bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation sequencing for genetic analysis of endobronchial ultrasound transbronchial needle aspiration samples in advanced lung cancer.
Authors: Min Xianjun , Li Mingwei , Liu Qiang , Yang Yingshun , Pei Guotian , Wang Shuai , Wang Xiaoyu , Wang Huina , Lou Feng , Cao Shanbo , Liu Jun , Huang Yuqing 
Published: May 2020

e15586 Background: Next-generation sequencing (NGS) typically requires greater quantities of DNA than traditional molecular testing. Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is a minimally invasive technique with high sensitivity in the mediastinal staging of lung cancer. This study aimed to evaluate the adequacy of EBUS-TBNA in providing adequate size specimens for genetic mutations and immunotherapy biomarkers analysis in patients with lung cancer. Methods: Tissue samples from patients with advanced lung cancer were collected by EBUS-TBNA and were formalin-fixed paraffin-embedded. NGS assay was carried on with acornmed panel including 808 genes. PD-L1 expression through immunohistochemistry was assessed. Results: A total of 98 patients was enrolled, of which 74 (76%) were adenocarcinoma and 20 (20%) were squamous cell carcinomas. Among the patients, 108 samples (including multipoint puncture of different location and retest of the same patient) were obtained. NGS assay was completed successfully on 106 of the 108 samples (98.14%), and 97.96% of patients had successful testing, identifying an average of 11.3 mutations. With a multi-gene panel comprising up to 808 tumor related genes, actionable variations were found in 93 (86%) samples. Of these, the positive rates of actionable alterations in lung adenocarcinoma samples and lung squamous cell carcinoma samples were 90% and 79%, respectively. The tumor mutation burden (TMB), Microsatellite instability (MSI) and PD-L1 expression were found High in 20 (41%), 1 (2%), and 37 (72%) patients respectively. Conclusions: NGS assay can be successfully conducted with tissue samples obtained from EBUS-TBNA. NGS assay provides more comprehensive information on genetic mutations in tumors, which greatly assists therapeutic decision making for advanced lung cancer.
The dark age of single organ screening is over: CD24 is a novel universal simple blood test for early detection of cancer.
Authors: Shapira Shiran , Kazanov Dina , Ben Shimon Marina , Hay Levy Mori , Mdah Fatin , Asido Shir , Carmel Narin , Yossepowitch Ofer , Grisaru Dan , Fliss Dan , Isakov Ofer , Lahat Guy , Nachmany Ido , Gluck Nathan , Peer Michael , Wolf Ido , Arber Nadir 
Published: May 2020

e15591 Background: More than 1.8 million new cancer cases are expected to be diagnosed in 2020. Only in the U.S, about 606,520 Americans are expected to die this year, which translates to about 1,660 deaths per day. However, when found early, in the asymptomatic phase, cancer is often effectively treated or even cured. The few cancer screens available today, including mammograms and colonoscopies, each look for a single type of cancer. CD24 is hardly expressed in normal cells (but to B-lymphocytes, differentiating neuroblasts and neutrophils) but is overexpressed in numerous human cancers. Aim: To establish a universal cancer screening blood test. Methods: Blood samples were obtained from consecutive patients and healthy volunteers. 1x106 leukocytes were stained using anti-CD11b-PerCp-Cy5.5 and anti-CD24-FITC and analyzed by flow cytometry (CyFlow Cube 6, Sysmex, Germany). Percentage of positive cells was determined by subtracting the percentage of CD24 and CD11b-positive cells (dual stain) from CD24-positive cells (single stain). The cut off for cancer detection was 25. Healthy subjects underwent a thorough evaluation at the health promotion center and integrated cancer prevention center. All cancers were verified histologically. Results: CD24/CD11b expression in the healthy population was evaluated in 337 women and 408 men, ages 20-85. There were 222 cancer patients. After excluding thyroid and bladder cancers, the assay detected 146 out of 196 (75%) cancers at all stages and even in 31 out of colonic adenomas (table). The levels of CD24 drop back to near normal level following successful surgery/chemotherapy. The test score was not affected by age, gender, fasting and the time of the day that the blood sample is taken. In 55 cases the test was performed twice, with similar results, as well as when the test was performed in another flow cytometry, after 1d, 1w, 1m after freezing . Conclusions: 1. CD24 is a universal cancer screening. 2. It can detect pre malignant lesions like adenomas in the colon. 3. Preliminary results suggest that it can serve as a predictive marker. [Table: see text]
Effect of UV-curable and injectable dendrimer matrix on tumor pharmacokinetics and survival in a hepatocellular carcinoma mouse model using interstitial photodynamic therapy.
Authors: Vuoti Sauli , Narasimha Kumar , Reinikainen Kai 
Published: May 2020

