tbuckley/cabot-search huggingface dataset:
The role of parents awareness to decision on HPV vaccination in Kazakhstan.
Authors: Dilyara Kaidarova, Nadejda Nasrytdinova, Murat Kairbayev
Journal: Journal of Clinical Oncology (2017)

e17008 Background: Despite the proven effectiveness of HPV vaccination against cancer and precancerous lesions the acceptance rates are not perfect. The goal of the study was to look how parents awareness about HPV affected decision to vaccinate their daughters. Methods: The interview was held in schools where first HPV vaccination trial program started. The survey included questions about social and economic status, HPV and HPV vaccine awareness, the source of information on HPV and decision about vaccination. The number of surveyed parents was 357. Correlation statistics and chi-square test have been used with SPSS 19 (IBM corp.). Results: 34.7±2.52% though that HPV vaccine can protect from other STI. There was significant dependability from the country region (p=0.001) and type of urban area (p=0.017). 136 respondents out of 357 agreed to vaccinate their daughters (38.1%±2.6%). The decision to vaccinate depends from age (p=0.006), sex (p= ≤0.001) and family history of cancer (р=0.001). As the main source of information about HPV vaccine parents highlighted gynaecologists (54.0±3.02%), and paediatricians (22.8±2.54%). Most belief that vaccine protects from cancer 65.4±2.46%, whereas 16.8±1.98% trust their medical caregivers. The answers of parents depends from country region (р≤0.001), urban area (р≤0.001), sex (р=0.004), education (р=0.001), religion (р≤0.001) and family history (р≤0.001). Conclusions: The acceptance rate of HPV vaccine in trial is very low, most have doubts regarding the importance of vaccinations. There is a significant room for improvement, HPV and HPV vaccination awareness programs are needed to increase the acceptance rate of the vaccine in Kazakhstan.
Lenvatinib in combination with everolimus in metastatic renal cell carcinoma (mRCC) resistant to antiangiogenic targeted therapy: An initial Russian experience.
Authors: Maria Volkova, Olga Igorevna Samuseva, Anna Sergeevna Olshanskaya, Vsevolod B. Matveev
Journal: Journal of Clinical Oncology (2018)

e16562 Background: : A preliminary assessment of safety, tolerability, and efficacy of lenvatinib in combination with everolimus in unselected patients (pts) with mRCC resistant to antiangiogenic targeted therapy. Methods: We analyzed the medical data of 19 consecutive mRCC pts who received lenvatinib (18 mg QD) in combination with everolimus (5 mg QD) following at least one antiangiogenic targeted therapy failure. Median age was 55 (23-73) years. ECOG PS 0-1 was in 11 (57.9%), ECOG 2-4 – in 8 (42.1%) cases. Four (21.1%) patients were distributed into the good, 10 (52.6%) – into the intermediate, and 5 (26.3%) – into the poor IMDC prognostic group. Multiple mts were diagnosed in 18 (94.7%), multiple mts sites – in 17 (89.5%), liver mts – in 6 (37.6%) cases. All pts were previously treated with anti-angiogenic targeted agents and received 1-4 lines of therapy (≥2 – 12 (63.1%)). Median follow-up was 5 (2-10) months. Results: By the time of the analysis, 12 (63.2%) pts were treated, 7 (36.8%) – discontinued combined treatment (due to RCC progression - 4 (21.1%), toxicity - 2 (10.5%), death from unrelated reason – 1 (5.3%)). Mean treatment time was 5.1 (1.9-11.2) months. Adverse events (AE) occurred in 17 (89.5%) pts (grade 3 - 3 (15.8%), grade 4 – 0 (0.0%), grade 5 - 1 (5.3%)). The most common AE were diarrhea (68.4%), stomatitis (57.9%), hypertension (42.1%), and weight loss (47.4%). Lenvatinib or everolimus dose was reduced in 5 (26.3%) and 0 (0.0%) pts and interrupted in 5 (26.3%) and 1 (5.3%) pts, respectively. Partial Response occurred in 1 (5.3%) patient and Stable Disease in 18 (94.7%) cases. Tumor shrinkage was occurred in 12 (63.2%) (median – 17% (3-40%)), stabilization in 8 (42.1%), enlargement in 1 (5.3%) patient. Median time to maximal response was 2 (2-4) months. Five-months progression-free survival rate was 87.4%. Following 2 cycles of combined therapy ECOG PS improved in 11 (57.9%), stabilized in 6 (31.6%), worsened in 2 (10.5%) pts. Conclusions: Our preliminary data have demonstrated antitumor activity and acceptable tolerability of lenvatinib in combination with everolimus in unselected pts with mRCC resistant to antiangiogenic targeted therapy.
Histone deacetylase 6 in cancer
Authors: Ting Li, Chao Zhang, Shafat Hassan, Xinyue Liu, Fengju Song, Kexin Chen, Wei Zhang, Jilong Yang
Journal: Journal of Hematology & Oncology (2018)

