tbuckley/cabot-search huggingface dataset:
Treating multiple cancers with the human anti-cancer heterologous bi-vaccine (TLNGIS).
Authors: Shuajp Kraja
Journal: Journal of Clinical Oncology (2017)

e14633 Background: Genomic segments of oncogenic viruses, when found inside healthy cell nuclei, can induce changes in the cell’s own genome during division, creating a transmittable change of genetic information. The new malignant cells thus created are recognized as foreign and destroyed by cellular immunity Thymuslymphocytes. Otherwise, unrecognised by the immune system and allowed to breed abnormally, such cells result in a malignant tumour mass, diagnosed as cancer. Based on this original theoretical explanation, we achieved the successful synthetization of a human heterologous anticancer Bi-Vaccine, further successfully confirming its prophylactic and curative abilities through the laboratory and clinic treatment of voluntary patients. Methods: Thymuslymphocytes, prepared though in indoor in vitro cultures and equipped with new and selective genetic information, acquire the ability to recognize cancerous cells as foreign cells, destroying them anywhere in the human body.The Bi-vaccine has been produced as the union of two vaccines: 1.the antitoxin, anti-tumour vaccine which destroys free toxins in the blood stream and in the pertinent cancerous cells; and 2.the thymus lymphocytic vaccine, equipped with new selective genetic information to destroy malignant tumour cells. Results: Thus the Bi-vaccine cures cancer until complete healing and protects subjects of all ages against the uncontrolled growth of malignant cells. The Bi-vaccine is produced in its live and dry state. Results: Over the years, there are treated and cured hundreds of voluntary patients with various forms of cancer. Successful healing in casses with advanced cancer (incurable casses). The Bi-vaccine is patented by European patents office-EP 1523991B1 as an anti-cancer vaccine "Human Heterologous Anti-Cancer Bi-Vaccine”. Conclusions: After more studies of several decades of all cases with different forms of cancer, treated with the “Bi-vaccine”has confirmed a complete success in various forms of cancer. The complementary (TLNGIS) cell to fight globally cancer. Prof. Dr. Shuajp Kraja, molecular biologist/Director of IIB Tirana, Albania Clinical trial information: EP523991 B1.
Pathological response to neoadjuvant gemcitabine plus nabpaclitaxel in pancreatic adenocarcinoma to improve survival.
Authors: Rafael Alvarez-Gallego, Antonio Cubillo, Elena Garralda, Estela Vega, Jesus Rodriguez-Pascual, Lisardo Ugidos, Emilio De Vicente, Yolanda Quijano, Carmen Rubio, Ovidio Hernando, Carlos Plaza, Fernando Lopez-Rios, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2016)

4109 Background: nab-paclitaxel + gemcitabine is approved for the treatment of metastastic pancreatic cancer. So far, few studies have investigate this regimen in patients with nonmetastatic disease. Here we describe our experience of using gemcitabine and nab-paclitaxel as neoadjuvant. Methods: Patients with resectable, borderline resectable or locally advanced pancreatic cancer were treated with gemcitabine (1000mg/m2 days 1, 8 and 15) and nab-paclitaxel (125mg/m2 days 1, 8 and 15) as neoadjuvant treatment. Some patients were treated also with chemoradiotherapy after completion of chemotherapy treatment. Response were assessed by FDG-PET, CA199 levels and EUS-elastography. Results: 58 patients were included into the study and treated wit gemcitabine plus nab-paclitaxel. The median number of cycles were 3 (range 2-14). At diagnosis 15 patients presented with resectable disease, 16 with borderline tumors and 27 patients had locally advanced cancer. Twenty-four patients received treatment with chemo-radiotherapy after chemotherapy and 35patients (60%) underwent surgery (12 resectable, 8 borderline and 15 with locally advanced cancer). Poor pathological tumor response, defined by Ryan Grade Regression Tumor (GRT) grade 2 or 3, was found in 18 patients and 17 had good pathological response (GRT grade 0 or 1). Seventeen patients presented progression disease during neoadjuvant treatment and 6 patients were inoperable. Median overall survival (mOS) and progression free survival (PFS) was 16.6 months (m) and 8,8 m respectively for the entire population. In resected patients mOS and PFS were 17,4 and 13,8 m respectively. mOS was 30,6 m in patients with good pathological and 16,5 m in poor responding patients (p = 0.008). Likewise, PFS was 16,6 m in patients with good pathological response versus 8,9 m in poor responding patients (p = 0,019). In a multivariate analysis no treatment with chemoradiotherapy (p = 0.006) and good GRT (p = 0.006) impacts in overall survival. Conclusions: Neoadjuvant treatment with gemcitabine plus nab-paclitaxel improve PFS and OS in patients with non metastatic pancreas adenocarcinoma who undergo surgery and show a good pathological responding tumor.
A phase 3, randomized study of pracinostat (PRAN) in combination with azacitidine (AZA) versus placebo in patients ≥18 years with newly diagnosed acute myeloid leukemia (AML) unfit for standard induction chemotherapy (IC).
Authors: Guillermo Garcia-Manero, Chun Yew Fong, Adriano Venditti, Silvia Mappa, Riccardo Spezia, Lionel Ades
Journal: Journal of Clinical Oncology (2018)

