bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance of histology type between synchronous and metachronous contralateral breast carcinoma: Is there susceptibility for breast cancer of particular histology?
Authors: Tomasevic Zorica , Gavrilovic Dusica , Tomasevic Zoran , Kolarevic Daniela 
Published: March 2020

e21030 Background: Contra-lateral breast cancer (CBC) is considered to be the most frequent new malignancy after primary breast cancer (PBC) However, there are few reports whether the histology and other major molecular characteristics differs between PBC and CBC. The aim of this paper is toevaluate and compare PBC/CBC histology according to the time to CBC development. Also, age at CBC and major molecular characteristics (tumor grade, estrogen/progesterone receptors, HER2) have been analyzed. Methods: A cohort of 113 patients with CBC, without distant metastases, has been prospectively registered during 28 months. Patients are divided in 2 groups according to the time of CBC diagnose: 1. Synchronous, if the CBC (S-CBC) was diagnosed either simultaneously or within 6 months after PBC; 2. Metachronous (M-CBC) if CBC was diagnosed > 6 months after PBC. Results: Results are presented in Table 1. Median age was calculated at the time of CBC diagnose. Patient with S-CBC are median 7 years older than patients with M- CBC that is statistically significant difference (p-0.007) S-CBC is more likely to be of the same histological type (76%) than M-CBC (56%) (p 0.006) In the whole analyzed group, and each subgroup separately, lobular carcinoma is registered in higher percentage (41%) than expected (~20%) For all other analyzed BC characteristics, statistical difference was not confirmed, however ~ 25% of specimens were not available for testing. Conclusions: Although it is still unclear what could be the clinical significance of these findings, genetic susceptibility to particular histology type of BC might be reasonably speculated. [Table: see text]
Plasma TS mRNA expression as a potential predictive biomarker for pemetrexed and raltitrexed in gastric cancer.
Authors: Liu Baorui , Shen Jie , Wang Hao , Wei Jia , Yu Lixia , Xie Li , Qian Xiaoping , Zou Zhengyun , Guan Wen xian 
Published: March 2020

e21034 Background: Plasma mRNA opens up new investigational opportunities and has great potential for use in disease and treatment assessment. Pemetrexed and raltitrexed are novel water-soluble quinazoline folate analogues and act as direct and specific TS inhibitors. Although TS expression levels detected in tumor have shown potential in predicting sensitivity to those two chemotherapeutic agents, current knowledge is limited on the role of plasma TS mRNA as a predictive biomarker. The aim of this study was to investigate the association between plasma TS mRNA expression and in vitro chemosensitivity to pemetrexed and raltitrexed in gastric cancer. Methods: 150 freshly-removed gastric tumor specimens and corresponding blood samples before surgery were collected. Pemetrexed and raltitrexed sensitivity was determined by histoculture drug response assay (HDRA) procedures. Plasma and tumor TS mRNA expression level were determined by quantitative RT-PCR. Results: A significant correlation was observed between plasma and tumor TS mRNA expression levels (rho=0.665, P<0.001). Plasma TS expression level was negatively correlated with in vitro sensitivity to pemetrexed and raltitrexed in gastric cancer (pemetrexed-sensitive sub-group: 0.90, 95% CI: 0.66-1.16; pemetrexed-resistant sub-group: 1.82, 95% CI: 1.38-2.26, P<0.001; raltitrexed-sensitive sub-group: 0.91, 95% CI: 0.64-1.22; raltitrexed-resistant sub-group: 1.62, 95% CI: 1.06-2.17, P=0.013). There was no significant association between clinical characteristics and plasma TS mRNA levels or in vitro chemosensitivity. Conclusions: Our results indicated that plasma TS mRNA expression could be a prominent predictive biomarker for raltitrexed in gastric cancer, enabling the development of ‘‘real-time’’ individualized chemotherapy while tumor progression.
Importance of serum VEGF and basic FGF levels in determining response to treatment and survival in patients with metastatic colorectal cancer.
Authors: Keskin Muge , Ustuner Zeki , Dincer Murat , Etiz Durmus , Celik H.Eray , Gulbas Zafer 
Published: March 2020