Histone acetylation and deacetylation are important epigenetic mechanisms that regulate gene expression and transcription. Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family that not only participates in histone acetylation and deacetylation but also targets several nonhistone substrates, such as α-tubulin, cortactin, and heat shock protein 90 (HSP90), to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. Furthermore, HDAC6 also upregulates several critical factors in the immune system, such as program death receptor-1 (PD-1) and program death receptor ligand-1 (PD-L1) receptor, which are the main targets for cancer immunotherapy. Several selective HDAC6 inhibitors are currently in clinical trials for cancer treatment and bring hope for patients with malignant tumors. A fuller understanding of HDAC6 as a critical regulator of many cellular pathways will help further the development of targeted anti-HDAC6 therapies. Here, we review the unique features of HDAC6 and its role in cancer, which make HDAC6 an appealing drug target.
Abstract 15453: CD34+ Cell Therapy May Affect Extracellular Matrix Turnover in Patients With Non-ischemic Dilated Cardiomyopathy
Authors: Jus Ksela, Gregor Poglajen, Elizabeta Boznar Alic, Milan Skitek, Matjaz Sever, Ivan Knezevic, Francois Haddad, Joseph C Wu, Bojan Vrtovec
Journal: Circulation (2015)

Introduction: The underlying mechanisms of CD34+ cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM) remain poorly defined Hypothesis: We sought to evaluate the effects of CD34+ cell therapy on extracellular matrix. Methods: We performed a cohort analysis of 23 consecutive patients with DCM who underwent transendocardial CD34+ cell transplantation between January and December 2013. All patients received 5-day stimulation with G-CSF; CD34+ cells were selected with apheresis and injected transendocardially guided by electroantomical mapping. Patients were followed for 6 months and good clinical response was defined as an increase of left ventricular ejection fraction (LVEF) ≥5%. Extracellular matrix turnover was evaluated by measuring changes in galectin-3 serum levels. Results: Within 6 months after cell therapy galectin-3 levels decreased in 9 (39%) patients (Group A) and increased in 14 (61%, Group B). The two groups did not differ with regards to gender (male: 100% in Group A vs. 78% in Group B; P=0.15), age (51±10 years vs. 52±11 years; P=0.79), serum creatinine (86±22 μmol/L vs. 82±17 μmol/L, P=0.62), bilirubine (20±11 μmol/L vs. 17±9 μmol/L, P=0.51), or NT-proBNP levels (1465±1448 pg/mL vs. 1380±1626 pg/mL, P=0.72). Baseline LVEF (28±9% vs. 33±7%, P=0.10) and left ventricular end-diastolic diameter (7.1±0.8 cm vs. 6.5±0.7 cm, P=0.22) were also comparable in the two groups. Both groups received comparable doses of CD34+ cells (84±51 million cells in Group A vs. 132±96 million cells in Group B, P=0.21). At 6 months LVEF increased significantly more in Group A than in Group B (9.2±5.1% vs. 3.4±5.2%, P=0.01) and the same was true for 6-minute walk test distance (83±47 m vs. 37±27 m, P=0.03). NT-proBNP decreased in Group A (-356±684 pg/mL), but not in Group B (+449±1040 pg/mL, P=0.07) and overall clinical response was significantly better in Group A than in Group B (responders: 88% vs. 33%, P=0.008). Conclusions: In non-ischemic DCM, clinical response to CD34+ cell therapy appears to correlate with changes in galectin-3 serum levels. This suggests that the effects of CD34+ cell therapy may be partially mediated through remodelling of the extracellular matrix.
Metronomic therapy versus best supportive care in progressive pediatric solid malignancies: A double blind placebo controlled randomized study.
Authors: Raja Pramanik, Sameer Bakhshi, Sandeep Agarwala, Yogendra Kumar Gupta, Sanjay Thulkar, Sreenivas Vishnubhatla, Atul Batra, Deepa Dhawan
Journal: Journal of Clinical Oncology (2016)

