bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of p53 gene transfection on proliferation, apoptosis, and radiosensitivity of cervical cancer cells.
Authors: Li Xiaofan , Wen Shao , Zhang Shanwen 
Published: March 2020

e22024 Background: To investigate the effects of p53 gene transfection on proliferation, apoptosis and radio-sensitivity of cervical cancer cells. Methods: Two cervical cell lines: Siha with wild-type p53 gene and C33a with mutant p53 gene, were transfected with human wild-type p53 gene. Un-transfected cells and transfected cells were exposed to 6 Gy of radiation. Cell proliferation, apoptosis, and protein expressions of p53, MDM2, p21, and bax in the un-treated, p53- transfected, and irradiated cells were analyzed. Results: The protein expression of p53, MDM2, p21, and bax in the untreated Siha cells is very low; High level p53 and MDM2 proteins and low level of p21 and bax proteins were found in the untreated C33a cells. When transfected with recombinant adenoviral human wild-type p53 gene (rAd-p53) the protein levels of p53, MDM2, p21, and bax in both Siha and C33a increased. Highest levels of these proteins were detected at 48 hours after transfection. The increased protein expressions were accompanied with inhibition of cell proliferation. At 72 hours after transfection, 12.3% and 5.5% of Siha and C33a cells became apoptotic, respectively. When exposed to 6 Gy of radiation after 48 hours of the transfection, 46.2% and 38.3% apoptotic Siha and C33a cells were detected, respectively; but only 5.6% and 6.3% of apoptotic cells of their un-transfected counterparts detected at 24 hours after the radiation treatment. Conclusions: Wild-type p53 gene transfection can inhibit cell proliferation, promote apoptosis, and sensitize to radiation of both Siha and C33a cells. The effects on Siha cells are stronger.
A phase II clinical trial of neoadjuvant therapy with zoledronic acid for operable breast cancer.
Authors: Nakayama Yoshie , Takahashi Shunji , Ito Yoshinori 
Published: March 2020

e22027 Background: The neoadjuvant use of bisphosphonates has been reported to increase rates of pathological response in patients with operable breast cancer. We conducted a study to determine whether treatment with zoledronic acid (ZOL) would improve outcomes in such patients when it was added to standard neoadjuvant chemotherapy (NAC). Methods: From April 2010 to June 2012, 30 patients with HER2-negative operable breast cancer were eligible for the study. The patients received NAC (4 cycles of CEF: intravenous epirubicin 100mg/m2, cyclophosphamide 500mg/m2, and fluorouracil 500mg/m2 on day 1, then 12 cycles of weekly paclitaxel 80mg/m2) with ZOL. The ZOL was administered after each cycle of NAC in a 4-mg dose by intravenous infusion every 3 to 4 weeks. The primary end point of the study was pathological response (pPR) rate. The secondary end points were pathological complete response (pCR) rate, adverse effects (AEs) and the changes in the numbers of disseminated tumor cells (DTC), circulating tumor cells (CTC), and circulating endothelial cells (CEC). We evaluated the efficacy and safety of ZOL in the NAC in patients by use of Fisher’s exact test. Results: 29 patients completed surgery after NAC, and pathological analyses and the numbers of CTC and CEC were assessed. Two patients had progressive disease during NAC, with brain metastasis and bone metastasis, respectively. The pPR rate, pCR rate, was 31.0%, 10.4%, respectively. CTC were detected in 3 patients at baseline, and CTC had changed to positive in one patient in D15 of the first cycle, then after NAC, all four patients changed to negative. CTC were negative in two patients at baseline, but after NAC, changed to positive. There were no factors associated with the change rates of CTC. CEC after NAC increased from baseline significantly (p<0.001). The increase rates of CEC were not significantly different among premenopausal and postmenopausal, PR and non-PR, and luminal and triple negative patients. There were no severe AEs associated with ZOL to discontinue treatment. Conclusions: These data suggested ZOL in combination with NAC might not have a significant direct anti-tumor effect. Change of CEC would be a biomarker for NAC, but further analyses would be necessary. Clinical trial information: 000003498.
3D morphometric analysis to yield high sensitivity and specificity enumeration of circulating tumor cells.
Authors: Meyer Michael , Neumann Thomas , Katdare Rahul , Presley Chris , Hayenga Jon , Hawthorne Ben , Nelson Alan 
Published: March 2020