TPS7078 Background: AML is associated with poor survival rates in patients ineligible for IC or stem cell transplant due to advanced age, comorbidities, and/or disease risk factors. Non-intensive therapies, including the hypomethylating agent AZA, are frequently used in this setting; however, response rates/survival remain dismal. Pre-clinical studies in myeloid malignancies indicate that inhibition of DNA hypermethylation and histone deacetylation induces re-expression of silenced genes in a synergistic fashion. In a Phase 2 study in AML patients ≥65 years not eligible for IC, PRAN, a novel oral histone deacetylase (HDAC) inhibitor, in combination with AZA showed promising efficacy (Garcia Manero, Blood 2016) with a 64% overall response rate and 19.1 months median overall survival. Methods: This phase 3, randomized, double-blind study (NCT03151408) is evaluating the efficacy and safety of PRAN plus AZA in patients ≥18 years with newly diagnosed AML unfit to receive IC. Ineligibility for induction CT is based on either 1) age ≥75 years or 2) age < 75 years plus a protocol-defined comorbidity. A total of 500 patients (randomized 1:1 to either PRAN + AZA or placebo + AZA) are planned to be enrolled at ~130 study centers worldwide. Randomization is stratified by cytogenetic risk (intermediate vs. unfavorable-risk) and ECOG Performance Status (0-1 vs. 2). Treatments are administered as 28-day cycles, with PRAN/placebo given orally 3x/week for 3 weeks followed by one week off and AZA administered for 7 days of each cycle. Study treatment is to be continued until disease progression or unacceptable toxicity. A minimum of 6 cycles may be required to achieve a CR. The primary endpoint is overall survival; secondary endpoints include morphologic and cytogenetic CR rates, CR without minimal residual disease and transfusion independence. Overall survival will be tested for superiority of PRAN using the stratified log-rank test at the alpha = 0.025 level of significance (one-sided). Enrollment opened in July 2017. Clinical trial information: NCT03151408.
Chemotherapy for patients with non-resectable pancreatic cancer with additional chemo-radiotherapy for patients with potentially resectable tumours: Final Results.
Authors: Per Pfeiffer, Morten Ladekarl, Michael Bau Mortensen, Anna-Lene Fromm, Jon Kroll Bjerregaard
Journal: Journal of Clinical Oncology (2016)