e15598 Background: Intratumoral drug delivery in cancer treatment has shown to increase drug accumulation in tumors and decrease adverse effects of systemic therapies. The active agent is typically required to stay in contact with the tumor and thus attachment directly into the tumor or to the surrounding tissue is warranted. In addition, a long-acting release of the active drug is vital. Dendrimers are nano-sized, radially symmetric molecules with homogeneous and monodisperse structures, which can used to encapsulate drug molecules for controlled release with the aid of external stimuli at physiological pH. Methods: We prepared a dendrimeric drug delivery matrix based on a PEG-core. The model drug (5-fluorouracil or doxorubicin) was covalently bonded to the core. The release of the drug was observed up to 29 days in vitro. The outer shell of the matrix was partially modified to obtain a fast UV-curing and subsequent attachment to the tumor tissue utilizing interstitial photodynamic therapy. We compared the pharmacokinetics, tissue distribution and antitumor efficacy of conventional systemic therapy and the intratumoral therapy in xenograft-bearing mice. In addition, we monitored blood parameters and body weight of the animals for adverse effects. Results: The dendrimer matrix caused significantly greater inhibition of human hepatocellular carcinoma xenograft tumor growth when compared with systemic therapy, without increasing toxicity. The matrix enabled a significant increase in drug accumulation in tumors, and markedly extended the survival of mice compared with systemic treatments. A larger decrease in blood parameters as well as spleen weight was observed in the systemic therapy group especially when using 5-fluorouracil. Conclusions: Our study shows that the intratumoral treatment strategy based on a novel UV-curable dendrimer hydrogel matrix enhances antitumor activity by improving pharmacokinetics and drug accumulation and increases efficacy in comparison to conventional systemic therapy. These results highlight the potential use of dendrimer hydrogels in the treatment of hepatocellular carcinoma.
LCN2 and colon cancer — Have we hit the jackpot.
Authors: Srinivasalu Vijay Kumar , Chaudhary Nazia , . Bhagyashree , Dwivedi Nehanjali , P K Smitha , Thorat Rahul , Batulla Christopher , Dhar Sujan Kumar , Dalal Sorab N , Das Manjula 
Published: May 2020

e15608 Background: Lipocalin2 (LCN2, also known as neutrophil gelatinase-associated lipocalin) is a protein that in humans is encoded by the LCN2 gene. Its abnormal expression serves critical roles in EMT transition, angiogenesis, cell migration and invasion in many cancers. We aim to assess the in vitro and in vivo effects of LCN2 as a potential chemo and radiosensitizer. Methods: Normalized RNAseq RSEM values of LCN2 were compared between normal and tumour samples from TCGA. Differences between median expression levels were assessed using Wilcoxon rank sum test. Kaplan-Meier model was used for survival analysis. Immune cell population in publicly available Colon Adenocarcinoma dataset was estimated using MCP Counter tool. Cell systems used to experimentally study the role of LCN2 in therapy resistance and tumor progression were HCT116, HT29 and DLD1. PKP3 and/or LCN2 were knocked down by shRNA. Tumor regression and therapy (5FU and radiation) sensitivity upon Anti-LCN2 treatment were demonstrated in Xenograft mouse models. Results: Analysis of 23 TCGA datasets containing gene expression data for both tumour and adjacent normal samples indicated that LCN2 levels are elevated in colon tumors. Colon cancer cell line HCT116 derived PKP3 knock-down or LCN2 over-expressing cells showed therapy resistance. A comparison of the tumor cell lines HCT116, HT29 and DLD1 show that increased LCN2 expression correlates with therapy resistance. LCN2 levels correlated with resistance to 5FU (p = 0.006) and its ability to clear ROS (p < 0.05) in vitro. Inhibiting LCN2 led to a decrease in invasion in vitro (p = 0.0005), increased sensitivity to 5FU in vitro (p = 0.001) and inhibition in tumor growth and increased sensitivity to 5FU and radiation (p = 0.005) in xenograft mouse models. On MCP counter analysis of TCGA, in Colon adenoca the normal samples show a correlation between LCN2 expression and T-cells (Pearson r = 0.45, p = 0.0028) and with the T-cell chemoattractant CXCL10 (Pearson r = 0.5, p < 0.0001). Such correlations are broken in tumour samples. Conclusions: LCN2 expression leads to chemo and radio resistance in colon cancer cell lines and xenograft mouse models. Inhibiting LCN2 function can inhibit tumor progression and sensitizes tumors to radiation and 5FU. These results suggest that LCN2 expression could be a marker that can be used to determine the choice of therapy offered to patients and that LCN2 could serve as a therapeutic target that sensitizes cells to radio and chemotherapy. LCN2 affects tumor progression and therapy sensitivity probably through T cell mediated immune pathway.
Prevalence of iron deficiency in cancer patients: The French prospective CARENFER study.
Authors: Luporsi Elisabeth , Carnot Aurelien , Massard Vincent , Morin Sophie , Chauffert Bruno , Turpin Anthony , Trochu Jean-Noël , Cacoub Patrice 
Published: May 2020

