bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chemoattractant chemerin as a natural tumor suppressive cytokine.
Authors: Pachynski Russell Kent , Zabel Brian , Tejeda Nicole , Monnier Justin , Holzer Alison K , Gentles Andrew , Kohrt Holbrook Edwin , Hadeiba Husein , Alizadeh Arash A. , Butcher Eugene 
Published: March 2020

e21071 Background: Infiltration of specialized immune cells regulates the growth and survival of neoplasia. In a survey of public whole genome expression datasets we found that the gene for chemerin, a widely expressed endogenous chemoattractant protein, is downregulated in melanoma as well as other human cancers. Moreover, high chemerin mRNA expression predicted improved outcomes in human melanoma. Methods: Forced re-expression of chemerin by tumor cells was achieved by transfection. An alternate strategy involved direct intratumoral injection of recombinant chemerin into tumors. Tumor line expression of chemerin was confirmed by ELISA and functionality of expressed, secreted chemerin confirmed by chemotaxis of CMKLR1 (the main receptor for chemerin) positive cells. Tumors were evaluated by FACS and immunofluorescence for presence of recruited leukocytes. Results: In studies of the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Growth inhibition was associated with an altered profile of tumor infiltrating cells with an increase in natural killers (NK cells), and a relative reduction in myeloid derived suppressor cells and putative immune inhibitory plasmacytoid DC. Tumor inhibition required host expression of CMKLR1, the chemoattractant receptor for chemerin, and was abrogated by NK cell depletion. Intratumoral injection of chemerin also inhibited tumors, suggesting the potential for therapeutic application. Conclusions: We therefore conclude that chemerin recruits anti-tumor immune effector cells, and that it may act as an endogenous tumor suppressor, whose downregulation in melanoma and potentially other neoplasia contributes to immune evasion and tumor growth.
Triple probe FISH approach for detecting EML4-ALK gene rearrangement in Chinese patients with NSCLC.
Authors: Mao Weimin , Han Mark , Ling Zhiqiang , Sun Wenyong , Zhang Gu , Dong Hongshan , Zhang Yingzi 
Published: March 2020

e21080 Background: The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target for the therapy of a subset of non-small cell lung cancer (NSCLC). ALK rearrangement has been found in approximately 1.6–11.6% of NSCLC in unselected patient populations, but the frequency also varied when different diagnostic approach was used. We, for the first time, investigated frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC using recent developed fluorescence in situ hybridization (FISH) triple color break-apart probe. Methods: One hundred-thirty one FFPE specimens from NSCLC patients were collected for the investigation. Fusion between 3’ portion of ALK gene and the 5’ portion of EML4 gene was detected using FISH tri-check probe (ZytoVision, Germany). Positive cells were defined as having any signal A ( distance more than two-time the ALK signal size) or signal B ( distance between one- and two-time the ALK signal size plus EML4 translocation signal) or any isolated ALK 3’ signal. Total 100 nuclei for each specimen were counted. Specimen was as classified as EML4-ALK rearrangement when the proportion of positive cells was over 15%. ALK/EML4 signals over 6 in over 10% nuclei were classified as gene amplification. Results: Of 131 specimens, frequency of ALK rearrangement was 10.7% (14/131) when positive cells were counted by signal A and isolated ALK 3’ signal (dual color). Frequency of EML4-ALK rearrangement was 13.0% (17/131) when positive cells were counted by signal A, B and isolated ALK 3’ signal (triple color), in which 21% (17/14) more cases were classified as EML4-ALK rearrangement comparing dual color enumeration. ALK and EML4 amplification were observed in 2.3% (3/131) specimens, respectively, in which two were co-amplified and none of them had EML4-ALK rearrangement. Conclusions: Present result showed that frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC was 13.0% determined by FISH tri-check probe. This study suggested that counting both ALK inversion and EML4 translocation may contribute to defining EML4-ALK positive cells.
Local infiltration of lymphocytes in large bowel tissue cancer and chronic colitis.
Authors: Nikipelova Elena A , Kit Oleg I 
Published: March 2020