e22031 Background: The enumeration of circulating tumor cells (CTCs) has become a common method to assess cancer treatment efficacy. In this study, we propose to test our ability to detect and enumerate CTCs using a morphometric classifier based on 3D cell features to distinguish normal cells from lysed blood and breast cancer cells. Methods: Commercially available normal whole blood was lysed to destroy red blood cells, leaving white blood cells and some cell debris. These cells and breast cancer cells from the SK-BR-3 cell line were studied. The cells were stained with hematoxylin, then were automatically imaged using VisionGate’s 3D cell imaging system (Cell-CT) that unambiguously renders individual cells with isometric, sub-micron resolution. Image libraries of cells were created. For each cell, 683 morphology features were computed. Features characterize various aspects of the cell such as chromatin distribution in the nucleus, nuclear volume and shape and nuclear to cell volume ratios. The true cell diagnosis for each cell was determined by a cytotechnologist and added to the feature set. Cross-validated classifiers were created using the technique of adaptive boosting that combines a sub-set of the features into a single score that best correlated with the binary cell diagnoses. Results: 3,256 normal cells or other normal objects and 1,843 breast cancer cells were studied. A classifier that distinguished normal cells from cancer cells was created that used the strongest 25 3D morphology features. The morphometric classifier had an area under the ROC curve that measured 0.9998. This classifier could be operated with near perfect specificity and a cancer cell sensitivity of 95%. Conclusions: Performance of automated, 3D morphometric classifiers for cancer cell detection suggests highly accurate CTC enumeration with implications for patient management and prediction of cancer progression.
The impact of sex on ropporin expression in multiple myeloma patients.
Authors: Wade Raymond , Radhi Saba , Chiriva-Internati Maurizio , Hardwick Fred , Mer Jesse , Aulakh Amardeep , Saadeh Charles , Yu Yuefei , Mirandola Leonardo , Zepeda Kristopher , Chiaramonte Raffaella , Colombo Michela , Platonova Natalia , Nguyen Diane Duyen Thuy , D'Chuna Nicholas , Konala Venu , Jenkins Marjorie , Figueroa Jose A. , Cobos Everardo 
Published: March 2020

e22052 Background: Multiple myeloma (MM) is a cancer of plasma cells wherein aberrant cells accumulate in the bone marrow leading to bone damage and interference with normal blood cell production. Although MM remains incurable, it is treatable. As with most forms of cancer, early detection is the key to improving prognosis and avoiding permanent damage. Cancer Testis Antigens (CTAs) are a class of proteins that are expressed in male gametogenic tissue but generally not in the somatic tissue of healthy adults. However, a number of cancer types have been shown to produce these proteins, and their expression has been correlated with malignancy. Ropporin is a specific CTA shown to be associated with MM, and this protein represents a potential target for MM diagnosis as well as immunotherapy. In this study, we examine the impact of sex on the expression of Ropporin, in MM patients. Methods: The expression of this particular CTA in MM patients was analyzed using PCR, ELISA, and immunohistochemistry in a cohort of 59 MM patients (37 male and 22 female). Results: 61% of MM patients were positive for Ropporin expression. When the data were broken down by sex, it was revealed that Roporrin expression was 81.8% in females and 48.6% in males. Interestingly, 50% of female patients as well as 78% of males expressing Ropporin were deceased. In addition, 100% of the deceased subjects in the cohort were Ropporin positive. Conclusions: Our results provide indications that sex can shift the expression of CTA in multiple myeloma. Furthermore, the data indicate CTA expression may affect the prognosis in MM patients. Further studies in a large cohort of patients are warranted to validate the correlation of CTA/ropporin in MM patients and sex.
Can serum thioredoxin levels predict sensitivity to platinum in lung cancer?
Authors: Dinh Vy Thuy , Wangpaichitr Medhi , Nguyen Dao M. , Matsangou Maria , Wu Chunjing , Ahn Eugene , Savaraj Niramol 
Published: March 2020