e15617 Background: Despite the potential deleterious consequences of iron deficiency (ID) in patients with cancer, under-diagnosis is frequent and existence of ID based on both serum ferritin concentration and transferrin coefficient saturation (TSAT) index is rarely determined. The CARENFER Study aimed to assess prospectively the prevalence of ID, anemia and iron deficiency anemia (IDA) in cancer patients. Methods: The study was conducted in France from May to July 2019, as a prospective cross-sectional survey carried out in 15 oncology units. The analysis focused on 1221 patients with different types of solid malignant tumors. Serum ferritin and iron concentrations, TSAT index and hemoglobin (Hb) level were determined. Based on ESMO 2018 Guidelines, ID was defined as ferritin < 100 μg/L or TSAT < 20%, and then categorized as either absolute ID (ferritin < 100 μg/L) or functional ID (ferritin ≥ 100μg/L and TSAT < 20%). Anemia was defined as Hb level ≤ 11 g/dL. Iron deficiency anemia (IDA) was defined according to ESMO 2018 Guidelines. The prevalence of ID, anemia and IDA was estimated using Agresti-Coull 95% confidence interval. Results: Patient’s median age was 63 years (55% women and 45% men). 89.4% of patients were currently under treatment for their cancer, mainly by chemotherapy (75.4%). The proportion of cancer patients with ferritin level < 100 μg/L was 20.5% [18.3-22.9] and 50.6% [47.8-53.4] of patients had a TSAT index < 20%. Overall, ID was found in 57.9% [55.1-60.6] of patients, with absolute ID accounting for 36% of all ID cases. 36.0% of patients were anemic and among them, IDA was reported in 21.8% [19.6-24.2] of patients. The type of cancer treatment did not influence the ID status as ID was also present in 57.4% of untreated cancer patient. Conclusions: This study highlights the high prevalence of ID in cancer patients, whether or not concomitantly associated with anemia or treatment. These results emphasize the need to better management of ID in cancer thereby optimizing overall patient care. Clinical trial information: NCT03924271.
Comparison of the tumor cells proliferative activity in donor tissue and samples of xenograft generations.
Authors: Lukbanova Ekaterina A. , Kolesnikov Evgeniy N. , Kozhushko Mikhail A , Kit Sergei , Myagkov Roman E. , Anisimov Aleksandr E. , Goncharova Anna S. , Protasova Tatiana P. , Karnaukhov Nikolay S. , Zaikina Ekaterina V. , Volkova A. V. , Mindar M. V. , Tkachev Sergey Yu. , Khodakova D. V. , Maksimov Aleksey Yu. , Vladimirova Liubov Yu 
Published: May 2020

e15619 Background: Esophageal cancer is a common tumor of the mucous layer of the esophagus and the sixth most common cause of cancer deaths worldwide. Studying the mechanisms of its occurrence and development and the search for new approaches to its prevention and treatment are relevant. Such studies require a reliable experimental basis with such an important component as the use of animal models of cancer. In vivo models are an important tool both for testing new drugs and for studying the mechanisms of disease development. The purpose of the study was to create a patient-derived xenograft (PDX) model of esophageal cancer and to evaluate the proliferative activity of cells in the donor tumor and in xenograft samples in a series of successive generations. Methods: A PDX model of esophageal cancer was created by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the distal esophagus of BALB/c Nude athymic mice. The tumor histotype was confirmed histologically (hematoxylin and eosin staining). The proliferative activity of cells was evaluated by immunohistochemistry (IHC) with anti-Ki-67 antibodies. Results: Histological identity of xenograft samples and the donor tumor was confirmed. IHC showed an increase in the proliferative activity index in samples of transplanted tumors compared to the donor material: 12.4% in the primary tumor and 58%, 65.2%, 54.2% and 60.7% in generations 1, 3, 4 and 5, respectively. Conclusions: Histological characteristics of the donor tumor are preserved in all PDX models. The study demonstrated an increase of the proliferative activity in the first PDX generation compared to the primary tumor which persisted in the subsequent models.
Bstronximab, a novel therapeutic antibody to treat metastatic testis cancer.
Authors: Schopperle William Michael 
Published: May 2020