e21101 Background: comparative analysis of concentrations of lymphocyte subpopulations in tissue of various intestinal zones in cancer of large bowel and chronic atrophic colitis. Methods: subpopulation composition of T- (CD3, CD4, CD8) and B- (CD19) lymphocytes, natural killers NK (CD16CD56), and T-lymphocytes with antigen-recognizing receptors TCRαβ and TCRγδ were examined in bowel adenocarcinoma tissue, peritumoural zone (1-3 cm away from tumour) and in resection line (10 cm away from tumour edge) and in chronic colitis tissue. Flow cytofluorimetry was used for immunophenotyping of the lymphocytes Results: 52 cases of adenocarcinoma and 24 cases of chronic colitis were examined. CD3 level in tumour tissue (64.2±3.6%) didn’t differ from this in colitis samples (65.6±3.5%); CD3 level was significantly lower in peritumoural zone and resection line (54.9±4.0% and 51.9±3.6%, correspondingly, p<0.05) than in colitis samples. The quantaty of lymphocytes with TCRαβ receptor in all tissue samples with cancer was significantly higher in comparison with one in chronic colitis samples. The level of lymphocytes with TCRαβ receptor in all tissue samples with cancer was 49.8±7.25, in peritumoural zone – 39.3±5.9%, in resection line 46.5±6.0%, compared to chronic colitis – 20.7±5.7%, p<0.05. Concentration of lymphocytes with TCRγδ receptor in cancer samples was 3-5 times less (tumour – 14.2±4.8%, peritumoural zone – 9.5±1.5%, resection line – 11.3+2.1%) than in samples colitis ones (42.9±9.9%) p<0.05. It was found that tumour tissue, in contrast to peritumoural tissue, accumulated T-lymphocytes (64.2±3.6% and 51.9±3.6%, correspondingly) due to CD4 cells (35.5±2.3% and 24.3±2.1%, correspondingly, p<0.05). Lower level of B-cells was found in tumour (18.0±2.8% and 30.1±3.7%, correspondingly, p<0.05). Conclusions: abnormalities of local cellular immunity at diseases of large bowel are probably related not only to imbalance of lymphocyte subpopulations, but also to change of local correlation of levels of αβ-T-lymphocytes capable of recirculation, and tissue γδ-T-lymphocytes. This may cause inadequacy of immune protection at cancer of large bowel.
Blood and tumor inflammation markers in non-small cell lung cancer (NSCLC): Blood leukocytosis as an independent risk factor in early stage.
Authors: Carus Andreas , Ladekarl Morten , Hager Henrik , Pilegaard Hans , Nielsen Patricia Switten , Donskov Frede 
Published: March 2020

e21110 Background: Cancer inflammation is associated with impaired survival in a range of cancers. We reviewed blood and intratumoral inflammatory markers in NSCLC. Methods: At the Departmentof Thoracic Surgery, Skejby Hospital, Aarhus, Denmark, consecutive patients with resected NSCLC from 2000 to 2008 were reviewed, and 906 patients with complete clinical data were identified. A subset of 341 consecutive patients, resected between 2003 and 2006, also had intratumoral CD66b+ neutrophils and CD163+ macrophages measured by immunohistochemistry and evaluated by stereological assessment. Results: A total of 526, 197, and 183 patients had stage I, II, and III, respectively. Multivariate analysis stratified for tumor stage revealed elevated blood leukocytes above upper limit of normal as a significant prognostic factor for recurrence-free survival (RFS)(hazard ratio [HR] 1.9; 95% CI 1.4-2.6; p<0.0001), cancer specific survival (CSS)(HR 1.9; 95% CI 1.4-2.7; p<0.0001), and overall survival (OS)(HR 1.5; 95% CI 1.1-1.9; p<0.006) in stage I NSCLC, but not in stage II and III. No prognostic impact of intratumoral neutrophils or macrophages was seen on CSS, RFS, or OS, neither in the entire cohort, nor limited to stage I patients with elevated blood leukocytes or with normal counts. Controlling intratumoral neutrophils and macrophages for localization restricted to tumor tissue, stromal tissue, or blood vessels, respectively, were also with no statistically significant difference. Conclusions: Blood leukocytosis is an independent prognostic factor for short recurrence free survival, cancer specific survival, and overall survival in stage I NSCLC, but not in stage II and III. However, intratumoral neutrophils or macrophages did not impact prognosis. Further studies are needed to elucidate the role of cancer inflammation in NSCLC.
Routine detection of EGFR gene mutations in lung carcinomas: A 2-year single-center experience.
Authors: Vallee Audrey , Sagan Christine , Le Loupp Anne-Gaelle , Theoleyre Sandrine , Dejoie Thomas , Hiret Sandrine , Denis Marc G. 
Published: March 2020