10520 Background: Although oral metronomic chemotherapy is often used in progressive paediatric solid malignancies in the palliative setting, its usage is notable for scepticism and empiricism.Literature review shows only single arm retrospective or phase I/II studies. Methods: We designed a phase III, double blinded, placebo controlled randomised study in primary extracranial, non- haematopoietic, paediatric solid malignancies who had progressed after at least 2 lines of chemotherapy with no further curative options. It was a parallel design superiority study. One group received best supportive care and placebo while the other received best supportive care along with a 4 drug antiangiogenic chemotherapy regimen of thalidomide, celecoxib, and alternating cycles of etoposide and cyclophosphamide. Included patients were aged 5-18 years, had ECOG PS ≤ 3(at least ambulatory with crutches or wheel chair), normal LFT and RFT, platelets > 75,000/mm3 and ANC>1000/mm3. Patients unable to swallow capsules were excluded. Disease status was assessed at baseline, at 9 weeks (or earlier if progressed), at 18 weeks (or earlier if progressed) and at 27 weeks using RECIST 1.1. The primary end point was progression free survival (PFS). Secondary endpoint was overall survival (OS). Results: From Oct 2013 to Dec 2015, we screened 123 patients and after informed consent enrolled 108 patients. 52 were randomised to placebo group and 56 to metronomic group. At a median follow up of 4 months, the PFS in the placebo arm was 46 days (95% CI= 33-58) while it was 49 days (95% CI= 43-59) in the metronomic arm, p=0.07. The median OS was also not significantly different [placebo=85 (95%CI=61-123) days vs metronomic= 85 (95%CI=69-113) days], p= 0.21. In a post-hoc subgroup analysis, the cohort receiving > 3cycles [HR (PFS) =0.47 (95% CI=0.24-0.94), p=0.03] and those without a bone-sarcoma (PNET or Osteosarcoma) [HR (PFS)=0.39 (95% CI=0.18-0.81),p=0.01] appeared to benefit from metronomic therapy. Conclusions: In this first prospective randomised study in pediatric metronomics, metronomic chemotherapy did not improve PFS or OS in progressive solid paediatric malignancies as compared to placebo. Clinical trial information: NCT01858571.
CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets
Authors: Ana R. Cortazar, Veronica Torrano, Natalia Martín-Martín, Alfredo Caro-Maldonado, Laura Camacho, Ivana Hermanova, Elizabeth Guruceaga, Luis F. Lorenzo-Martín, Ruben Caloto, Roger R. Gomis, Iñigo Apaolaza, Victor Quesada, Jan Trka, Antonio Gomez-Muñoz, Silvestre Vincent, Xose R. Bustelo, Francisco J. Planes, Ana M. Aransay, Arkaitz Carracedo
Journal: Cancer Research (2018)

With the advent of OMICs technologies, both individual research groups and consortia have spear-headed the characterization of human samples of multiple pathophysiologic origins, resulting in thousands of archived genomes and transcriptomes. Although a variety of web tools are now available to extract information from OMICs data, their utility has been limited by the capacity of nonbioinformatician researchers to exploit the information. To address this problem, we have developed CANCERTOOL, a web-based interface that aims to overcome the major limitations of public transcriptomics dataset analysis for highly prevalent types of cancer (breast, prostate, lung, and colorectal). CANCERTOOL provides rapid and comprehensive visualization of gene expression data for the gene(s) of interest in well-annotated cancer datasets. This visualization is accompanied by generation of reports customized to the interest of the researcher (e.g., editable figures, detailed statistical analyses, and access to raw data for reanalysis). It also carries out gene-to-gene correlations in multiple datasets at the same time or using preset patient groups. Finally, this new tool solves the time-consuming task of performing functional enrichment analysis with gene sets of interest using up to 11 different databases at the same time. Collectively, CANCERTOOL represents a simple and freely accessible interface to interrogate well-annotated datasets and obtain publishable representations that can contribute to refinement and guidance of cancer-related investigations at all levels of hypotheses and design.Significance: In order to facilitate access of research groups without bioinformatics support to public transcriptomics data, we have developed a free online tool with an easy-to-use interface that allows researchers to obtain quality information in a readily publishable format. Cancer Res; 78(21); 6320-8. ©2018 AACR.
TCT-732 Readmission and Mortality in Patients Undergoing Percutaneous Coronary Intervention Stratified by Access Site: Adjusted and Propensity Score Matched Analyses
Authors: Ahmad Masri, Michael Sharbaugh, Andrew Althouse, Amanda Malecky, Floyd Thoma, Catalin Toma, Mourad Senussi, Anson Smith, John Schindler, Joon Lee, Suresh Mulukutla
Journal: Journal of the American College of Cardiology (2018)
CYP2D6 polymorphism in Chinese breast cancer population.
Authors: Kai Li, Ning Liao
Journal: Journal of Clinical Oncology (2018)

