tbuckley/cabot-search huggingface dataset:
Molecular Pathways: The Necrosome—A Target for Cancer Therapy
Authors: Lena Seifert, George Miller
Journal: Clinical Cancer Research (2016)

Abstract Necroptosis is a caspase-8–independent cell death that requires coactivation of receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) kinases. The necrosome is a complex consisting of RIP1, RIP3, and Fas-associated protein with death domain leading to activation of the pseudokinase mixed lineage kinase like followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma, and several hematologic malignancies. Preclinical data suggest that targeting this complex can have differential impact on tumor progression and that the effect of necroptosis on oncogenesis is cell-type and context dependent. The emerging data suggest that targeting the necrosome may lead to immunogenic reprogramming in the tumor microenvironment in multiple tumors and that combining therapies targeting the necrosome with either conventional chemotherapy or immunotherapy may have beneficial effects. Thus, understanding the interplay of necroptotic cell death, transformed cells, and the immune system may enable the development of novel therapeutic approaches. Clin Cancer Res; 23(5); 1132–6. ©2016 AACR.
Added Value of Combined Semi-Quantitative and Visual [123I]FP-CIT SPECT Analyses for the Diagnosis of Dementia With Lewy Bodies
Authors: Nicolas Nicastro, Valentina Garibotto, Gilles Allali, Frederic Assal, Pierre R. Burkhard
Journal: Clinical Nuclear Medicine (2016)

To assess the validity of a semi-quantitative I-FP-CIT SPECT method, compared to the commonly used visual analysis, in patients with probable dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also studied DLB specific uptake impairment pattern and correlation of uptake in the presence or absence of parkinsonism.Among 1202 scans performed at our center from 2003 to 2015, we identified 93 subjects with probable DLB (mean age 76.9 ± 6.8 years, 37% women) and 18 with AD (mean age 76.9 ± 8.1 years, 50% women). Independent visual and semi-quantitative assessments based on previously established on-site reference values (including volumes-of-interest uptake, caudate-to-putamen ratio and striatal asymmetry index) were performed and compared between both groups.Visual staging was considered abnormal in 96.8% of DLB patients, whereas 97.8% of subjects had an abnormal semi-quantitative assessment. Combining both methods yielded a 100% sensitivity. Patients with DLB exhibited a more pronounced impairment of putaminal uptake when associated with parkinsonism, whereas a more diffuse pattern and significantly higher uptake values were observed in the subgroup of DLB patients without parkinsonism (resp. striatal uptake 1.61 ± 0.66 vs. 2.28 ± 0.52, P = 0.01). A minority of AD subjects show minimal alterations of presynaptic dopaminergic transport (striatal uptake 3.07 ± 0.41), values being always significantly higher than those from DLB patients, irrespective of the presence of parkinsonism (P < 0.0001) or not (P = 0.002).Additional use of semi-quantitative analysis allows a higher discrimination of DLB from AD and demonstrates a specific pattern of degeneration in DLB patients according to their motor phenotype.
Restoration of Peroxiredoxins and Catalase Is Closely Correlated with the Level of Philadelphia Chromosome during Imatinib Therapy in CML.
Authors: Kyoung-Eun Lee, Hyun-Ae Woo, Seoug-Ha Yang, Jung-Won Huh, Moon Young Choi, Hye Jung Chang, Jee-Young Ahn, Soo Ah Oh, Yeung-Chul Mun, Eun-Sun Yoo, Sue Goo Rhee, Chu-Myong Seong
Journal: Blood (2007)
Everolimus therapy for angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: Results from EXIST-2.
Authors: John J. Bissler, J. Chris Kingswood, B. A. Zonnenberg, Michael Frost, Elena Belousova, Elzbieta Radzikowska, Michael Fischereder, Norio Nonomura, Susan Brakemeier, Petrus de Vries, Tarek Sahmoud, Gaurav Shah, Sara Miao, Diep Gray, Klemens Budde
Journal: Journal of Clinical Oncology (2012)