e21117 Background: Activating mutations in the tyrosine kinase domain of the EGFR gene in lung carcinoma has been associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice to predict patient response. We have analyzed the results of the tests we performed during years 2010 and 2011. Methods: DNA was extracted from formalin-fixed paraffin-embedded tissues, following macrodisection, using an iPrep robot (Invitrogen). The p.L858R and p.L861Q substitutions (exon 21) were assessed by allele-specific PCR and exon 19 deletions by PCR amplification followed by DNA fragment analysis (polyacrylamide gel electrophoresis). These techniques allowed us to detect these mutations when present in at least 2% of the cells. Results: During these 2 years, we analyzed samples from 1,041 patients (including 907 adenocarcinomas, 71 large cell carcinomas and 28 squamous cell carcinomas). The EGFR mutational status could not be determined in 51 cases : DNA could not be amplified in 23 cases (2.2%), and 28 samples (2.7%) contained a limited percentage (<10%) of cancer cells. The EGFR status could thus be successfully determined in 990 (95.1%) samples. EGFR mutations were detected in 142 (14.3%) patients : 74 exon 19 deletions, and 68 p.L858R mutation. The mutation rate was, as expected, higher in women (24.0%) than in men (7.2%), and mutated patients were significantly older than non mutated patients (median age : 71 y vs 63 y). Furthermore, the mutation rate was much higher in tumors expressing the TTF-1 antigen (117/638; 18.3%) than in TTF-1 negative tumors (5/228; 2.2%). Similar mutation rates were obtained with primary tumors (89/661; 13.5%) and metastases (40/274; 14.6%), and with surgical specimen (43/325; 13.2%), fiberoptic bronchial biopsies (36/250; 14.4%), CT-guided needle biopsies (25/181; 13.8%) and transbronchial needle aspirates (5/38; 13.2%). Conclusions: The results obtained through routine analysis of more than 1000 samples indicated that our procedure is very efficient. All types of samples can be analyzed without any significant bias. TTF-1 immunostaining might be used to predict for negative EGFR mutation status.
Efficacy of treatment of vulva cancer patients and analysis of their hormonal status.
Authors: Nerodo Galina A. , Nerodo Ekaterina 
Published: March 2020

e21127 Background: hormonodependency of vulva is wellknown. This broughtusto study hormonal status of vulva cancer patients depending on treatment efficacy Methods: we present comparative analysis of hormonal status of vulva cancer patients in two groups: group 1 (50 patients) without relapse of the disease in 5-year period, and group 2 (35 patients) with relapse developed within the first year. Blood concentrations of testosterone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone were determined in all patients under study by means of radiometric methods. Estrone, estradiol, estriol with subsequent calculation of their sum were determined in daily urine by Brown method. Results: In the presence of effect (group 1) initial total amount of estrogens was twice as large than in its absence. In group 1 estradiol concentration exceeded the corresponding parameter of group 2 by three times(7.6±0.6 & 1,4±0.3,p<0.001). The amount of secreting estriol at positive result was almost twice higher than in cases of absence of the effect(10.02±1.7 & 4.6±0.49, p<0.001). The groups differed by secretion levels of follicle-stimulating and luteinizing hormones. Blood concentration of these hormones was lower in negative results that in positive. Distinct differences were also observed in progesterone and prolactin levels. In the group with positive result of treatment progesterone concentration was much higher than in the group without treatment effect. On the contrary, prolactin concentration in group 1 was significantly less than in group 2. The highest degree of reliability of quantitative indices related to treatment efficacy was observed for progesterone. Positive result of corresponding treatment may be predicted at normal initial progesterone level, and negative result at its low level (3-4 times lower than the norm). Another parameter - blood concentration of prolactin - can be used almost with the same degree of reliability. Conclusions: results of the study allow to suggest an existence of interrelation between treatment efficacy of vulva cancer patients and functional activity of hypophysis-gonadal system. Some of its parameters may be used to predict results of complex treatment of vulva cancer patients.
Is serum tryptase level a novel biomarker in colorectal cancer patients?
Authors: Brandi Mario , Gadaleta-Caldarola Gennaro , Ruggieri Eustachio , Ammendola Michele , Patruno Rosa , Goffredo Veronica , Misino Andrea , Montemurro Severino , Gadaleta Cosmo Damiano , Ranieri Girolamo 
Published: March 2020