e21050 Background: Colorectal cancer has an important place in worldwide death from cancer causes. Angiogenesis, in which angiogenic factors such as VEGF and basic FGF have a key role, is an important factor in patient survival with respect to progression and metastatic spreading in colorectal cancer. In this study, we aimed to determine that whether serum VEGF and bFGF pre- and post-treatment serum levels are decisive in evaluating response to treatment and progression in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI-bevacizumab. Methods: In 33 mCRC patients treated in our department serum VEGF and bFGF levels were monitored in the beginning of treatment and until progression during FOLFIRI-bevacizumab treatment before 4.-, 8.- and 12.-regimens. Serum levels of VEGF and bFGF were assssed using the quantitative sandwich enzyme immunoassay technique. Results: In our study serumVEGF and bFGF levels were significantly higher than the healthy controls (p<0.001). We found that the patients with pre-treatment high serum bFGF levels have significantly short PFS and with pre-treatment high serum LDH levels have significantly short overall survival (OS). In patients with pre-treatment low serum VEGF value (< 147.79 pg/ml) had significantly longer OS (27.93 vs 23.27 mounts, P:0.026) in metastatic rectum cancer. In multivariate analysis were found to be prognostic factors VEGF levels and side of tumor for PFS and VEGF levels and whether to be operated of tumor for OS. Conclusions: Serum VEGF level was detected to be one of the factors that determine PFS and OS in mCRC. Pretreatment serum bFGF levels were determined PFS and monitorization of serum bFGF during treatment was found to be releated to response to treatment. Pretreatment serum LDH level was detected to determine OS in metastatic CRC. Although there was no statistical significance, in mCRC patients, whose pretreatment serum VEGF were high, PSK was longer with bevacizumab treatment. The important of pretreatment high serum VEGF level to select for treatment of bevacizumab will be planed in metastatic CRC requires to be confirmed in comprehensive, prospective studies.
The influence of mammaplasty on axillary lymphatic drainage patterns and sentinel lymph node detection: A 40-patient prospective study including the 20 first patients of the preliminary study.
Authors: Gremillet Eric , Soler Claude , Bouteille Catherine , Steiner Aline , Geissler Benjamin 
Published: March 2020

e21056 Background: In the field of sentinel lymph node (SLN) for patients with previously breast surgery, opinions are not definitive. On the first hand, the ASCO in 2005 recommended that SLN biopsy should not be performed in patients with previous mammaplasty or axillary surgery, but, on the other hand, the same panelists of the ASCO guideline suggested that a preliminary lymphoscintigraphy (LSG) could be done when considering a SLN biopsy in patients with previous mammaplasty, with the objective of verifying the integrity of axillary nodes. We started a prospective study in January 2009, to evaluate the location of sentinel lymph node (SLN) before and after mammaplasty. The preliminary results of the first 20 patients were presented in June 2010 (Chicago, ASCO), however it was to be necessary to have more patients to validate these encouraging results. The results of additional study is presented here. Methods: 40 patients who underwent mammaplasty were evaluated by LSG acquired with a SPECT-CT immediately after intradermal periareolar injections of 99mTc -labelled sulphur colloid at two time points: before mammaplasty (Pre-LSG) and between 40 to 60 days after mammaplasty (Post- LSG). Results: The localisation of hot SN was evaluated as in the first study, using the SPECT-CT images : - antero-posterior distance was estimated in centimeter from SLN region to dorsal vertebrae spine center. - SLN’s coronal position was compared to rib cage. The average value of 40 antero-posterior distance before and after surgery was 14.2 vs 14.4 centimeters, in the preliminary study it was 13.6 vs 13.8 centimeters, the difference keeps the same between 2 studies (2 millimeters). As in the first study, SN was in the same position in relation to grill rib. The binomial test did not show statistical difference in lymphatic drainage patterns between Pre-LSG and Post-LSG. Conclusions: after evaluating the impact of the previous mammaplasty surgery on the SLN position, we observed that surgery did not modify lymphatic mapping and thus that it may be possible to propose SLN biopsy even after mammaplasty. This study confirms the results of our preliminary study.
Differential frequency of breast cancer molecular profiling by socioeconomic status in San Diego, California.
Authors: Vosganian Gregory Sumpao , Rosenberg Joshua Daniel , Verman Radha , Waalen Jill , Mason James R. 
Published: March 2020