356 Background: We evaluated everolimus, an oral mTOR inhibitor, for treating angiomyolipoma (AML) in patients with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM). Methods: EXIST-2 ( NCT00790400 ) is a prospective, international, randomized, double-blind, placebo-controlled, phase III study. Patients (≥1 AML with longest diameter ≥3 cm) were stratified by (i) TSC and enzyme-inducing anti-epileptic drug (EIAED) use, (ii) TSC and EIAED non-use, (iii) sLAM and randomized 2:1 to receive everolimus 10 mg daily (n=79) or placebo (n=39). Kidney CT/MRI was performed at baseline, at 12, 24, and 48 weeks, and then annually. Primary efficacy endpoint was the proportion of patients with AML response (best overall confirmed ≥50% reduction in sum of volumes of all target AML relative to baseline). Secondary efficacy endpoints included time to AML progression and skin lesion response rate in patients with &gt;1 skin lesion at baseline (n=114). Adverse events (AE) were monitored every visit. Core phase results (6 months from last patient randomized) are presented. Results: Patient characteristics were balanced across the 2 groups; median patient age was 31 years. Median treatment duration was 38.1 weeks (everolimus) and 34.0 weeks (placebo). Everolimus best overall response rate (41.8%) was superior to placebo (0%) for the primary efficacy endpoint (p&lt;0.0001). Median time to AML progression was 11.4 months for placebo and was not reached for everolimus. The everolimus group had a significantly higher best overall skin lesion response rate (complete or partial response) than placebo (26% vs. 0%; p=0.0002). Everolimus was associated with an acceptable safety profile consistent with previous reports in TSC, with most AEs being grade 1 or 2. Serious AE incidence was similar in the treatment arms (everolimus 19.0% vs. placebo 17.9%). Conclusions: Everolimus treatment produced a clinically and statistically significant reduction in AML volume compared with placebo and showed a safety profile consistent with previous reports. Everolimus represents the first potential pharmacologic treatment option for patients with AML.
99mTc-MDP Uptake in Diffuse Pleural Recurrences of Pulmonary Neuroendocrine Carcinoma
Authors: Taisong Wang, Wenli Qiao, Yan Xing, Jinhua Zhao
Journal: Clinical Nuclear Medicine (2016)

A 39-year-old woman with a history of pulmonary neuroendocrine carcinoma segmental palliative resection underwent a Tc-MDP bone scintigraphy to evaluate possible osseous metastases. The static images revealed diffuse elevated activity in the left hemithorax, more prominent in the lower thorax, which is suggestive of malignant pleural effusion. However, SPECT/CT images showed that the elevated activity was from pleura-based soft tissue masses, which were confirmed as recurrent tumor pathologically after biopsy.
A Common Genetic Variant in the 3′UTR of IRF4/MUM1 Associates with Risk of Disease and Poor Prognosis in Chronic Lymphocytic Leukaemia.
Authors: James M Allan, Nicola Sunter, Andrew Hall, Tryfonia Mainou-Fowler, Graham Jackson, Geoffrey Summerfield, Robert John Harris, Andrew Pettitt, Richard Houlston, James Bailey, Chris Pepper, Chris Fegan, Guy Pratt, David J Allsup
Journal: Blood (2008)
Cardiometabolic risk markers, adipocyte fatty acid binding protein (aFABP) and the impact of high-intensity interval training (HIIT) in obese adolescents
Authors: Susann Blüher, Jakob Käpplinger, Sabine Herget, Sandra Reichardt, Yvonne Böttcher, Andrea Grimm, Jürgen Kratzsch, David Petroff
Journal: Metabolism (2016)
Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory
Authors: Joshua Jacobs, Jonathan Miller, Sang Ah Lee, Tom Coffey, Andrew J. Watrous, Michael R. Sperling, Ashwini Sharan, Gregory Worrell, Brent Berry, Bradley Lega, Barbara C. Jobst, Kathryn Davis, Robert E. Gross, Sameer A. Sheth, Youssef Ezzyat, Sandhitsu R. Das, Joel Stein, Richard Gorniak, Michael J. Kahana, Daniel S. Rizzuto
Journal: Neuron (2016)
Clinical availability of endoscopic submucosal dissection for patients with local failure after chemoradiotherapy for esophageal squamous cell carcinoma.
Authors: Kyoko Inadomi, Masayuki Watanabe, Yohei Nagai, Koichi Nonaka, Koichi Sakurai, Satoshi Ida, Shiro Iwagami, Masaaki Iwatsuki, Yoshifumi Baba, Yuji Miyamoto, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