e21134 Background: Tryptase is a serin protease stored in mast cell granules that plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor activation. On the other hand colo-rectal cancer (CRC) is a well-established angiogenesis dependent tumour and anti-angiogenic based therapy is a standard treatment in metastatic CRC. This preliminary study aims to assess tryptase serum levels in 51 CRC patients before and after radical surgery. Methods: In this study patients with stage B and C CRC (according to Astler e Coller staging system) were selected. Samples of blood were taken from CRC patients between 7 and 9 a.m.1 day before and 1 day after curative surgery. Venous blood was dispensed into a tube for serum (Becton Dickinson Hemogard Vacutainer Systems, Plymouth, UK). Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia,Uppsala, Sweden). Primary tumour tissue were also evaluated in terms of MCs positive to tryptase by immunohistochemistry utilizing an anti-tryptase primary antibody (clone AA1; Dako, Glostrup, Denmark). Results: Mean ± s.d. tryptase level pre-tumour surgical resection was 6.37 ± 4.57 μg/L, and mean ± s.d. tryptase level post tumour surgical resection was 5.15 ± 3.82 μg/L. A statistically significant difference between pre-tumour surgical resection and post-tumour surgical resection tryptase level concentrations was found: p=0.000 by t-test. A statistically significant correlation between MCs positive to trypase and serum tryptase levels pre-surgical resection was also found (r=086; p=0.000) by Pearson’s analysis. Conclusions: This pilot report analyzes the possible significance of serum tryptase levels changes in CRC patients who underwent curative surgery. Our results demonstrated higher serum tryptase levels CRC patients suggesting the release of tryptase from MCs of primary CRC tissue. As expected, after radical surgical resection, serum tryptase levels had decreased. We suggest that tryptase may play a role as a new predictive biomarker in CRC patients. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated as adjuvant treatment in clinical trials.
The level of FSHR expression in the primary kidney tumors to predict the response to subsequent antiangiogenic therapy with sunitinib.
Authors: Siraj Muhammad Ahsan , Pichon Christophe , Radu Aurelian , Ghinea Nicolae 
Published: March 2020

e21138 Background: Sunitinib is an antiangiogenic receptor tyrosine kinase inhibitor used to treat advanced metastatic renal cell carcinoma and other types of cancer. Sunitinib is effective in only approx. 70% of clear cell renal cell carcinoma (CCRCC) patients, has significant adverse side effects, and no method is available to predict which patients will not respond. Our purpose was to explore the possibility of introducing an effective prediction method based on a marker of the tumor vasculature, the Follicle Stimulating Hormone Receptor (FSHR). Methods: Using immunohistochemistry on paraffin sections with anti-FSHR monoclonal antibodies we studied by photonic and fluorescence microscopy the expression of FSHR in 50 patients diagnosed with advanced metastatic CCRCC. All patients were subjected to surgery for removal of the primary tumor and were subsequently treated with sunitinib orally for ≥ 3 months with a dose of 50 mg/day for 4 weeks followed by 2 weeks off. After therapy the patients were categorized as “responsive”, “stable”, or “non-responsive” based on the RECIST guidelines. The blood vessel density and the percentage of FSHR-positive vessels were determined by immunofluorescence on sections from the primary tumors removed by surgery, prior to the sunitinib treatment. Von Willebrand factor (vWF) was used as specific endothelial marker. Results: There were no significant differences in the total density of vessels (detected with anti-vWF antibody) among the responsive, stable and non-responsive patients. The percentage of FSHR-stained vessels was on average five fold higher for the patients that responded to the treatment in comparison with the stable group and almost eight fold higher than in the non-responsive group. The percentage allowed the detection of responders with 87-100% sensitivity and specificity. Conclusions: The data suggest that FSHR expression levels in the blood vessels of CCRCC primary tumors can be used to predict, with high sensitivity and specificity, the patients that will respond to sunitinib therapy.
Thromboembolic complications in cancer patients.
Authors: Yenidunya Gulsah , Turna Hande , Ozturk Mehmet Akif , Tural Deniz , Selcukbiricik Fatih , Yildiz Ozcan , Ozguroglu Mustafa , Demirelli Fuat , Buyukunal Evin , Serdengecti Suheyla 
Published: March 2020

