tbuckley/cabot-search huggingface dataset:
MicroRNA expression profile in HER2-positive breast cancer patients submitted to neoadjuvant chemotherapy.
Authors: Renata D. Sicchieri, Isabela C Buzatto, Daniela Pretti da Cunha Tirapelli, Willian A. Silveira, Tatiane M. G. Oliveira, Larissa R. Mouro, Valdair Francisco Muglia, Heriton M. R. Antonio, Paola Rodrigues, Jurandyr Moreira de Andrade, Daniel Guimarães Tiezzi
Journal: Journal of Clinical Oncology (2014)

e11511 Background: In the neoadjuvant setting, trastuzumab associated with chemotherapy significantly improves pathologic complete response (pCR) when compared to chemotherapy alone. There are currently no conclusive biomarkers for patient response to trastuzumab in clinical practice. We investigate predictive factors of response to neoadjuvant treatment in HER2-positive breast cancer patients. Methods: We evaluated clinical, histological and immunohistochemical characteristics of 54 patients with histologically confirmed HER2-positive, stage II and III, breast cancer, treated with preoperative trastuzumab/chemotherapy combination. MicroRNA expression profile from 8 invasive ductal carcinomas was analyzed using Human MicroRNA Cards v.3 A and B (Applied Biosystems). Samples were collected using an ultrasound guided core-needle biopsy prior to neoadjuvant treatment. Samples from patients who achieved pCR were used as basal expression level. The cards were processed and analyzed using a QuantStudio 12K-Flex System. Real-time RT-PCR data analysis was performed using StatMiner software (Integromics). We considered a significant fold change for the log10RQ < -1.0 or > 1.0 and the p-value< 0.05. Integrated miRNA expression analysis and mRNA target prediction was performed using the TargetScan software and DIANA miRPath v.2.0 software. Results: The pCR rate was 45%. Among all clinical characteristics, only the clinical stage was predictive for pCR [stage 2= 77% of pCR versus 38% in stage 3 (p= 0.03)]. Positivity to hormone receptor and histological high grade were not predictive factors of pCR (p= 0.63 and p= 0.78). We identified 16 downregulated miRNAs that significantly discriminate the resistance to therapy. The mRNA target prediction analyses have demonstrated the miRNAs mir-135b, mir-372 and mir-520h significantly target the ERBB4, VEGFA, CDKN1A and APC genes. The pathways union analysis identified these miRNAs can significantly modulate the ERBB2 and HIF-1 signaling pathways (p= 3.4e-05 and p= 2e-04). Conclusions: We have identified miRNAs mir-135b, mir-372 and mir-520h as potential candidates markers for trastuzumab resistance in HER2-positive breast cancer.
High Vs. Low-Intensity Bridging Chemotherapy in Children with Acute Lymphoblastic Leukemia Awaiting Chimeric Antigen Receptor T-Cell Therapy: A Population-Based Study from Ontario, Canada
Authors: Sumit Gupta, Sarah Alexander, Sue Zupanec, Uma Athale, Mylene Bassal, Ethan Edwards, Paul J. Gibson, Donna Johnston, Stacey Marjerrison, Alexander Zorzi, Johann K. Hitzler, Ahmed Naqvi, Angela Punnett, James A. Whitlock, Stephan A. Grupp, Shannon L. Maude, Joerg Krueger
Journal: Blood (2018)
Von Willebrand Factor (vWF) Levels and Platelet Counts Showed Strong Inverse Correlation in Calreticulin (CALR) Mutated ET, but Weak in JAK2V617F Mutated PV and ET
Authors: Kazuhide Iizuka, Noriyoshi Iriyama, Soji Morishita, Yoshikazu Iizuka, Naotake Yanagisawa, Hamada Takashi, Miharu Watanabe, Masaru Nakagawa, Yoshihito Uchino, Hiromichi Takahashi, Jun Ando, Katsuhiro Miura, Norio Komatsu, Yoshihiro Hatta, Masami Takei
Journal: Blood (2018)
Mitochondrial Transfer Confers Microenvironment-Mediated Resistance to Oxphos Inhibition in AML
Authors: Haeun Yang, Yoko Tabe, Kaori Saito, Rodrigo Jacamo, Helen Ma, Vivian Ruvolo, Junichi Imoto, Kazuho Ikeo, Kaoru Mogushi, Masaki Hosoya, Shigeo Yamaguchi, Kotoko Yamatani, Yuko Murakami-Tonami, Koya Suzuki, Takashi Miida, Michael Andreeff, Joseph R Marszalek, Marina Y. Konopleva
Journal: Blood (2018)
A phase II study comparing metronomic chemotherapy with chemotherapy (single-agent cisplatin), in patients with metastatic, relapsed, or inoperable squamous cell carcinoma of head and neck.