118 Background: Local failure after chemoradiotherapy (CRT) remains a major problem for patients with esophageal squamous cell carcinoma (ESCC), and there are few curative treatment options available in such cases except salvage esophagectomy. The aim of this study is to demonstrate the clinical efficacy and safety of endoscopic submucosal dissection as a salvage therapy (salvage ESD) for local failure after CRT. Methods: Between 2007 and 2011, 66 patients underwent ESD for superficial ESCC in our hospital. Five of these patients underwent salvage ESD for local failure after CRT, and were reviewed retrospectively. They were treated with CRT, consisting of 60 Gy irradiation and concurrent chemotherapy. The indications for salvage ESD were as follows: 1) absence of lymph-node or distant metastasis after CRT; 2) superficial and endoscopically resectable lesion after CRT; 3) refusal by patient to undergo salvage esophagectomy; 4) written informed consent. Salvage ESD was performed using a flush knife or hook knife with a hyaluronic acid injection into the submucosal layer. Results: The baseline stage before CRT was as follows: T1b/T2/T3 in 3/1/1, N0/1 in 4/1, and M0/1 in 4/1 patients, respectively. These 5 patients had histologically proven local failure, and the stage after CRT was as follows: T1a/T1b in 1/4, N0/1 in 5/0, and M0/1 in 5/0 patients, respectively. Salvage ESD was performed in all patients who had en bloc resection with no complications and pathologically R0 resection. In 5 patients, 2 had a pT1a lesion, and 3 had a pT1b lesion. 1 lesion recurred in other site 3 months after salvage ESD, which was resected successfully by a second ESD procedure. Conclusions: Salvage ESD is an available option for patients with local failure after CRT for ESCC.
Common Submicroscopic Genomic Imbalances Accompany the Ph Chromosome at Diagnosis in Chronic Myeloid Leukemia
Authors: Jamshid S Khorashad, Valeria A De Melo, Heike Fiegler, Gareth Gerrard, Dan Brudzevsky, David Marin, Jane F. Apperley, John M Goldman, Letizia Foroni, Alistair G Reid
Journal: Blood (2008)
Activity of retreatment with sorafenib for metastatic renal cell carcinoma.
Authors: M. Nozawa, N. Matsumura, M. Yasuda, Y. Okuda, H. Uemura
Journal: Journal of Clinical Oncology (2011)

404 Background: Treatment options for metastatic renal cell carcinoma (mRCC) have increased. Complete remission is, however, rarely seen and patients are treated with multiple sequential therapies. We assessed clinical activity of sorafenib rechallenge after progressing on other therapies. Methods: Patients with mRCC who received a second course of sorafenib therapy after failure of prior sorafenib and other agents were retrospectively identified. RECIST-defined objective response rate and progression-free survival (PFS) and toxicity were analyzed. Results: Fourteen patients with mRCC who were retreated with sorafenib were identified and twelve patients were assessable for this study. 92% were male. Median age at first systemic therapy was 63 years. Prior nephrectomy was performed in 92% of patients. 42% of patients had favorable or intermediate risk, 17% poor, and the rest not available per MSKCC criteria. Eighty-three percent of patients were treated with other agents before initial sorafenib therapy, including 75% interferon-alpha (IFN-alpha), 50% interleukin-2 (IL-2), and 17% sunitinib. First sorafenib therapy began a median of 9.0 months after the diagnosis of mRCC and produced a clinical benefit (PR + SD) rate of 75% and a median PFS of 5.0 months. 67% of patients discontinued initial sorafenib for disease progression and 33% for adverse events. Interval between discontinuation of initial sorafenib and rechallenge was a median of 7.6 months. During the intervening period, 50% of patients were treated with sunitinib, 33% with everolimus, 25% with VEGFR1 vaccine, and others. Clinical benefit rate of 67% and a median PFS of 4.3 months were obtained on sorafenib rechallenge. There was no significant difference in outcome to sorafenib rechallenge based on duration between sorafenib treatments or number or type of intervening treatments. No new severe toxicity was observed during rechallenge. Conclusions: Sorafenib rechallenge has potential to achieve clinical benefits, is well-tolerated, and may be considered after multiple sequential therapies in select mRCC patients. No significant financial relationships to disclose.
Pentostatin and Alemtuzumab: An Immunosuppressive Nonmyeloablative Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT).
Authors: Faiz Anwer, Michael P. Carroll, Myke R. Green, Lee Cranmer, Leona Downey, Linda Garland, Katayoun Moini, Daniel O. Persky, Rachel Swart, Andrew M. Yeager
Journal: Blood (2009)
The Hemoglobin-Haptoglobin Receptor (CD163) Is Expressed by a Subpopulation of Erythroid and Granulo-Macrophagic Progenitors and Can Be Stimulated in Vitro and in Vivo by Physiological and Pharmacological Ligands to Stimulate Hematopoiesis
Authors: Kathryn Matthews, Nicole Worsham, Neeta Rugg, Jose A. Cancelas, David Bell
Journal: Blood (2012)
Long Term Outcomes of Hematopoietic Stem Cell Transplantation in Patients with Severe Phenotype Hurler Syndrome: an International Multi-Center Study
Authors: Mieke Aldenhoven, Maria Escolar, Robert Wynn, Ed Wraith, Anne O'Meara, Paul Veys, Nizar Mahlaoui, Michele Poe, Paul Orchard, Joanne Kurtzberg, Jaap J Boelens
Journal: Blood (2012)
The experience of young women diagnosed with breast cancer who undergo fertility preservation (FP) consultation.
Authors: K. A. Hill, T. Nadler, R. Mandel, S. Burlein-Hall, C. Librach, E. Warner
Journal: Journal of Clinical Oncology (2011)