e15725 Background: Locally advanced pancreatic cancer (LAPC) is often a mix of borderline and never-resectable tumors. Multimodality treatment might downstage these tumors to allow a potential radical resection, especially the borderline group. In this ongoing phase II study we examined the feasibility of FOLFIRINOX with or without CRT followed by surgery for both borderline and never-resectable tumors (NCT-01397019). Methods: Patients in performance status 0-1, with initially non-resectable stage II/III pancreatic cancer were offered FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2+ 2400 mg/m2) every 14 days. Every 4th series the patients were evaluated and offered CRT (50.4 Gy/27F & capecitabine) if deemed potentially resectable. Resections were performed if deemed possible by the MDT. Results: Between August 2012 and present, 59 patients have been recruited with a median observation time of 17.4 months. Median age was 65(range 38-75) years, with 40%/60% stage II/III distribution. Median CA19-9 was 268(range 1-13,432). Three-hundred-sixty-two courses of FOLFIRINOX have been given, with a median of 6.0 per patient, with a median of 2 without dose modifications. Presently twenty-two patients have been treated with CRT. Six-teen patients have been resected, of which 8 received prior CRT. Median survival for all patients was 21.1 months (14-NR) with a 1-year survival of 74% (58-85). For patients not resected the median survival was 14.1 months (10-16) for resected the median survival has not yet been reached. The FOLFIRINOX was associated with adverse events similar to what is expected in metastatic patients. Conclusions: FOLFIRINOX with or without CRT in patients with LAPC shows promising efficacy in patients with both borderline and never-resectable tumors. Unmodified FOLFIRINOX had acceptable toxicity, however dose reductions are often needed. CRT following initial FOLFIRINOX was feasible and without unexpected toxicity. Clinical trial information: NCT-01397019.
TCT-138 Comparison Between Traditional and Guide Catheter Extension Reverse CART: Insights From the PROGRESS-CTO Registry
Authors: Iosif Xenogiannis, Dimitri Karmpaliotis, Khaldoon Alaswad, Farouc Amin Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Philip Dattilo, Catalin Toma, A.J. Conrad Smith, Barry Uretsky, Oleg Krestyaninov, Dmitrii Khelimskii, Elizabeth Holper, R. Michael Wyman, David Kandzari, Santiago Garcia, Ioannis Tsiafoutis, Wissam Jaber, Habib Samady, Jeffrey W. Moses, Nicholas Lembo, Manish Parikh, Ajay Jayant Kirtane, Ziad Ali, Darshan Doshi, Imre Ungi, Peter Tajti, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
Accuracy of the prediction of the distant recurrence risk of patients with ductal luminal breast cancer based on clinical factors versus prediction based on oncogenic mutations or gene expression.
Authors: David Demanse, Dominique Pinet, Christian Eisen, Lellean Jebailey, Wolfgang Hackl
Journal: Journal of Clinical Oncology (2018)

e12585 Background: Luminal breast cancer is not a uniform cancer type, but a heterogeneous group of disease subtypes characterized by own clinical, pathologic, biologic and genetic characteristics. Traditionally clinical-pathologic (CP) variables have been used to guide the use of endocrine treatment and/or chemotherapy to inform the choice of systemic adjuvant therapy for patients with early stage breast cancer. More recently gene expression profiling of tumours has been applied to aid doctors in personalizing treatment decisions. In the retrospective study presented here we worked with ER and/or PR positive, HER2 negative ductal breast cancers of the METABRIC collection (N = 1.104) to determine the prediction accuracy (PA) of different distant recurrence risk (DDR) prediction methods used in clinical practice. Methods: CP and genomic variables (oncogenic mutations/CNV, gene expression) were used to develop a prognostic model for disease free survival using a robust statistics approach combined with cross-validation methodology. The PA of the different sets of information was assessed using time-dependent ROC curves. Results: The average PA at 5 years was 68% for the model based on CP variables (tumour size, differentiation, nodal status, age) alone, whereas the PA values for genetic (Foundation Medicine T5-panel) or transcriptomic variables alone (20.000 genes of cBioPortal) were 55% and 60%, respectively. Amongst all mutations tested (286 oncogenic driver mutations, 19 select gene re-arrangements) only TP53 loss-of function (LoF) mutation turned out to be a covariate predictive of high DRR. Neither TP53 LoF mutation nor any of the other genetic or transcriptomic variables impacted the accuracy of DDR predictions based on CP parameters significantly. Conclusions: Collectively our study illustrates that predictions of DRR in patients with ductal luminal breast cancers based on CP parameters, mutations or transcriptomic profiles alone are highly discordant, suggesting that CP prediction models are more accurate and reliable than predictions based on mutations or by gene expression profiling.
Abstract 17299: Extracellular Annexin A2 Promotes Trypanosoma cruzi Cardiotropism
Authors: Conrad L Epting, Mashael F Alqahtani, Nga Y Du, David P Sullivan, David M Engman
Journal: Circulation (2014)