e21061 Background: Previous reports demonstrate inferior outcomes for cancer patients of low socioeconomic status (SES). The development of breast tumor molecular profiling has optimized anticancer therapy but its effect on outcome for those with barriers to care is unknown. Methods: Breast cancer patients appropriate for OncotypeDX testing (Genomic Health, Inc) were identified from The Scripps Health Tumor Registry. High SES was defined as patients residing in zip codes with a median household income in the top quartile for the county according to the San Diego Association of Governments. Low SES was defined as patients residing in zip codes with median income in the bottom quartile or with Medical as primary insurance. The frequency of OncotypeDX testing, result, therapy prescribed, relapse and cancer specific death rates are reported. Statistical analysis was performed by unpaired t-test; p values≤0.05 were considered significant. Results: 2,192 early-stage breast cancer patients were identified; 167 met criteria. Patients were younger (p<0.0001) and a lower rate of OncotypeDX testing was noted in the low SES group (p=0.028); no difference in stage was observed. All patients were prescribed anti hormone therapy but the low SES group received chemotherapy more frequently (p=0.0075). No difference in relapse rate and no deaths attributable to cancer were noted. Conclusions: We observed a lower rate of OncotypeDX use in the low SES cohort. While the cause is unclear, the higher rate of chemotherapy use in this group may represent overtreatment. Determining a survival impact attributable to this difference requires longer follow-up. Our data demonstrate the need for prospective analysis of tumor profiling use in low SES individuals to ensure early stage breast cancer patients receive optimal therapy. [Table: see text]
Differential gene expression associated with the tropism between hepatic and pulmonary metastases in colorectal cancers.
Authors: Kim Sung-Hyun , Choi So-Jung , Lee Jinseon , Kim Jhingook 
Published: March 2020

e21062 Background: In metastatic colorectal cancers tumor cells were already disseminated, prior to surgical resection of the primary tumors, but micrometastases remain dormant until proper colonization mechanisms are activated. Specific aims of this study are, 1) to examine the colonization pathways and genes newly activated in metastatic tumors by longitudinal pair-wise comparisons between primary-to-metastatic tumors and 2) to understand tropism between colon-to-liver and colon-to-lung metastases at gene expression level. Methods: Total 24 tumor samples were prepared as longitudinal pairs from 6 hepatic, and 6 pulmonary cases. In these samples mRNA levels were quantitatively determined for 215 genes that were previously reported to play roles in metastasis, cytokines signaling, or angiogenesis, as provided as RT2 Profiler TM PCR arrays (PAHS-022, 024, 028). Unsupervised hierarchical clustering of Ct values and heat map analyses of DCt values were carried out using web based data analysis program, and 17-gene tropism signature was selected for stratification of the hepatic and the pulmonary metastases. Results: Ct values of 23 duplicated genes and 5 house-keeping genes showed plate-to-plate correlation of 0.92. Unsupervised hierarchical clustering of the Ct values from the Metastasis Arrays revealed that the hepatic metastases were indistinguishable from the primary colorectal cancers (n=5/6), but the lung metastases were highly diversified (n=6/6). Cytokine Array data also showed the divergence of pulmonary metastases from the primary colorectal cancers (n=6/6). Heat map analyses of DCt values from the Metastasis Arrays identified 17-gene tropism signature that was sufficient not only to distinguish the liver and the lung metastases, but also reconstitute the clustering of primary tumors with the hepatic metastases. Conclusions: Intrinsic difference existed between the pulmonary and hepatic metastases of colorectal origins among the tested samples. 17-gene tropism signature was identified, and further genomic and clinical studies are in process to validate their potentials as therapeutic targets to treat pulmonary metastases of colorectal cancers.
Plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy.
Authors: Stoetzer Oliver J. , Stefan Holdenrieder , Lehner Julia , Fersching Deborah , Salat Christoph 
Published: March 2020

e21067 Background: In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting the response to the therapy are highly needed. Methods: Concentrations of ALU115, ALU247 and DNA integrity were analyzed in prospectively collected plasma of 68 patients with localized breast cancer (UICC II and III), of 47 patients with metastatic breast cancer and 28 healthy women as controls. In all 68 patients with breast cancer who had completed the course of chemotherapy until surgery, DNA and tumor biomarkers CEA and CA 15-3 were evaluated concerning response to therapy (no change, NC: N=18; partial remission, PR: N=35; complete remission, CR: 15). Results: Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with localized (medians 16.3 and 16.8 ng/mL) and metastasized breast cancer (22.2 and 29.8 ng/mL) than in healthy controls (1.8 and 1.9 ng/mL). However, plasma DNA integrity showed no significant differences between the diagnostic groups. AUCs in ROC curves for discrimination of localized breast cancer from healthy controls were 96% for ALU 115 and ALU 247, respectively, and 60% for DNA integrity. Concerning therapy response, pretherapeutic ALU 115, 247, and DNA integrity and also CEA and CA 15-3 were not significantly different when patients with and without remission (CR vs PR+NC and CR+PR vs NC) were compared. Conclusions: While plasma DNA levels are valuable for discrimination of breast cancer patients from controls, pretherapeutic DNA integrity provides no additive diagnostic information nor indicates response to neoadjuvant therapy.
Effect of cancer patients’ oxygen breathing during uptake phase of the study on tumor F18-FDG uptake.
Authors: Li Xiao-Feng , Kloecker Goetz H. , Sharma Vivek R. , Bhatt Geetika , Bhatt Aashish D. , Civelek Ali Cahid 
Published: March 2020