e15621 Background: The treatment of metastatic testis cancer is by far the gold standard for treating metastatic solid cancers: over 90% of men diagnosis with metastatic testis cancer are completely cured with current therapies. What seems to be lost and somewhat surprising within this truly remarkable therapeutic cancer success in treating a metastatic cancer is the fact that in United States alone there are still over 400 young men who died from this disease because they do not respond to current therapies. Thus, despite the tremendous clinical success with treating this disease, there is still a strong unmet need to develop new treatments for men with metastatic testis cancer who fall outside the celebration of this disease as being completely cured. Methods: The human germ cell tumor embryonal carcinoma line, TERA-1. was used to generate purified testis cancer-specific cell membrane antigens to immunize mice and generated antibodies, by standard conventional mouse B cell hybridoma protocols. Isolated monoclonal antibodies where tested by ELISA and SDS-PAGE Western blotting to identify testis cancer specific antibodies. Testis cancer positive antibodies were further screen in an antibody-drug-conjugate screen to determine if the monoclonal antibody could function as a antibody-drug-conjugate therapeutic drug for metastatic testis cancer. Results: Dozens of monoclonal antibodies were generated with our antibody screen. Based on the screen results, a lead monoclonal antibody, named Bstrongomab, was selected for further development as a testis cancer therapeutic antibody. Bstrongomab is an IgG1 monoclonal antibody specific to the human embryonic cell marker, and testis cancer marker, TRA-1-60, a carbohydrate molecule which has been identified over 4 decades ago as a true human testis cancer marker. A human/mouse chimeric version of Bstrongomab was created - Bstrongximab - as a human therapeutic antibody. An antibody-drug-conjugate using Bstrongximab and the toxic payload MMAE (Monomethyl auristatin E) was developed and tested in pre-clinical human cancer testis in-vitro and in-vivo models and showed to be a powerful testis cancer therapeutic drug targeting TRA-1-60. Conclusions: Bstrongximab-MMAE is a novel therapeutic antibody-drug-conjugate which targets the testis cancer antigen TRA-1-60. TRA-1-60 is not expressed in normal tissues. Bstrongximab-MMAE is a new cancer drug ready to move into clinical trials for men with metastatic cancer that do not respond with current therapy protocols.
Multi-analyte interrogation based treatment of advanced refractory cancers.
Authors: Akolkar Dadasaheb B , Crook Timothy , Patil Darshana , Ranade Anantbhushan , Bhatt Amit , Limaye Sewanti , Datta Vineet , Schuster Stefan , Sims Cynthe , Srivastava Navin , Fulmali Pradip , Fulmali Pooja , Devhare Pradip , Patil Sanket , Apurwa Sachin , Srinivasan Ajay , Datar Rajan 
Published: May 2020

e15624 Background: Treatment of advanced refractory cancers face challenges in non-availability of systemic therapy regimens with evidenced benefit. Post failure of two to three lines of systemic treatments, patients with such cancers are usually considered for palliation or clinical trials. Prior attempts at label-agnostic treatment regimens (precision medicine) in such populations were largely based on a single-indication-single-drug paradigm which had limited application. We hypothesized that advanced refractory malignancies have latent vulnerabilities which can be identified by an integrational multi-analyte interrogation of the tumor, and can be targeted using patient-specific combination regimens to yield clinical benefit. Methods: Fresh tumor tissue and blood samples were obtained from 158 patients with solid organ cancers where the disease had progressed following failure of at least two lines of standard of care systemic treatment options. These samples were used for Encyclopedic Tumor Analysis (ETA) which interrogated gene mutations, gene overexpression, pathway dysregulation, immunohistochemistry as well as in vitro chemosensitivity profiling of viable tumor cells. Integration of datasets from the multi-analyte ETA was used to generate patient-specific therapy recommendations. Patients who received ETA-guided treatments were followed up and response to treatment was retrospectively evaluated from radiological scans. Results: All patients received ETA-guided individualized treatments which were combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Complete or Partial Response (CR or PR) was observed in 76 patients yielding an Objective Response Rate (ORR) of 48.1%. 67 patients showed Stable Disease (SD), thus yielding a Disease Control Rate (DCR) of 90.5%. Median Progression Free Survival (PFS) was 117 days (Range 27 – 379 days). There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: Viable efficacious combination treatment options can be made available for patients with advanced refractory malignancies via ETA, despite perceived non-availability or non-viability of standard of care treatment options.
Biosimilar trastuzumab active post-marketing surveillance real-world data update: Results from a patient support program for patients under treatment with the first biosimilar trastuzumab approved in Brazil.
Authors: Silva Allisson Monteiro da , Paulo Jaqueline Amália de , Watanabe Thais Tiemi , Dib Gislaine Villarta Capeleti 
Published: May 2020