Authors: Vijay Maruti Patil, Vanita Noronha, Shripad Dinanath Banavali, Amit Joshi, Sachin Dhumal, Supreeta Arya, S Juvekar, Vamshi Krishna Muddu, Bharatsinha Baburao Bhosale, Pankaj Chaturvedi, Devendra Chaukar, P. S. Pai, Anil D'Cruz, Kumar Prabhash
Journal: Journal of Clinical Oncology (2014)

6017 Background: Cetuximab based regimen is the recommended palliative chemotherapy for head and neck squamous cell cancers. However, due to financial constraints, toxic intravenous chemotherapy with poor outcome is more commonly used in lesser developed countries. Retrospective studies have shown a role for oral metronomic therapy (MCT) in HNSCC especially in a resource poor setting. Methods: We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200 mg twice daily) and weekly methotrexate (15mg/m2)] to intravenous single agent cisplatin (IP) (75mg/m2) given 3 weekly. Patients with relapsed, metastatic and inoperable head and neck cancers meriting palliative chemotherapy,performance status 0-2, unaffordable for cetuximab and with adequate organ functions were eligible.. The primary end point was progression-free survival. The trial was powered to detect a 33% improvement in the median PFS, from 2.7 months for IP arm, with type 1 error of 5% and type 2 error of 80%. Univariate analysis of survival was performed using Kaplan Meier estimates with intention to treat analysis. Toxicity rates were compared using chi square test. Results: 110 patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (log-rank p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5 - 275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2 -199.8 days) (log-rank p=0.02). There were fewer grade 3/4 adverse effects wth MCT, which was nonsignificant.(18.9% vs. 31.4%, P = 0.14). Conclusions: Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting. It is a viable and cost-effective treatment option in patients not affording cetuximab. Further studies are warranted to evaluate the benefit, schedule and combination of metronomic therapy. Clinical trial information: 2014/01/006359.
Chromosomal copy number alterations (CNAs) for risk assessment of ductal carcinoma in situ (DCIS).
Authors: Anosheh Afghahi, Erna Forgo, Aya Mitani, Manisha Desai, Sushama Varma, Tina Seto, Kristin C. Jensen, Scarlett Lin Gomez, Amar K. Das, Andrew H. Beck, Allison W. Kurian, Robert B. West
Journal: Journal of Clinical Oncology (2014)

565 Background: Population-wide screening mammography has contributed to a significant increase in the diagnosis of DCIS, raising questions about over-diagnosis and over-treatment. We aimed to determine whether adding genomic variables to standard clinico-pathologic factors may identify low-risk versus high-risk DCIS, with an ultimate goal of tailoring therapy. Methods: Patient-level clinical and pathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of biopsies revealing DCIS only versus concurrent invasive breast cancer (IBC) with DCIS. We used fluorescence in situ hybridization to investigate the predictive values of CNAs of 1q, 8q24 and 11q13 (reported by The Cancer Genome Atlas to be among the most frequent CNAs in IBC) in the DCIS component of the biopsies. Multivariable logistic regression analysis was performed to describe associations with concurrent IBC, adjusting for variables including CNA frequencies, age at diagnosis, race/ethnicity, hormone receptors and grade. Results: We studied 271 patients (120 with DCIS and 151 with IBC and DCIS), most of whom were diagnosed from 2000-2003, were of Non-Hispanic White race/ethnicity, and of top statewide quintile of neighborhood socioeconomic status. We observed no differences in standard clinico-pathologic factors, including hormone receptors and grade. Compared to DCIS only, patients with concurrent IBC had higher frequencies of 2 of 3 (34.8% vs. 18%) and all 3 (10.8% vs. 4.1%) CNAs amplified; on multivariable analysis, this was the only variable significantly associated with concurrent IBC, where having 2 of the 3 CNAs was associated with a risk of IBC that was 5.28 times that of having no CNAs, and all 3 CNAs was associated with a more than 7-fold risk (P= 0.0091). Conclusions: This proof-of-concept study demonstrates the potential of CNAs to improve the identification of high-risk DCIS that is accompanied by IBC. Expanding and validating this approach may enable risk-adapted management of DCIS.
