suggests TRPV1 and/or TRPV6 may be potential therapeutic targets for capsaicin mediated interventions in PCa patients. As IR and capsaicin both promote apoptosis and inhibit cell cycle progression in vitro we hypothesize an at least additive effect of combining these two therapies. Methods: Using clonogenic assays we assessed the effect of ionizing radiation (1-8 Gy) and/or capsaicin (1-10μ M) on colony formation rates in 4 human PCa cell lines (LNCaP, PC3, PC3AR2, DU145). Proliferative, apoptotic, TRPV-6 protein markers were assessed using Western blot analyses. Results: Exposure of cells to capsaicin (1-10μ M) or IR (1-8Gy) caused significant dose-dependent inhibition of colony formation (p&lt;0.001). Combining capsaicin with IR resulted in further significant inhibition of colony formation rates (P&lt;0.001). Western blot analyses showed LNCaP cells treated with capsaicin and/or IR to have increased expression of pro- apoptotic proteins BAX and Bad, tumor-suppressor proteins p21 and p27 and reduced androgen-receptor. Additionally, capsaicin monotherapy caused a dramaticalteration in TRPV1 and TRPV6 expression. Conclusions: These studies confirm the radiosensitizing capacity of capsaicin in PCa cells in vitro. Ongoing studies are further delineating the mechanism of interaction of these treatment modalities. No significant financial relationships to disclose.
Analysis of Minimal Residual Disease in Follicular Lymphoma Patients in Gadolin, a Phase III Study of Obinutuzumab Plus Bendamustine Versus Bendamustine in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Authors: Christiane Pott, David Belada, Nathalie Danesi, Günter Fingerle-Rowson, John Gribben, Chris Harbron, Eva Hoster, Brad S Kahl, Kirsten Mundt, Catherine Sebban, Laurie H Sehn, Bruce D. Cheson
Journal: Blood (2015)
ARHGAP21 Is Upregulated and Triggers the Modulation of Rho Gtpase Signaling Pathways during Megakaryocytic Differentiation
Authors: Vanessa Aline Bernusso, Mariana Lazarini, João Agostinho Machado-Neto, Karin Spat Albino Barcellos, Sara Teresinha Olalla Saad
Journal: Blood (2015)
Expression of Endomucin, a CD34-Like Sialomucin, Marks Definitive Hematopoietic Stem Cells throughout Development.
Authors: Azusa Maeda, Atsushi Iwama, Koji Eto, Hideo Ema, Toshio Kitamura, Dietmar Vestweber, Hiromitsu Nakauchi
Journal: Blood (2004)
The impact of co‐morbidity burden on appropriate implantable cardioverter defibrillator therapy and all‐cause mortality: insight from Danish nationwide clinical registers
Authors: Anne Christine Ruwald, Michael Vinther, Gunnar H. Gislason, Jens Brock Johansen, Jens Cosedis Nielsen, Helen Høgh Petersen, Sam Riahi, Christian Jons
Journal: European Journal of Heart Failure (2016)
Evaluation of complete pathologic response and histologic toxicity using a subcutaneous delivery system with combination nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer in vivo.
Authors: S. M. Cohen, R. Mukerji, S. Cai, I. Damjanov, M. L. Forrest, M. S. Cohen
Journal: Journal of Clinical Oncology (2011)

279 Background: Systemic doxorubicin (DOX) and platinum agents in breast cancer can be limited by their toxicity and have low penetration into lymphatics contributing to locoregional (LR) recurrence. Subcutaneous (s.c.) delivery of single agent nanoconjugated (HA-DOX) or cisplatin (HA-CIS) can significantly boost LR drug delivery with lower toxicity in vivo. The purpose of this study is to evaluate histologic response and toxicity of combination s.c. delivery of HA-DOX/HA-CIS as a significant improvement over IV delivery with standard drugs reduces dose levels and expands the therapeutic dosing range for these drugs. Methods: 1.5x10 6 MDA-MB-468LN human breast cancer cells (metastatic line) were injected into the mammary fat pad of female Nu/Nu mice. When tumors reached 6mm, mice (n=8 per group) were then treated with standard DOX/CIS IV combination therapy or s.c. injections of HA-DOX/HA-CIS at 25%,50%,75%,100%,125%, and 150% MTD for these drugs. Drugs were dosed weekly x 3 wks and tissues were collected for histology at 4 and 12wk timepoints. Results: Only the nanoconjugate groups demonstrated a complete clinical response (CR) to therapy and a complete pathologic response (CPR) histologically [CR =62.5% of mice and CPR=12.5% at 50% MTD;CR=87.5% and CPR=25% at 75%MTD; p&lt;0.0001 vs. IV groups which had no CRs and some partial responses (12.5% at 50%MTD and 25% at 75%MTD)]. HA groups had no lymphatic or bony metastases while 1 animal (12.5%) in the IV 50% MTD group had spinal metastases (p&lt;0.01). Mild cardiac and renal toxicity was noted in the 25% and 50% MTD IV groups respectively while no cardiac or renal toxicity was observed in the HA groups (p&lt;0.01). Finally HA conjugation increased the therapeutic dose range of DOX and CIS up to 150% of standard formulation MTD. Conclusions: Subcutaneous nanocarrier-delivery of combination DOX/CIS demonstrated significantly improved tumor response with CPR and lower toxicity on histology compared to standard drugs. This delivery platform successfully treats LR and distant metastatic disease at lower doses and improves the dosing range of these drugs compared to standard agents.
The Rising Price of Naloxone — Risks to Efforts to Stem Overdose Deaths
Authors: Ravi Gupta, Nilay D. Shah, Joseph S. Ross
Journal: New England Journal of Medicine (2016)