e15626 Background: In 2017, biosimilar trastuzumab (Zedora) became the first biosimilar trastuzumab approved in Brazil. In 2019, biosimilar trastuzumab early data from an active postmarketing surveillance program were presented in ASCO. Now, with an extended follow up and more patients included, we present updated data from the surveillance program. Methods: This is a prospective observational study based on a patient support program. HER2 + breast cancer (BC) who received prescription for biosimilar trastuzumab were invited to participate. After agreement of informed consent, they were followed by periodical phone calls after each infusion and up to 3 months after the end of treatment. Treatment related data and adverse events (AEs) were collected. Results: A total of 76 female patients with HER2 + BC were enrolled in the program between May 2018 and December 2019. 74 patients with median age 51 (range 30 to 80) received at least one biosimilar trastuzumab infusion. Out of these, 52 (70.3%) patients reported 385 AEs all-causality (Table 1). Regarding severity and expectedness, 344 (89.4%) were non-serious AE (243 expected / 101 unexpected) and 41 (10.6%) were serious AE (29 expected / 12 unexpected). Considering all serious unexpected AEs (12), 8 were assessed as unlikely and 4 as likely. For the non-serious unexpected AEs (101) causality assessment was unlikely in 32 AEs, likely in 68 AEs and conditional in 1 AE. The three most frequently reported AEs according to SOC (System Organ Classification) were gastrointestinal disorders 59 (15.3%), general disorders and administration site conditions 57 (14.8%). The five most reported symptoms (PT - Preferential Term) were nausea 15 (3.9%), fatigue 14 (3.6%), infusion reactions 14 (3.6%), diarrhea 9 (2.3%) and insomnia 9 (2.3%). Further monitoring is continued. Conclusions: Nature of AEs for biosimilar trastuzumab are consistent with the label in female patients with HER2 + BC. The risk benefit remains consistent with the label and no new safety signals were detected. [Table: see text]
Injection mixed drug intratumoral to produce ROS and creating a coagulum as cancer therapeutics drug depot.
Authors: Zhang Jian , Fu Qiang , Li Bian , Han Yan , Chen Dong , Zheng Guoqin , Zhao Ming , Yu Baofa 
Published: May 2020

e15635 Background: To explore the nature of hydrogen peroxide at higher dosage for denature-aggregation of tumor with drugs through aggregation in denatured tumor as a coagulum for drug depot and prolong function of drug. Methods: (1). Preparation for two 5 ml of BLM-I131, one diluted with 0.12 ml NS and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in control group; one diluted with 0.12 ml of H2O2 (0.833 mg/ml) and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in experimental group. (2).Tumor imaging with BLM-I131 analyzed at different time points. (3). Radioactivity in tumor of mice analyzed under SPECT scanning imaging instrument at the 0, 5 h, 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 96 h, 120 h, 144 h and 168 h, activity of isotope I131 is representing the BLM retaining time in tumor. (4). Also, tumor sectioned and observed cellular and extracellular matrix changes of histological structure. Results: It was observed that BLM-I131 with ROS in tumors sustained for 168 hours while BLM-I131 with NS in tumors sustained for 8 hours only. Radioactivity of BLM-I131 in tumors with ROS reach at peak 1.5 hours and second peak at 20 hours by average to extend to 168 hours, while radioactivity of BLM-I131 in tumors with NS reached at peak in 0.5 hour, decreased to 30% in 1.5 hour quickly to background in 8 hours; We observed the extracellular matrix changes in experimental tumor while no changes in control tumor. Conclusions: A water soluble oxidant mixed with free drug can play a biological scissors role to chop tumor matrix, then it resulted in a denature tumor matrix into a coagulation for a drug depot, it showed drug of BLM-I131 sustained in tumor for a long time; while oxidant plays an important role to punch holes on cell membrane and resulted a high permeability for high concentration drug in each cancer cells.