249 Background: In recent years FP has been a growing concern for young women diagnosed with breast cancer. ASCO has recommended that such women be referred to a reproductive specialist as early as possible before beginning systemic adjuvant therapy. Aim: To gather information about young breast cancer patients’ experiences with FP referral, consultation, and decision making. Methods: Anonymous questionnaires were mailed to consecutive breast cancer patients referred January 2005 through January 2010 from our center to the CReATe clinic in Toronto. Topics included information about demographics, cancer stage and treatment, previous fertility problems, referral source and timing, options presented and chosen, and satisfaction with the referral, consultation and decision making processes. Results: Of the 50 women identified 26 (52%) participated. Average age of respondents was 31 (range 24-41). 17 (65%) were married or in a long-term relationship, and 9 (35%) already had 1 child. Seven (27%) were referred before surgery, 16 (62%) after surgery but before systemic therapy, 2 (8%) after starting hormone therapy, and 1 after completing chemotherapy. Only 54% opted for FP. Of the 17 (66%) who reported plans to start/add to their family prior to diagnosis of breast cancer, 53% proceeded with FP and of the 9 who did not have plans to start/add to their family 5 (55%) pursued FP. 41% had difficulty with decision making and 50% found cost to be a significant barrier. A common theme among respondents was inadequate time for decision making. Several complained about the lack of written material before and/or after their consultation. 85% felt that access to a psychosocial counselor would have been beneficial to the decision making process. 57% were satisfied or extremely satisfied overall. Conclusions: (1) If appropriate, FP referral should be initiated by the surgeon as soon as a diagnosis of invasive cancer is made. Obtaining receptor and HER2 status on core biopsy samples may identify women who will require systemic therapy and may benefit from early FP referral. (2) Women need written materials before and after FP consultation. (3) There is a major role for a FP counselor who is able to spend additional time helping with decision making.
The Polycomb Group Transcriptional Repressor Bmi-1 Is Constitutively Expressed in Multiple Myeloma (MM) Cells and Modulates Proliferation through a Mechanism Independent of the Ink4a/ARF Locus.
Authors: Frank J. Desarnaud, Masood Shammas, Paola Neri, Hemanta Koley, Rao Prabhala, Li Cheng, Suk Kim Ryung, Dharminder Chauhan, Pierfrancesco Tassone, Jooeun Bae, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2004)
A phase I study of neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel, doxorubicin, and cyclophosphamide (NAC) in patients with stages II-III HER2-negative breast cancer.
Authors: H. T. Khong, D. L. Dyess, T. W. Butler, T. L. Dumlao
Journal: Journal of Clinical Oncology (2011)