Clinical relevance of genetic mutations on treatment response to the demethylating agents in myelodysplastic syndromes.
Authors: Hyun Ae Jung, Chi Hoon Maeng, Chul Won Jung, Jun Ho Jang
Journal: Journal of Clinical Oncology (2014)

7115 Background: In the post-epigenetic therapy era, treatment approaches for patients with MDS have improved significantly over the last decade, especifically, in terms of quality of life and leukemic transformation and survival. Unlike, conventional chemotherapy, it often takes several cycles of hypomethylating agent to visualize the effect of the therapy. However, previous study had heterogenous study populations and had low response rate to hypomethylating agent. We investigate the prevalence of recurrent genetic mutations in de novo MDS patients and elucidate the prognostic and predictive role of mutations on the 1st line decitabine treatment in MDS. Methods: We investigated genes including spliceosomal machinery genes (SRSF2, USAF1, ZRSR2) and methylating machinery genes (TET3 and DNMT2) and NRAS by Sanger sequencing in patients who were diagnosed with de novo MDS at Samsung medical Center between June 2008 and December 2011 and who were treated with 1stline 5-day regimen of decitabine treatment. Results: We analyzed clinical data including treatment outcomes in 70 patients (total 290 cycles). The overall response (complete remission, partial remission, marrow complete remission and hematologic improvement) rate was 52.5%. The median time to any response was two (range 1-6). Patients who showed hematologic improvements had significantly longer survival than those who did not (9.8 vs 22.9 months, P-value=0.004). The prevalence of mutations in the methylating machinery genes were 17.1% (N=12). In the baseline characteristic between wild type and mutated genes, there was no significant difference. The overall response rate was significantly higher in the patient who had the mutations in methylating machinery genes (46.6% vs 82.3%, P-value=0.027). Conclusions: The current results showed that methylating machinery gene TET2MUT, DNMT3AMUT had clinical relevance as preditive biomarker for hypomethylating agents.
FRI0151 Protein inhibitor of activated stat3 prevents peripheral arthritis and gut inflammation by regulating th17/treg cell imbalance via stat3 signalling in mice model of spondyloarthritis
Authors: E. Kwon, H.K. Min, M.Y. Kim, J. Choi, S.-Y. Lee, H.-B. Seo, K. Jung, H.S. Na, J.-G. Ryu, S.-K. Kwok, M.-L. Cho, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spondyloarthritis (SpA) is inflammatory arthritis, and interleukin (IL) −17 is crucial on pathogenesis of SpA. Type 17 helper T cell (Th17) is one of major IL-17 secreting cells. Signal transducer and activator of transcription (STAT)−3 signalling induces Th17 cell differentiation. Present study investigated the effect of protein inhibitor of activated STAT3 (PIAS3) on SpA pathogenesis. <h3>Methods</h3> Curdlan was injected to SKG ZAP-70<sup>W163C</sup> mice for SpA induction. Then PIAS3 or Mock vector was inserted to mice for 10 weeks. Clinical score and histologic scores of paw, spine, and gut were evaluated. Expressions of IL-17, tumour necrosis factor-α (TNF-α), STAT3, bone morphogenic protein (BMP) were measured. Confocal stain and flow cytometry were used to assess helper T cell differentiation. <h3>Results</h3> PIAS3 significantly diminished the histological scores of paw and gut. PIAS3 group displayed lesser expression of IL-17, TNF-α, and STAT3 in the paw, spine, and gut. BMP-2/4 expressions were lower in spine of PIAS3 group. Helper T cell differentiation was polarised toward upregulation of regulatory T cell (Treg) and downregulation of Th17 in the PIAS3 mice. <h3>Conclusions</h3> PIAS3 