e22062 Background: Our laboratory has found that cisplatin resistant lung cancer cells possess high levels of ROS (reactive oxygen species). Low intracellular TRX1 (thioredoxin) levels due to increased secretion of the thioredoxin-1 (TRX1) is the primary reason for high intracellular ROS levels. We have further shown that reconstituting TRX1 protein in cisplatin-resistant cells can restore sensitivity to cisplatin. Conversely, silencing TRX1 in parental cells reduced the sensitivity to cisplatin (MCT11:604, 2012). Thus, it is possible that serum TRX1 levels may be a useful marker to predict sensitivity to platinum containing regimens. Methods: Serum samples were obtained before, during, and after platinum chemotherapy. TRX1 was determined by sandwich ELISA with two TRX1 antibodies. Samples, standards, and reagent blank were incubated with precoated plate (IBL). Labeled antibody solution was added followed by Chromagen substrate and subjected to plate reader. The value on normal healthy individual is less than 5 ng/ml. The lowest limit of detection is 1 ng/ml. Results: 11 patients (pts) were entered into the study. 6 pts had small cell lung cancer (SCLC) and 5 had non small cell lung cancer (NSCLC). 2 SCLC pts died before treatment and couldn’t be assessed and 2 pts are too early to assess response. In these lung cancer pts, the baseline levels ranged from 0 to 96.5 ng/ml. Thus far, 4 pts (1 SCLC and 3 NSCLC) who had baseline TRX1 levels of 0, 0, 0 and 3 responded to chemotherapy. An additional SCLC pt with very high levels of TRX1 (96) also responded to chemotherapy. However, this pt also had a recent operation for NSCLC and the baseline blood sample was obtained after the operation, which may not be the appropriate baseline. 2 pts with baseline TRX1 levels of 31.1 and 6.5 did not respond to treatment. TRX1 levels increased during chemotherapy, especially when given concurrently with radiation. However, in pts who responded, TRX1 levels decreased at the end of treatment. Conclusions: The study is currently ongoing. Our initial results suggest that low TRX1 levels may indicate possible future response to platinum containing regimens. While TRX1 levels may increase during treatment, in pts who respond to treatment, TRX1 levels often decrease back to baseline.
Prevalence and quantity of circulating tumor cells (CTCs) after adjuvant chemotherapy in patients with HER2-negative early breast cancer (EBC).
Authors: Schochter Fabienne , Andergassen Ulrich , Neugebauer Julia Katharina , Friedl Thomas W. P. , Pestka Aurelia , Jueckstock Julia Kathrin , Jaeger Bernadette , Salmen Jessica Christine , Hepp Philip Gm , Heinrich Georg , Camara Oumar , Decker Thomas , Ober Angelika , Fehm Tanja N. , Pantel Klaus , Fasching Peter A. , Schneeweiss Andreas , Beckmann Matthias W. , Janni Wolfgang , Rack Brigitte Kathrin 
Published: March 2020

e22075 Background: Prevalence of CTCs after adjuvant chemotherapy in patients with EBC might indicate both treatment response and prognosis. Here we present data on CTC prevalence and quantity assessed after chemotherapy in correlation with tumor characteristics and chemotherapeutic treatment in patients with Her2-negative EBC from the German SUCCESS C study. Methods: The SUCCESS C trial is a randomized, open-label, Phase III study comparing disease free survival (DFS) in patients with HER2-negative EBC treated with either 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC) followed by 3 cycles of Docetaxel(DOC), or 6 cycles of a anthracycline-free regimen with Docetaxel-Cyclophosphamide(DOC-C). The CTC status at chemotherapy cycle 6 was prospectively evaluated using the FDA-approved CellSearch System (Veridex, USA). Results: Valid data on CTC status after chemotherapy were available for 2,336 patients (78% estrogen receptor positive, 6% pT3 or pT4, 12% pN2 or pN3). CTCs were found in 278 (11.9%) patients (median 1, range 1 – 69 CTCs). One CTC was detected in 164 (59%), two CTCs in 57 (21%), three to five CTCs in 45 (16%), and more than five CTCs in 12 (4%) of these patients. CTC prevalence was not significantly associated with tumor size (pT1, pT2, pT3, pT4), nodal stage (pN0, pN+), grading (G1, G2, G3), histological type (invasive ductal, invasive lobular, other), estrogen receptor status, progesterone receptor status, or treatment arm (FEC-DOC, DOC-C), as revealed by both univariate analyses (Chi-square tests, all p > 0.1) and a logistic regression with CTC prevalence as dependent variable. Conclusions: In about 12% of patients with Her2-negative EBC, CTCs in the peripheral blood were detected at the end of adjuvant chemotherapy treatment. However, neither CTC prevalence nor quantity of CTCs were related to tumor characteristics or type of chemotherapeutic regimen. The low rate of CTC-positive patients might be attributed to the negative HER2 status and reflects therefore the relatively low risk of these patients to develop metastatic relaps. Clinical trial information: NCT00847444.
Relationship between EGFR Intron-1 CA SSR 1 polymorphism and skin rash in patients treated with cetuximab.
Authors: Nawrocki Sergiusz , Rucinska Monika 
Published: March 2020