e21072 Background: We previously reported that in mice, 18F-FDG uptake is higher in hypoxic cancer cells than well-oxygenated xenografts of human cancer cells. This enhanced uptake was abrogated by carbogen (95% O2 +5% CO2) breathing. We hypothesized that in clinical applications, oxygen breathing of the patients’ during the uptake phase may blunt the 18F-FDG uptake of the tumor and the liver. Methods: Overnight fasted patients with blood glucose level < 200 mg/dl were injected with < 14.0 mCi of 18F-FDG, and PET/CT scans were performed at 60 -80 minutes later with a Siemens PET/CT scanner. Group-1 is consisted of 11 patients who were breathing room air only, without any additional oxygen during the procedure. Group-II consisted of 12 patients who were breathing oxygen during the uptake phase. Group-III consisted of 10 patients who were breathing oxygen only at the time of scanning and not during uptake phase. Tumor FDG activities of the groups were not compared since no paired data (with and without oxygen in same patient) was available. Thus, Liver FDG activity of the patients in each group were measured as surrogate to the oxygen effect on tumor, and expressed as Liver SUV max and Liver SUV average values, and they were compared to each other to determine the statistical significance. Results: Both liver SUV max and SUV average values were significantly lower in Group-II patients who were breathing oxygen during the uptake phase compared to Group–I and Group-III (P< 0.05 for both). Liver SUV max and SUV average values were not significantly different between Group–I and Group–III. In one patient who had a paired scans with and without O2 during the uptake phase showed a significant FDG activity of the tumor when he was breathing O2 during uptake phase. Conclusions: In cancer patients, O2 breathing during FDG uptake phase may significantly blunt 18F-FDG uptake, thus, in cancer patients this may decrease the accuracy of the FDG PET/CT for the detection, staging of the disease and the assessment of the therapy effect. [Table: see text]
Association of serum CCL2 with advanced stage, metastasis, and smoking history in non-small cell lung cancer patients.
Authors: Ferreira Ana Carolina , Cordeiro De Lima Vladmir Claudio , Chinen Ludmilla Thome , Haddad Fabio Jose 
Published: March 2020

e21073 Background: Chronic exposition of respiratory tract epithelium to tobacco smoke triggers various inflammatory responses that participate in lung cancer initiation and promotion. CCL2, a CC chemokine, has been described to be involved in the lung inflammation associated with tobacco smoke exposure, and to play an important role in tumor progression and metastasis development in many solid malignancies. Methods: We prospectivelly collected blood from 165 individuals distributed in five groups: control/never smokers (64), former smokers (19), smokers (26), early stage NSCLC patients (9) and advanced stage (46). Former smokers must have stopped smoking for longer than 1 year. NSCLC diagnosis must have been confirmed histologically. Patients could not have been submitted to surgery, chemotherapy or radiotherapy, neither could have been taking corticoids, antibiotics or anticoagulants. 10ml of blood were drawn by peripheral vein puncture, using a dry Vacuntainer tube, which was kept at 37°C for 30' in a water bath. The serum was separated by centrifugation at 2000rpm, at 4°C, for 10 min., and frozen at 80°C. CCL2 was measured using a commercially available sandwich ELISA kit (Human CCL2 DuoSet kit, R&D Systems). Median concentration of CCL2 was compared among groups using Kruskal-Wallis test, followed by a Dunn’s test. Smoking burden and serum CCL2 concentration was correlated using Spearman’s test. Median CCL2 concentration in groups associated with each clinical-demographic variable was compared using Mann-Whitney or Kruskal-Wallis test. We assumed a p value <.05 to be statistically significant. Results: Serum CCL2 concentration was significantly higher in the advanced NSCLC group in comparison to the control group (p<.05) and the former smokers group (p<.05). Higher CCL2 levels were associated with having cancer (p=.002), metastasis (p=.025) and advanced stage disease (p=.029). No association was observed with smoking history and no correlation was observed between CCL2 level and smoking burden. Conclusions: Higher CCL2 level is associated with having NSCLC, advanced stage disease and metastasis. CCL2 concentration is not associated with smoking history or smoking burden.
Quantitative immunohistochemical (IHC) assessment of ataxia-telangiectasia mutated (ATM) in estrogen receptor (ER) negative early breast cancer (BC).
Authors: Tang Patricia , Klimowicz Alexander C. , Pond Gregory Russell , Heng Daniel Yick Chin , Webster Marc A. , Magliocco Anthony M. , Bebb D. Gwyn 
Published: March 2020