e21143 Background: Thromboembolic events are frequent and important complications causing mortality and morbidity in cancer patients.To determine the charecteristics of these events can help us to determine the patients who have higher risks for thromboembolism. Methods: Characteristics of clinically or radiologically determined thromboembolic events were retrospectively analayzed from files of cancer patients followed up in the outpatient oncology clinic of Cerrahpasa Medical Faculty of Istanbul University. Results: A total of 267 thromboembolic events were analyzed.Events were encountered mostly in the venous system, only 3% were in the form of arterial embolism.Venous events were in the form of deep vein thrombosis (67%), pulmonary embolism (16.5%), vena cava superior thrombosis (2.6%), superficial migratory thrombophlebitis (0.4%) or two different forms occuring concomitantly(10.5%). Thromboembolism was determined most frequently in patients with gastrointestinal tumors (41.9%), lung cancer (22.1%) and gynecological tumors (12.1%). The most frequent histopathology was adenocarcinoma (72.4%).Thromboembolic complications were mostly in the form of lower extremity deep venous thrombosis in patients with gastointestinal, gynecological and urogenital tumors where as in the form of pulmonary embolism and vena cava superior thrombosis in patients with lung cancer. Nearly half of the patients with pulmonary embolism (%48.%) were asymptomatic and were diagnosed incidentally with radiological imaging. Upper extremity thrombosis were frequently encountered in patients with venous port a-cath system Most of the patients (87.7%) had metastatic cancer and were receiving chemotherapy (65.5% ) when the event occured. Cisplatin, 5–FU and gemcitabine were the most frequently used chemotherapy agents.Thromboembolic events related to cancer surgery occured usually (59%) in the first month after surgery.Recurrent thromboembolic events were determined in 8.9% of patients mostly whom had gastrointestnal primary tumors (54%). Conclusions: Characteristics of thromboembolic events can help to determine the patients who have higher risk for thromboembolism and predict types and time of the event and provide anticoagulation without delay.
Effect of obinutuzumab (GA101), a type II glycoengineered monoclonal antibody targeting CD20, against rituximab resistant and sensitive cell lines in B-cell non-Hodgkin lymphoma.
Authors: Tiwari Aradhana , Ayello Janet , Van de ven Carmella , Cairo Mitchell S. 
Published: March 2020

e21150 Background: : Relapse or insufficient response or resistance to Rituximab (RTX) has evolved as a challenge in therapy of B-cell NHL. RTX in combination with FAB chemotherapy is a safe, well tolerated and associated with > 90% EFS in children with advanced mature B-Cell NHL (Cairo M.S. et al, ASCO 2010). Obinutuzumab (GA101), a novel type II glyco-engineered CD20 antibody of the IgG1 isotype, demonstrates superior cell death induction and its glycoengineered Fc region has shown to cause significantly enhanced ADCC (Mössner et al, Bld 2010; Niederfellner G. et al, Bld 2011). We evaluated the efficacy of GA101 against Raji (Burkitt Lymphoma), a RTX sensitive cell line (RSCL) and RTX resistant cell lines(RRCL), Raji-2R and Raji-4RH, respectively (generously supplied by M. Barth, MD, Roswell Park Cancer Center, Buffalo, NY. Barth M. et al, ASH 2010). Methods: All cell lines were cultured in RPMI with 10% FBS and incubated with escalating doses of GA101 (1-1000 µg/ml) for 24 hrs (n=10), 48 and 72 hrs (n=6). Cell death was evaluated by staining with AnnexinV/7AAD and flow-cytometry. B-Cell Lymphoblastic Lymphoma (BLL) U-698-M cells (CD20+) were used as the positive and Loucy cells (CD20-) (T-ALL) were used as the negative controls. Results: At 48 hrs 100 µg/ml of GA101, Raji and U-698-M demonstrated highest cell death of 33.62±5.7% and 37.8± 3.9%, respectively; while Raji-2R and Raji-4RH cell death was 22.8±1.8% and 10.31±0.81% (p<0.02) and (p<0.001) respectively. At 1000 µg/ml of GA101 at 24 hrs, Raji demonstrated increased cell death 40.27±9.1% compared with Raji2R 14.1±0.07 and Raji4RH 20.3± 3.2 (p<0.001) and (p<0.001) respectively. Conclusions: GA101 represents a promising candidate for treating RTX resistant B-Cell Lymphomas and related CD20+B-Cell malignancies. Further studies should aim to identify novel approaches such as combination with activated NK Cells or chemotherapeutic agents that may enhance or synergize with the efficacy of GA101. Further investigations aim to elucidate the mechanisms responsible for minimal cell death induction on the U698M and Raji cell lines.