e22087 Background: EGFR inhibiting drugs do not work equally effectively in cancer patients. We were looking for potential genetic factors which could help to select patients who benefit from treatment with cetuximab. One of established clinical factors is skin rash, which correlate with clinical response to EGFR inhibitors. Our hypothesis was that rash intensity depends on genetic polymorphisms of gene encoding EGFR, especially on Intron-1 CA SSR 1 polymorphism. The number of CA repeats in Intron-1 may affect the level of preRNA synthesis. Methods: The prospective study included 62 patients (colon cancer, head and neck, non-small cell lung cancer and gastric cancer) who were treated with cetuximab together with chemotherapy. 4 weeks after the start of treatment with cetuximab, rash intensity was assessed according to NCI CTAEv.3.0. criteria. DNA for analysis was isolated from 5 ml of peripheral blood. Using the PCR reaction with specific primers (polymorphic DNA segment was amplified. The obtained DNA fragments were analysed by GenScan to determine their lengths. Results: Patients with 15-18 “CA” repetitions were classified as having a short allele “S”, while patients with 19-22 “CA” repetitions have been marked as having a long allele “L”. The relationship between the rash intensity and the CA-polymorphism was assessed (Table). The analysis showed that there is tendency to more intensive rash in patients with pair of “short” alleles (SS), than in patients with “short-long” (SL) and “long” (LL) allelles (p<0,1 chi-square test). Conclusions: There is a relationship between the EGFR Intron-1 CA-polymorphism and the rash intensity in patients treated with cetuximab which warrants further prospective clinical investigation. [Table: see text]
Molecular subtyping of breast cancer using dedicated breast PET-CT.
Authors: Pinker-Domenig Katja , Magometschnigg Heinrich , Mayerhoefer Marius , Dubsky Peter Christian , Bartsch Rupert , Bago-Horvath Zsuzsanna , Karanikas Georgios , Weber Michael , Helbich Thomas 
Published: March 2020

e22090 Background: Recently dedicated breast 18FDG breast PET-CT has emerged as an additional imaging tool for assessment and staging of primary breast cancer. Expression of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status, has direct prognostic and therapeutic implications in patient management. This study aimed to determine whether correlations exist between 18FDG up-take of the primary breast cancer lesions and these predictive and prognostic factors. Methods: Before undergoing surgery 114 patients with primary breast cancer underwent 18FDG breast PET-CT. The maximum standardized uptake value (SUVmax) of the primary breast cancer was measured in each patient and standard immunohistochemistry was performed on a surgical specimen to characterize the receptor state of tumor cells. Appropriate statistical tests were used to test for any association that may exist among ER, PR, and HER2. Results: A significant association was found between a triple negative status and the SUVmax (p < 0.001) of breast tumors. ER-negative tumors (mean SUVmax, 10.4) demonstrated a significantly higher SUVmax than did ER-positive tumors (median SUV, 5.1) (p= 0.045). No statistical significant difference was found for SUVmax of PR-negative vs. PR-positive lesions with a mean SUVmax of 8.6 and 4.9 (p=0.15) respectively. No statistical significant difference was found for SUVmax of HER2-negative vs. HER2-positive lesions with mean SUVmax of 6.4 and 5.3 respectively (p=0.55). If either ER or PR was positive, then the other tended to be positive as well (chi2 = 84%, P < 0.01). No such significant relationship was detected between PR or ER and HER2 (P > 0.05). Conclusions: ER-negative breast cancer tumors display higher 18FDG uptake than ER-positive tumors. Triple-negative breast tumors are associated with increased 18FDG uptake commensurate with their aggressive biology. The data suggest that SUVmax measurements of 18FDG breast PET-CT can provide valuable information about the state of ER, PR, and HER2 and the associated glucose metabolism of the primary breast cancer lesions. Such an association may be of importance to treatment planning and outcome in these patients.
Targeting angiogenesis driven by fibroblast growth factor using RPT835, an FGFR2 inhibitor.
Authors: Stepanova Evgenia , Solomko Eliso , Ryabaya Oxana , Peretolchina Nina , Tsimafeyeu Ilya , Tjulandin Sergei 
Published: March 2020