e21083 Background: ATM plays a key role in the cellular response to DNA damage and germline mutations are associated with a predisposition to BC. We evaluated the impact of ATM expression on outcomes in Stage I-III ER negative BC patients (pts). Methods: A tissue microarray was constructed from formalin-fixed paraffin-embedded specimens of ER negative Stage I-III BC pts from the Tom Baker Cancer Centre. ATM expression was assessed by quantitative fluorescence IHC using a rabbit anti-ATM monoclonal antibody (Epitomics) and the HistoRx AQUA platform. ATM expression index (EI) was calculated by the tumor cell to stroma expression ratio. Prognostic ability of ATM EI was explored univariately, and multivariately after adjusting for clinicopathological factors selected using algorithmic methods, with Cox regression methods. Results: Of 126 eligible pts treated from 1999-2004, 44.4% were HER2-neu + and 52.4% were triple negative. ATM EI was normalized using a logarithmic transformation. Univariately, higher ATM EI was associated with worse outcomes (Table). Multivariately, higher ATM EI remained significantly prognostic for recurrence-free survival (RFS) (HR=5.46, p=0.046), local RFS (HR=5.56, p=0.052), distant RFS (HR=4.38, p=0.080), but not overall survival (p=0.48). Conclusions: High ATM EI is associated with worse RFS in ER negative BC in this hypothesis-generating study. Validation of this finding is currently ongoing. [Table: see text]
Dissecting the link between nanoparticle lung effects and tumor markers with CD24 measurements.
Authors: Saeed Anwaar Mohammed , Alkhazna Ammar Ali , Molteni Agostino , Quinn Tim , Herndon Betty 
Published: March 2020

e21085 Background: It was postulated that carbon nanoparticles (CN) induced mesothelioma-like changes equal to asbestos in mice. We investigated CN added to human mesothelial cells in culture and reported that CN-induced cell damage to untransformed human mesothelial cells is rapidly followed by secretion of tumor markers like mesothelin and osteopontin. In vivo in animals, our group quantifies CN lung damage by HMGB1, an intranuclear protein released into alveolar lavage after CN exposure. Recent work suggests that the cell surface marker CD24 associates with HMGB1 to blunt lung responses to damage (like CN), but does not blunt cell response to pathogen-released HMGB1. Since CD24 is also a known cancer marker, elevated in many malignancies, we hypothesized that the cellular change elicited by CD24 when coupled with a damage marker would offer a mechanism through which CN could produce –repeated over time—malignant change in exposed human mesothelial cells. Such expression would support our previous research efforts. Methods: Untransformed human mesothelial cells were cultured and then stimulated or not with a CN dose giving 80% cell viability. At 24, 48 & 72 hr cells were fixed and stained with anti-CD 24. Presence of positive stain was photographed and counted. CN exposed and control rat lungs were harvested and frozen at 0.5 hr, 3 hr, 24 hr and 4 weeks. Western blot and immunostaining (with Anti-CD24 antibody and mucin chemical stain) was used to measure CD24 levels. Results: In CN-exposed animals, CD24 was highest at 24 hr. Mucin presence confirms the CD24 staining. Homogenates by Western blot also showed highest CD24 reactivity at 24 hr. In CN-exposed cultured cells, at 48 hr, some anti-CD24 staining was seen and at 72 hr in clusters of hyperproliferating cells, strong CD24 stain was seen. Conclusions: Our data suggest, as shown by a second cellular marker CD24, that the mesothelin upregulation seen in our previous studies indicated a cellular change beyond necrosis. Nanoparticles at a dose producing 20% cell death induce this change in healthy human mesothelial cells in culture.