e11519^ Background: The TAC regimen (docetaxel, doxorubicin, and cyclophosphamide) is among the most active drug combinations in the adjuvant and neoadjuvant settings. A recent study demonstrated that weekly nab-paclitaxel (N) is superior to every-three week docetaxel in both efficacy and toxicity in patients with metastatic breast cancer. Here we report results of a single center phase I study in which nab-paclitaxel replaces docetaxel in the conventional TAC regimen. Methods: Women with HER-2 negative stages II-III breast cancer were enrolled. Eligible patients received 6 cycles of the NAC regimen: nab-paclitaxel (100-150 mg/m2, days 1 and 8), doxorubicin (50 mg/m2, day 1), and cyclophosphamide (500 mg/m2, day 1). Peg-filgrastim was given on day 9. Results: Sixteen patients have enrolled thus far, one of which was a screen failure. Median tumor size was 6 cm. Median age was 54 years (40-69). ER+ tumors accounted for 53%, and 47% were triple negative. There were two inflammatory breast cancer. After the first three patients on dose level 0 (N of 100 mg/m2, weekly 5 on 1 off, Q 6 weeks) experienced several dose delays because of grades 3 and 4 neutropenia, the protocol was amended such that dose level -1 (N of 100 mg/m2, weekly 2 on 1 off, Q 3 weeks) would be the new starting point and there would be no further dose escalation. There was no DLT. To date, a total of 57 cycles of dose level -1 were given. 43.8% required dose delay. There were two episodes of febrile neutropenia. The cCR by physical examination was 93.3%. One patient had a minimal response. The median number of cycles required before a cCR was 2. Even though pCR was not a primary end point, we observed a very favorable pCR rate. Eight patients already underwent surgery. The pCR rate for this group was 50%. Another patient had a near pCR, with microscopic residual disease. The pCR for the 4 triple negative patients was 100%. Conclusions: This single center phase I study demonstrates safety and dramatic activity for the neoadjuvant NAC regimen in patients with stages II-III HER-2 negative breast cancer. This regimen seemed highly effective with impressive clinical and pathologic complete responses.
Influence of body mass index (BMI) on PSA kinetics in castrate-resistant prostate cancer (CRPC).
Authors: M. Teo, N. J. Mayer, N. Khan, J. P. Sweeney, S. O'Reilly, D. G. Power
Journal: Journal of Clinical Oncology (2011)

209 Background: Understanding of the role of host energetics in cancer outcomes has been increasing in recent years. In early stage prostate cancer trials obesity is associated with worse outcome. Its effect on treatment response and survival in advanced disease is largely unexplored. We sought to explore the relationship between BMI, the most validated measure of obesity, and biochemical response as well as overall survival in patients receiving first-line chemotherapy. Methods: We reviewed a prospectively-maintained institutional database identifying patients who received docetaxel (D) for CRPC. Demographics and PSA levels during treatment were extracted. Pts were divided into 2 BMI groups (&gt; and &lt; 30 kg/m 2 ). We calculated biochemical responses as per historically validated surrogates: PSA decrease &gt; 30% at 3months; overall decrease &gt; 50%; time to PSA nadir and PSA half-life after 4 cycles, for each group. Results were compared with unpaired t-test and chi-square test. Results: 33 pts were identified between June ‘04 and Sept ‘10, 16 pts with BMI &gt; 30 (hBMI) (range 30.1-34.2) and 17 with BMI &lt; 30 (nBMI) (21.5-29.6). Median age for the entire cohort was 67.9 yrs (47.7-79.8), median Gleason score 8, median cycles of D received was 6 (3-20) with median duration of 3.7 months (1.4-8.7), p&gt;0.05. Baseline PSA was 89.1 ng/ml (0.34-417) and 259.2 (16.1-1,589) for hBMI and nBMI respectively, p = 0.023. For hBMI group, only 56.3% (9/16) of patients demonstrated biochemical response, compared with 88.2% (15/17) in nBMI group(p = 0.039). Of the biochemical responders, 6/16 (38%) of hBMI and 9/7 (53%) of nBMI achieved &gt;50% fall in PSA (p = 0.743) while 8/16 (50%) patients in hBMI group and 10/17 (59%) in nBMI group had a PSA drop &gt;30% at 3 months (p = 0.61); Median time to PSA nadir was 3.4 months (0.7-4.9) and 2.7 (0.7-7.5), and median PSA half life was 56.4 days (16-138) and 46.1 days (16-302) for hBMI and nBMI groups, respectively, p &gt; 0.05. Conclusions: Obese patients with CRPC have lower pre-D PSA levels. However, they also experience a lower rate of biochemical response to therapy. PSA kinetics in biochemical responders do not appear to be influenced by BMI. Survival data will be presented. No significant financial relationships to disclose.
Of Mice and Men – or a Lack of Positive Effect of Enhanced Vegetative Nervous System Tonus on Mobilization of Hematopoietic Stem and Progenitor Cells – Results in Patients with Elevated Catecholamine Level in Peripheral Blood Suffering from Acute Psychotic and Anxiety Disorders
Authors: Daniel Pedziwiatr, Jolanta Kucharska-Mazur, Ewa Suszynska, Marta Tkacz, Agata Poniewierska, Marta Budkowska, Daria Salata, Barbara Dolegowska, Jerzy Samochowiec, Mariusz Z Ratajczak
Journal: Blood (2014)