showed preventive effects in mice with SpA by suppressing peripheral arthritis and gut inflammation. Proinflammatory cytokines and Th17/Treg differentiation were controlled by PIAS3. Additionally BMPs were decreased in spine of PIAS3 mice. These findings suggest that PIAS3 could be a potential therapeutic choice of SpA treatment. <h3>References</h3> [1] Smith JA, Colbert RA: Review: The interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis &amp; rheumatology2014, 66:231–41. [2] O'Shea JJ, Lahesmaa R, Vahedi G, Laurence A, Kanno Y. Genomic views of STAT function in CD4+ T helper cell differentiation. Nature reviews Immunology2011;11:239–50. [3] Miossec P, Korn T, Kuchroo VK: Interleukin-17 and type 17 helper T cells. The New England journal of medicine2009;361:888–98. [4] Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, Brown MA, McGuckin MA, Thomas R. beta-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice. Arthritis and rheumatism2012;64:2211–22. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared
Health-Related Quality of Life Among Patients with Relapsed or Refractory Multiple Myeloma Who Received Pomalidomide, Bortezomib, and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone - Results from the Phase 3 Optimismm Study
Authors: Katja Weisel, Meletios A Dimopoulos, Philippe Moreau, Munci Yagci, Alessandra Larocca, Abraham S. Kanate, Filiz Vural, Nicola Cascavilla, Supratik Basu, Peter Johnson, Peter D. Byeff, Marek Hus, Paula Rodriguez Otero, Kosei Matsue, Ercan Muelduer, Pekka Anttila, Patrick Hayden, Maria-Theresa Krauth, Dina Ben-Yehuda, Larisa P. Mendeleeva, Shien Guo, Lea Purnomo, Xin Yu, Lara Grote, Tsvetan Biyukov, Mohamed Zaki, Paul Richardson
Journal: Blood (2018)
Gemcitabine versus cisplatin concomitant with radiotherapy for locally advanced squamous cell carcinoma of the head and neck.
Authors: Elsayed Mostafa Ali, Emad nabil Hassan, Ashraf Elyamany, Ahmed M Maklad, Ahmed Gaber Abdelraheem
Journal: Journal of Clinical Oncology (2014)

e17039 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with a global annual incidence of 500,000. HNSCC is a heterogeneous group of cancers, with a variable, prognosis .there is a need for different chemotherapeutic agent to be usead with radiation therapy to allow flexibility in patient treatment decision, for patient who my not tolerate platinum compound. our study was phase III study in which we compared low dose gemcitabine based chemoradiotherapy with cisplatin based chemoradiotherapy in regard to the response rate, survival and toxicity profilein locally advanced head and neck cancer Methods: Sixty patients with locally advanced head and neck cancer were included in this prospective comparative phase III randomized study, in the period from January 2011 to September 2013. The patients were treated in two randomized groups, each of them included 30 patients. Results: In gemcitabine arm (group A) 42.31% of the patients had stage III and 57.69% of them had stage IVa while 48.15% of the patients of cisplatin arm (group B) had stage III and 51.85% had stage IVa. The median duration of response in group A was 21 months, while in group B it was 23 months. The degree of response had a statistically significant effect on survival in group B patients. This was evident in patients who achieved partial response (PR) that showed lower survival than those with (CR). Conclusions: Gemcitabine has comparable radiosensitizer effect with acceptable toxicity profile and can be used as a radiosensitizer in head and neck cancers especially when cisplatin cannot be used and we recommend further studies to establish its rule.
Activation of the human natural killer cells NK-92 with a lymphocyte-derived cytokine-rich supernatant.