Introduction: Chagas heart disease, caused by infection with Trypanosoma cruzi, is a leading cause of heart failure in the Western Hemisphere. T. cruzi has a propensity to infect the heart, causing a progressive inflammatory cardiomyopathy, yet the basis for cardiac-specific disease remains unclear. In an attempt to understand tissue targeting, we isolated proteins at the cardiomyocyte-T. cruzi interface, revealing a novel interaction between annexins and T. cruzi trypomastigotes. Hypothesis: We hypothesized that extracellular annexin A2 interactions contribute to association with T. cruzi. Methods: Isolated membranes from murine cardiomyocytes were labeled, solubilized, and incubated with parasites as the affinity reagent. Membrane proteins that associate with parasites were pulled down and identified by mass spectrometry, revealing annexin A2 as a major component. The contribution of the annexin-parasite interaction during infection was tested through annexin A2 antibody blockade in our primary cell in ...
Validity of clinical information for a novel cancer care quality program.
Authors: John Barron, Jennifer Malin, Alex Ganetsky, David M Kern, Bingcao Wu, Ozgur Tunceli, Vincent J Willey, Ralph A. Quimbo, Michael Fisch, Joseph Singer, Ronac Mamtani
Journal: Journal of Clinical Oncology (2016)

e18003 Background: Through Anthem’s Cancer Care Quality Program (CCQP), oncologists can submit requests and accompanying clinical rationale for cancer treatments. Qualifying treatments within evidence-based pathways are eligible for enhanced reimbursement. The accuracy of clinical information within the CCQP is vital to the program’s overall effectiveness. This study evaluated the validity of the clinical information submitted to the CCQP compared with medical records of lung cancer patients obtained from treating providers. Methods: Data elements obtained relevant to this study include cancer type, stage, histology, and biomarkers (ie, ALK and EGFR mutation status). A sample of 200 lung cancer patients with CCQP requests for treatment within the HealthCore Integrated Research Environment (HIRE) – Oncology data were identified for medical record collection and review by a blinded board certified oncology pharmacist. Statistical measures of validity (agreement, positive & negative predictive value (PPV & NPV), sensitivity, and specificity) were used to compare clinical information between data sources. Results: Approximately 1300 patients with lung cancer were identified in the first year of the program (Jul 2014 – Jun 2015). Of the 200 records reviewed, 197 were confirmed to be lung cancer (PPV of 0.99) and 87% were identified as non-small cell lung cancer (NSCLC). All performance measures were ≥ 0.85, with the exception of the PPV for ALK status. Conclusions: Overall, the high agreement between the data entered for the CCQP and medical records support the validity of the clinical information for purposes of effective program implementation, administration, and research. Measures of validity (95% confidence intervals). Variable n* Agreement PPV NPV Sensitivity Specificity Stage (all) 194 0.90 (.86 - .94) - - - - Stage (NSCLC) 151 0.92 (.88 - .96) - - - - Histology 174 0.97 (.94 - .99) 0.92 (.81 - 1.00) 0.97 (.95 - 1.00) 0.85 (.71 - .98) 0.99 (.97 - 1.00) ALK mutation status 74 0.92 (.86 - .98) 0.54 (.27 - .81) 1.00 (1.0 - 1.0) 1.00 (1.0 - 1.0) 0.91 (.84 - .98) EGFR mutation status 69 0.97 (.93 - 1.00) 0.87 (.69 - 1.00) 1.00 (1.0 - 1.0) 1.00 (1.0 - 1.0) 0.96 (.92 - 1.00) *n includes the number of patients with observable data in both data sources
Outcomes, characteristics and molecular profile of myeloid sarcoma: single center experience over 13 years.
Authors: Varinder Kaur, Arjun Swami, Pooja Motwani, Daisy Alapat, Laura Fulper Hutchins, Yogesh Jethava
Journal: Journal of Clinical Oncology (2016)

e18517Background: Myeloid Sarcoma(MS) is characterized by extramedullary infiltration with immature myeloid cells. Due to rarity of MS, its clinical characteristics and outcomes are yet to be clari...
Preventing Cognitive Decline in Black Individuals With Mild Cognitive Impairment
Authors: Barry W. Rovner, Robin J. Casten, Mark T. Hegel, Benjamin Leiby
Journal: JAMA Neurology (2018)