e22097 Background: The fibroblast growth factor (FGF)/FGF receptors (FGFR) signaling axis plays a key role in driving tumor angiogenesis. There is little data on the targeting of FGF-induced angiogenesis. We describe here the targeting angiogenesis driven by FGF using RPT835, novel inhibitor of the FGFR2 extracellular domain (received from RusPharmTech, LLC). Methods: To assess the efficacy of RPT835 on FGF-mediated endothelial cells proliferation, the human umbilical vein endothelial FGFR-expressing cells (HUVEC) were incubated in a 96-well microculture plate and were treated with serially diluted RPT835 or Brivanib as a control. Basic FGF was added at a concentration of 25 ng/ml. Control wells were left untreated. Cell growth inhibition was determined using Promega’s Cell Titer-Glo assay. In vivo angiogenesis was measured with subcutaneously implanted Matrigel plugs containing bFGF (100 ng/ml) or bFGF (100 ng/ml) + bevacizumab (10 mg/kg) or bFGF (100 ng/ml) + RPT835 (15 mg/kg). Control group was without stimulation and treatment. Each group included 3 mice. Number of endothelial cells/vessels was calculated. Results: Basic FGF significantly increased proliferation of the HUVEC cells (P=0.001) in untreated control group. RPT835 significantly inhibited FGF-triggered endothelial cell proliferation when compared with control (P<0.001) or brivanib (P<0.001, IC50=289 nmol/L) with IC50 of 11 nmol/L. In vivo, bFGF induced proliferation of endotheliocytes and mature vessels formation (P<0.001). There were no vessels in FGFR2 inhibitor group. Bevacizumab did not decrease number of vessels in comparison with FGF-stimulated angiogenesis (P=0.9). Conclusions: Inhibition of bFGF/FGFR2 pathway resulted in effects on endothelial cells proliferation andmature vessels formation. Bevacizumab had no activity in FGF-induced angiogenesis.
Association of tumor-specific GPR87 overexpression with poor prognosis in non-small cell lung cancer.
Authors: Nii Kazuhito , Liu Dage , Tokunaga Yoshimasa , Zhang Xia , Ishikawa Shinya , Haba Reiji , Kakehi Yoshiyuki , Yokomise Hiroyasu 
Published: March 2020

e22108 Background: GPR87 is a member of G-protein-coupled receptors (GPCRs). Recently, GPR87 was suggested to contribute to the viability of human tumor cells, and the overexpression of GPR87 mRNA was found in many malignant tumors including lung cancer. However, the clinical significance of GPR87 expression in non-small cell lung cancer (NSCLC) has not been well studied. Methods: 127 NSCLC patients who underwent surgery from 1999 to 2004 were investigated. There were 59 adenocarcinomas, 55 squamous cell carcinomas and 13 others. The intratumoral expression of GPR87 was evaluated by immunohistochemistry. The Ki-67 proliferation index was also evaluated. Results: A tumor-specific expression of GPR87 was found in NSCLC in comparison with the surrounding normal tissue. Fifty-nine tumors (46.5%) were found to be high-GPR87 tumors. The high-GPR87 tumors were more frequently found in squamous cell carcinoma than in adenocarcinoma (60.0% versus 37.3%, p=0.02). Regarding the tumor proliferation, the Ki-67 index was significantly higher in high-GPR87 tumors than in low-GPR87 tumors (p=0.04). There was a tendency that the overall survival was worse in patients with high-GPR87 tumors than in low-GPR87 tumors (p=0.22). For the patients with adenocarcinoma, the overall survival was significantly worse in patients with high-GPR87 tumors than in low-GPR87 tumors (p=0.04). Conclusions: GPR87 expression may become a poor prognostic predictor for patient with NSCLC, especially for those with adenocarcinoma. GPR87 may contribute to the cell viability by promoting cell proliferation, has a potential to become a novel therapeutic target for cancer treatment.