e13529 Background: This study was carried out to estimate the allele and genotype frequencies of common variants in the CYP2D6 in Chinese population. Methods: We evaluated the CYP2D6 polymorphism of 448 Chinese breast cancer patients. Genomic DNA was extracted from peripheral blood or breast cancer tissue and genotyped for CYP2D6*10 by NGS. SNP genotyping were conducted via NGS (next-generation sequencing). Results: The allele frequence of CYP2D6*10 in the Chinese population is 59.4%. And this CYP2D6*10 allele frequence when detected from breast cancer tissue and blood, which was 59.9% and 57.1% respectively, was found to have no significant difference. The genotye frequencies of CYP2D6*10 were 39.8%, 30.0%, 30.3%, for wild-type, heterozygous and homozygous type respectively. We also found this SNP had no significant correlation with clinical characteristics. Conclusions: The results showed that the CYP2D6*10 allele frequence is high and about 59.4% in Chinese population. And there is no significant difference between blood and breast cancer tissues. And no difference is found when it is carried out by NGS comparing to those by polymerase chain reaction-restriction fragment length polymorphism analysis.
Abstract 13542: Psychosocial Predictors of Duration of Obesity: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Rebecca Cooper-McCann, Jared Reis, Catherine Loria, Cora E Lewis, Colby Ayers, Ana Diez-Roux, Tiffany M Powell-Wiley
Journal: Circulation (2015)

Introduction: Cumulative exposure to excess adiposity contributes significantly to cardiovascular morbidity and mortality. However, little is known about associations of psychosocial factors [life events (LE) and social support (SS)] with duration of abdominal obesity (DOB). Methods: Baseline data were collected in CARDIA from 1985-1986 (N=5115). Participants completed an 11-item SS scale, from Seeman’s and Syme’s work (higher score=higher support), and a 66-item LE scale, from the Psychiatric Epidemiology Rating Interview (higher score=more stressful events exposure in prior year). Associations between baseline SS and LE and DOB were investigated using multivariable linear regression. Abdominal obesity was waist circumference (WC)&gt;102cm for men and &gt;88cm for women. DOB was defined as cumulative abdominal obesity years based on measured WC every 3-5 years in the 25-year study. Results: Among 4214 participants not initially obese, DOB ranged from 0-25 years with a median of 10 years/person. At baseline, those with high LE scores were younger, more likely to be black, with less education, greater total physical activity (PA), greater energy intake (EI) and current/past smoking, while those with high SS score were more likely to be female, black, with higher education, higher PA, lower EI and smoking. In stratified linear regression models adjusted for covariates, each 1-unit higher LE score was associated with longer DOB for white women (Table). In contrast, a 1-unit higher SS score was associated with shorter DOB for white women and white men. No associations were observed among black men or women. Conclusions: Psychosocial factors were associated with duration of abdominal obesity, with a positive association between LE score and DOB for white women, and an inverse association between SS score and DOB for white women and men. These factors may identify those most at risk for greater cumulative exposure to adiposity and may serve as obesity prevention targets.
Construction of a control database for the filtering of germline mutations and false positive mutations in the detection of tumor somatic variations.
Authors: Yuhang Cai, Chunli Wang, Xinying Wang, Pei Meng, Mao Mao, Mingzhi Ye
Journal: Journal of Clinical Oncology (2018)