Authors: Ioannis F. Voutsas, Pinelopi Samara, Marinos Tsiatas, Margarita Skopeliti, Sotirios Fortis, Aristotelis Bamias, Sylvianna Georgaki, Ourania E. Tsitsilonis
Journal: Journal of Clinical Oncology (2014)

3108 Background: Ex vivo activated NK cells adoptively transferred to cancer patients were among the first lymphocyte populations used in immunotherapeutic protocols. To enhance NK cell cytotoxicity, individual cytokines, as well as cytokine combinations have been tested. In an effort to achieve optimal cytokine combinations, conditioned media collected upon stimulation of immune cells have also been assessed. Human lymphocytes activated in vitro with anti-CD3 mAb secrete various immunomodulatory agents in their culture supernatant (ACD3S). We tested the in vivo efficacy of ACD3S-activated NK-92 cells in an adoptive cell transfer cancer immunotherapeutic model in mice. Methods: ACD3S was collected by stimulating normal peripheral blood mononuclear cells for 3 days with immobilized anti-CD3. IL-2-depleted NK-92 cells were in vitro reactivated with ACD3S for 24 hours and their cytotoxic activity was determined using standard 51Cr-release assay against K562, FM-3 and MCF-7 targets. Perforin production was assessed by FACS. SCID mice subcutaneously inoculated with human tumor cells (FM-3 and MCF-7) were intraperitoneally administered 3 doses of ACD3S-activated NK-92 cells. Tumor growth and overall survival of the animals were recorded. Results: IL-2-depleted NK-92 cells showed reduced cytotoxicity againstK562, FM-3 and MCF-7 target cells. Brief exposure of NK-92 cells to ACD3S resulted in a statistically significant enhancement of their lytic ability against the same targets and their intracellular perforin production was restored to levels comparable to standard NK-92 cells. When ACD3S-activated NK-92 cells were administered to FM-3 or MCF-7 tumor-bearing SCID mice, a statistically significant delay in tumor growth was recorded. Moreover, adoptive transfer of ex vivo ACD3S-activated NK-92 cells was well tolerated and prolonged the survival of mice. Conclusions: We propose an alternative method for the in vitro enhancement of NK-92 cell cytotoxicity, which is retained after their adoptive transfer in animals. The protocol used for NK-92 cell activation is brief, of low cost and of low risk for side-effects, and thus could eventually be considered for the treatment of solid tumors.
Two-Year Evaluation of Mandatory Bundled Payments for Joint Replacement
Authors: Michael L. Barnett, Andrew Wilcock, J. Michael McWilliams, Arnold M. Epstein, Karen E. Joynt Maddox, E. John Orav, David C. Grabowski, Ateev Mehrotra
Journal: New England Journal of Medicine (2019)

In 2016, Medicare implemented Comprehensive Care for Joint Replacement (CJR), a national mandatory bundled-payment model for hip or knee replacement in randomly selected metropolitan statistical areas. Hospitals in such areas receive bonuses or pay penalties based on Medicare spending per hip- or knee-replacement episode (defined as the hospitalization plus 90 days after discharge).
Expression of c-Myc oncogene in sinonasal cancer.
Authors: Remon Bazak, Sumita Raha, Samy Elwany, Seddik Abdel Salam, Tatjana Paunesku, Gayle Woloschak
Journal: Journal of Clinical Oncology (2014)

e22176 Background: Most neoplastic cells need oncogenes for maintenance of the malignant phenotype and cell survival. Overexpression of c-Myc has been documented in both high-grade pre-malignancy and invasive tumors and has been associated with poor outcome. There is considerable evidence in the literature that inhibition of c-Myc expression in malignant cells results in inhibition of cell proliferation and induction of apoptosis. Despite its crucial role in cancer development and being a potential target for cancer therapy, expression of c-Myc has not been well documented in the nasal cancer cell line RPMI 2650. Methods: A modified FISH technique using Alizarin Red S coated nanoparticles conjugated to a DNA probe for c-Myc gene was used to detect the presence of c-Myc oncogene in RPMI 2650. The expression of c-Myc oncogene was tested in positive control HeLa cells and RPMI 2650 cell line with and without a challenge to induce c-Myc protein expression. The cells were challenged by exposure to 125 µM H2O2 for 3 hours and by serum starvation re-feeding (0.5% fetal bovine serum overnight incubation followed by 20% fetal bovine serum). A standard Western blot test was conducted to detect level of expression of c-Myc protein. Results: Modified FISH demonstrated the presence of c-Myc but no apparent gene amplification of c-Myc gene within the genome of RPMI 2650. The western blot showed a band around 62 kD which is the expected molecular weight of c-Myc confirming its expression by HeLa as well as RPMI 2650. c-Myc expression by the RPMI 2650 was stable and comparable to that in HeLa cells. Neither starvation re-feeding nor incubation with hydrogen peroxide increased the basal expression of c-Myc by the cells of RPMI 2650. Conclusions: c-Myc oncogene is expressed at a basal level in RPMI 2650 during cell replication. The activity of c-Myc thus appears to be required for development and maintenance of these cells, rendering c-Myc an emerging therapeutic target for managing cancer at the molecular level. Considering the ease of endoscopic access to sinonasal cancer and feasibility of direct delivery of a targeted agent, further research on c-Myc targeted therapy for sinonasal cancer is warranted.