As experts and public officials have called for expanding the use of naloxone to reverse opioid overdoses, its price has risen dramatically. Though its relatively slow adoption may be due largely to stigma and lack of familiarity, another reason may be the cost.
Comparison of Clostridium Difficile Associated Diarrhea Detection by Enzyme Linked Immunosorbent Assay (EIA) and Polymerase Chain Reaction (PCR) in Autologous Hematopoietic Stem Cell Transplant (AHSCT) Recipients
Authors: Kenneth Utz, Christopher Frei, Bonita Neumon, Brenda L. Frye, Deanna Schneider, David J Haile, Cesar O. Freytes
Journal: Blood (2011)
Invasive Mycoses in High-Risk Cancer Patients - a Prospective Analysis of Clinical Parameters, Side Effects, Drug Interactions and Costs for the Safe and Economically Appropriate Use of Systemic Antifungal Agents.
Authors: Werner Neubauer, Alf Zerweck, Alexandra Goebel, Beate Lubrich, Hartmut Bertz, Monika Engelhardt
Journal: Blood (2009)
Therapeutic response to induction chemotherapy and prognosis of patients with inflammatory breast cancer in respect to HER2 and hormonal status.
Authors: D. Kolarevic, Z. Tomasevic
Journal: Journal of Clinical Oncology (2011)

e11517 Background: IBC presents the most aggressive form of BC with high incidence of HER2 positivity (+) and low rate of complete remission to induction chemotherapy (iCT). It is initially inoperable and the only identified prognostic factor is clinical response to iCT. The aim of this retrospective analysis is to evaluate the response rate and prognosis of HER2+ and triple negative (TN) IBC patients. Methods: We evaluated 84 medical records of patients with IBC, without distant metastases, registered at Institute for Oncology and Radiology of Serbia in period 2008- 2010. IBC is defined as BC with typical clinical signs of cancer-mastitis, with or without pathologically confirmed skin lymphangiosis and with or without underlying tumour. Responses have been evaluated clinically and by mammography after 4 cycles of iCT. CR was estimated as a complete disappearance of previously palpable breast tumour, no clinical and mammography signs of cancer mastitis and no enlarged regional lymph nodes. Results: The incidence of HER2+IBC was 47% and TN IBC 19%. Median age at diagnosis was 57 and 54 years, respectively. Skin lymphangiosis was confirmed in 45% (HER2+) and 19% (TN). There were 18% of pts in HER2+IBC reported presence of positive family history and none in TN IBC. All patients received anthracycline-based iCT, without concurrent trastuzumab or hormonal therapy. CR or PR to iCT was observed in 78% of HER2+IBC patients versus 62% in TN IBC. After operation (performed in 58% and 56%), pathological CR and PR were found in 83% HER2+ compared to 33% TN IBC. Disease progression was detected in 25% vs. 44%. 8% of HER2+ and 25% of TN patients died, while OS was 27,3 and 13,75 months in these two groups of IBC respectively. Conclusions: In this study we showed that triple negative is more aggressive form of IBC than HER2+, with lower clinical and pathological response rate to iCT, shorter time to disease progression, higher mortality and decreased overall survival. While HER2+ patients have the option of trastuzumab and/or hormonal therapy as additional, the more effective treatment should be considered in treatment of TN IBC patients.
Clinicopathologic findings in Jamaican men with prostate cancer.
Authors: L. J. Kampel, K. Tse, M. Joseph
Journal: Journal of Clinical Oncology (2011)

214 Background: Jamaican men appear to have higher age adjusted incidence rates (302/100K) than African Americans (250/100K) and Caucasians (182/100K). The purpose of this study is to examine the clinicopathologic findings in Jamaican born men presenting to Memorial Sloan-Kettering Cancer Center over a five-year period. Methods: We reviewed the records of 150 Jamaican-born men seen at MSKCC for prostate cancer between 2003 and 2008. Age at diagnosis, highest pretreatment PSA levels, Gleason scores, and clinical stage were tabulated. Pathologic T and N stage was included for patients undergoing prostatectomy. Results: 23 patients were excluded because the diagnosis of prostate cancer was not confirmed. The mean age at diagnosis was 59 years (37-77). The median PSA was 8 ng/mL (1-7,400 ng/mL). The distribution of Gleason scores was Gleason 6: 51 patients (40%), Gleason 7: 57 patients (45%), and Gleason 8-10: 19 patients (15%). 92% (75/81) of the men had organ confined disease by (cT1-2) by DRE. Of 46 men who had prostatectomy, 31 (67%) had organ confined disease (p T2) and 84% (37/44) were node negative. Conclusions: Without a comparison cohort, no firm conclusions can be drawn. But, Jamaican born men presenting to MSKCC for treatment of prostate cancer do not seem to have unusually adverse pretreatment characteristics or more advanced pathological findings at prostatectomy. Our results may be affected by referral bias in favor of patients with lower risk disease. Further research is needed to determine if Jamaican men with prostate cancer present with more advanced stage or higher grade disease than men in the general population. No significant financial relationships to disclose.