e24188 Background: With the development of the next-generation sequencing, the tumor mutation detection is more extensive. Generally, it uses non-tumor tissue to distinguish somatic and germline mutations. The non-pathogenic and false positive variations may increase the clinical consultation difficult and psychological burden of patients. Developing a method for germline distinguish, filter of non-pathogenic and false positive mutations can be clinically valuable. Methods: We construct a highly population frequency SNP database(HPF-SNP) based on 7425 tumor data of BGI’s Oseq-T (a tumor genetic testing product with 636 genes), to ensure that only highly reliable somatic mutations are retained. First, analysis 7425 samples data by QC method consisted of low depth, GC abnormalities, Q30 unqualified and etc. Then the samples detected SNV candidate mutations. Finally, the frequency distribution of the candidate SNV loci was calculated. HPF-SNP consists of two parts, Germ_Control_Set is for filter germline mutation and Low_Freq_Set is for filter positive mutations. 743 samples were used for the consistency validation. Results: HPF-SNP containing total 178195 SNP loci with a frequency range from 0.001 to 1. 743 samples were analyzed by two pipelines: I. Paired-calling pipeline which requires tumor samples and matched normal controls. II. Single-calling pipeline which requires only tumor samples and HPF-SNP. After filtered, 94.51%(237072/250821) of specific mutations called by single-calling pipeline can be filtered out, means HPF-SNP has the potential of filtering germline mutations. It also found that paired-calling pipeline mutations filtered by HPF-SNP, 98.81%(36756/37197) was false positive mutations. Conclusions: HPF-SNP is effective, nearly 95% of additional mutations can be filtered out. HPF-SNP makes the somatic mutation detection is no longer limited to paired control samples. HPF-SNP database can be used to analyze somatic mutations in tumor samples without control sample. Taking into the convenience of clinical sampling and the simplification of the detection process, HPF-SNP database has an extensive and effective clinical application.
Phase II, noncomparative, open label, multicenter, study of osimertinib, in patients with locally advanced or metastatic EGFR mutated, T790M undetectable or unknown non-small cell lung cancer (Stage IIIB-IV) after no immediate prior EGFR TKI (OSIRIS study).
Authors: Hector J. Soto Parra, Laura Noto, Francesco Verderame, Domenico Galetta, Vito Barbieri, Francesco Ferrau, Maria Rita Migliorino, Annamaria Catino, Marco M. Aiello, Enrica Capelletto, Serena Ricciardi, Francesca Spinnato, Pierfrancesco Tassone, Anna Maria Morelli, Fiorenza Latteri, Lucia Gozzo, Oriana Valerio, Rossana Avola, Silvia Novello
Journal: Journal of Clinical Oncology (2021)

e21116 Background: Osimertinib (OSI) is a potent irreversible EGFR TKI approved for 1st line therapy advanced EGFR+ NSCLC and for 2nd line T790M+ pts. The AURA trial showed promising results even in pts with T790M- NSCLC after no immediate prior OSI in locally advanced or metastatic EGFR+ NSCLC, T790M undetectable or unknown, after 1st line EGFR TKI and subsequent chemotherapy. Methods: This phase II trial was performed to investigate the role OSI in locally advanced or metastatic EGFR+ NSCLC, T790M undetectable or unknown, after 1st line EGFR TKI (1 or 2 generation) and subsequent chemotherapy. Eligible pts (M or F, &gt; 18 years, ECOG 0-2) received OSI (80 mg/day) until disease progression or unacceptable toxicity. Objective response rate (ORR) was the primary endopoint. Assuming a 10% attrition rate, 90 pts were planned to be enrolled according to the Optimal Simon’s 2 stage design. In the first stage, 32 pts were planned to be accrued, and if ≤ 3 responses were observed the study would be stopped. Otherwise, 49 additional pts were planned to be accrued. The null hypothesis would have been rejected if ≥ 12 responses were observed. This design yields a type I error rate of 0.05 and 80% power. Results: From May 2017 to October 2020, a total of 54 pts were enrolled (17 M and 37 F, mean age 66 years). The study was stopped early due to an extremely slow enrolment rate. However, the ORR of 31.5% (95% CI 19.5% - 45.5%) was significantly higher than the null hypothesis of 9% (p&lt;0.0001). 17 pts obtained a partial response and 20 a stable disease with an overall disease control rate of 68.5%. Median PFS was 9 mos and median OS was 15 mos. Forty-one pts experienced at least 1 adverse event (51.8% treatment related), more than 90% Grade 1 or 2, the most common being diarrhea. Conclusions: Despite early termination and incomplete recruitment, the treatment with OSI in pts with undetectable or unknown T790M showed a significant ORR and a PFS in line with results in T790M+. Currently, OSI represents the preferred option in naïve pts with EGFR+ NSCLC, regardless of T790M status and for pts who progress the recommended subsequent therapies include local therapy, continuing OSI or chemotherapy; in this new scenario, our results confirm that OSI rechallenge in subsequent line after chemotherapy should be explored. This research was conducted with support from AstraZeneca. Clinical trial information: 2016-002555-17.