Mild cognitive impairment (MCI) is a transition state between normal cognitive aging and dementia that increases the risk for progressive cognitive decline. Preventing cognitive decline is a public health priority.To determine whether behavioral activation prevents cognitive and functional decline over 2 years in black individuals with MCI.Single-center, single-masked, attention-controlled randomized clinical trial. Participants were enrolled from June 21, 2011, to October 3, 2014, and follow-up ended December 13, 2016. Community-based recruitment and treatment of black individuals older than 65 years with amnestic MCI. Volunteer sample of 1390 persons with memory complaints were screened. Overall, 536 individuals had baseline assessment, and 315 (58.8%) were ineligible, most often owing to normal cognition (205 of 315 [65%]) or dementia (59 of 315 [18.7%]); 221 fully eligible participants were randomized. Analyses were intention to treat.Participants were randomized to behavioral activation, which aimed to increase cognitive, physical, and social activity (111 [50.2%]), or supportive therapy, an attention control treatment (110 [49.8%]).The prespecified primary outcome was a decline of 6 or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised assessed at 6, 12, 18, and 24 months. The secondary outcome was functional decline.Of 221 randomized participants (mean [SD] age, 75.8 [7.0] years, 175 women [79%]), 77 behavioral activation participants (69.4%) and 87 supportive therapy participants (79.1%) had 2-year outcome assessments. After baseline, behavioral activation participants engaged in significantly more cognitive activities than supportive therapy participants. The 2-year incidence of memory decline was 1.2% (95% CI, 0.2-6.4) for behavioral activation vs 9.3% (95% CI, 5.30-16.4) for supportive therapy (relative risk, 0.12; 95% CI, 0.02-0.74; P = .02). Behavioral activation was associated with stable everyday function, whereas supportive therapy was associated with decline (difference in slopes, 2.71; 95% CI, 0.12-5.30; P = .04). Rates of serious adverse events for behavioral activation and supportive therapy, respectively, were: falls (14 [13%] vs 28 [25%]), emergency department visits (24 [22%] vs 24 [22%]), hospitalizations (36 [32%] vs 31 [28%]), and deaths (7 [5%] vs 3 [4%]).Behavioral activation prevented cognitive and functional decline, but this finding requires further investigation. Black individuals have almost twice the rate of dementia as white individuals; behavioral activation may reduce this health disparity.ClinicalTrials.gov Identifier: NCT01299766.
Rational drug combination therapy for improved efficacy and delayed resistance in triple negative breast cancer.
Authors: Rabia Gilani, Eric Lachacz, Li Wei Bao, Sameer Phadke, Matthew Soellner, Sofia Merajver
Journal: Journal of Clinical Oncology (2018)

e13113 Background: Single-agent targeted therapies are prone to early resistance and thus, rational drug combinations are sought. We hypothesize that combining targeted therapies will have reduced resistance compared to single agents, while also drastically improving efficacy in both sensitive and resistant tumor cells. To achieve this maximum benefit, combination therapies must be based on strong molecular and signaling evidence. While we have achieved potent single agent activity without evidence of in vivo resistance, we have been able to produce acquired in vitro resistance to UM-164, a novel Src/p38 inhibitor being developed by our lab. Methods: To create stable triple-negative breast cancer-TNBC cell lines resistant to UM-164, MDA-MB231, SUM 149 and Vari-068 cells were exposed to low nanomolar concentration of the drug. Surviving cells were grown in the presence of drug and then systematically exposed to higher concentrations of UM-164. This process was repeated until each cell line was resistant to UM-164 (defined as GI50 > 1 micro molar). Results: Significant morphology and cell signaling changes occurred in the drug-resistant cell lines. Crucially, in drug resistant cell lines the activation of c-Src and/or p38 does not return in the presence of UM-164, suggesting that resistance is not occurring via constitutive activation enabling mutations of c-Src/p38 kinases. However, compared to their drug-sensitive counterparts, the UM-164-resistant cells have significantly activated MEK1/2 and ERK1/2 signaling when treated with UM-164. Thus, we tested combinations of UM-164 + MEK1/2 inhibitors in TNBC cell lines and patient derived xenografts. We found that trametinib ( FDA-approved inhibitor of MEK1/2) is synergistic (Chou-Talalay CI at ED90 = 0.4, CI < 1 denotes synergy) with UM-164 to inhibit the growth of UM-164-resistant MDA-MB-231 and SUM-149 cell lines Conclusions: These results support our hypothesis that activation of MEK/ERK signaling can act as an escape mechanism that leads to resistance to UM-164 which can be overcome by rational combinations aimed at this adaptation. Future research into rational combinations of targeted therapies may hold the key to improving survival in TNBC.