bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study to compare 8 - FDG and F18 PET/CT study in delineating metastases in suspected skeletal disease
Authors: Shah S. A. , Rangarajan V. , Purandare N. C. , Sharma A. R. , Arora A. C. , Parasar D. S. 
Published: August 2020

e22052 Title: A pilot study to compare the 18 - FDG and F18 PET/CT study in delineating metastases in suspected skeletal disease. Background: Flourodeoxy glucose (FDG), positron emission tomography/computed tomography (PET/CT) scans have been used to identify metastatic disease including skeletal lesions. But the advent of Flourine -18 (F - 18), has necessitated a need to identify its accuracy over FDG scans. Aim: To evaluate and compare FDG PET/CT and F18 PET/CT studies in locating skeletal metastases in patients with suspected disease. Methods: A pilot study was carried out on 27 patients who were referred for a FDG PET/CT study for suspected skeletal disease. A whole body (skull to ankle) FDG PET/CT study followed by a F18 PET/CT bone scan within a period of 1 week was performed. A total of 150 lesions with increased tracer concentration on FDG and F18 scan were analyzed and the characteristics of the lesion on corresponding CT images were noted. Results: Of the 150 lesions noted, 49 were seen in both FDG and F18 scans. 11 were sclerotic,16 lytic, 17 mixed while CT was normal in 5 lesion. 95 of the 101 mismatched lesions were seen on F18 scan alone & were not appreciated on the FDG scan. 40% were sclerotic, 12% mixed and 11.5% were lytic. Degenerative changes comprised 12% lesions. Only 6 mismatched lesions were seen on FDG and not appreciated on F18 study.They showed no morphological abnormality on CT. 9 patients with a negative FDG scan showed lesions ranging from solitary to 16 on F18 scan, while 5 patients who had a single metastasis on FDG showed more than 6 lesions on a F18 scan. Conclusions: A F18 PET/CT study detects more skeletal lesions than FDG PET and can thus has a potential to impact patient management . Sclerotic lesions missed on FDG scans seem to be better picked on F18 scans. This pilot study provides the feasibility of a prospective study in a larger patient population to validate the impact of F18 scan in identifying skeletal metastases in various malignancies with a predisposition to bone spread. No significant financial relationships to disclose.
Underweight and breast cancer recurrence and death
Authors: Moon H. , Han W. , Lee J. , Ko E. , Kim E. , Kim E. , Yu J. , Noh D. 
Published: August 2020

e22054 Background: The association of body mass index or body weight and breast cancer outcome is controversial. Furthermore, the impact of underweight on breast cancer recurrence and death has not been adequately addressed. Methods: We investigated this issue in a large nation-wide database of 14,039 Korean breast cancer patients (Korean Breast Cancer Registry). Furthermore, to test whether the association was due to more frequent non-cancer death in underweight women, we used breast cancer recurrence data of 4,345 women from single institution (Seoul National University Hospital). Results: The results from Korean Breast Cancer Registry data showed significantly lower overall survival in underweight patients compared to normal weight after adjusting known prognostic factors [hazard ratio=1.36 (95% CI 1.08–1.72)], which was not observed in obese patients. The association between body mass index and breast cancer recurrence was further investigated in Seoul National University Hospital data. Underweight women had significantly higher risk of distant metastasis and local recurrence of breast cancer [hazard ratio=1.86 (95% CI 1.25–2.76) and 2.62 (95% CI 1.55–4.41), respectively]. Conclusions: These findings suggest that underweight could be considered as high risk factor of death and recurrence after breast cancer surgery. No significant financial relationships to disclose.
Pattern of relapse and the risk of second malignancies in molecular subtypes of early breast cancer (BC)
Authors: Radecka B. , Hudala-Klecha J. , Badzio A. , Szwiec M. , Drosik K. , Jassem J. 
Published: August 2020

e22057 Background: In a large, consecutive series of early BC patients (pts) we investigated clinical behavior of four major molecular subtypes, with particular focus on pattern of relapse and the risk of second malignancies. Methods: BC cases were divided into four phenotypes: triple negative BC (TNBC), characterized by negativity of hormone receptors (HR) and HER2 (0–2+ by immunohistochemistry), HR+/HER2-, HR+ /HER2+ and HR-/HER2+. All pts underwent curative surgery between January 2003 and December 2007, followed by radiation and/or systemic therapy according to current standards. Univariate risks of relapse and death were estimated using Kaplan-Meier survival curves and compared with log-rank test, and the multivariate analysis used stratified Cox model. Results: Of the 783 tumors, 520, 50, 48 and 165 were classified as HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC, respectively. The TNBC and HR-/HER2+ subtypes were associated with higher tumor grade (p<0.001), higher T stage (p<0.001), and higher proportion of medullary type (p<0.001) compared to other two subtypes. After a median follow-up of 30 months, the risk of relapse in HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC was 5.0%, 10.0%, 12.5% and 12.1%, respectively (p=0.007). Inferior prognosis of TNBC and HR-/HER2+ types remained significant after correction by T and N stage. Of the 57 relapses, 12 were locoregional, 37 distant and 8 concomitantly locoregional and distant. In TNBC isolated locoregional relapse constituted 45% of all relapses, compared to 8.1% in three other subtypes combined (p=0.001). TNBC was associated with almost doubled risk of second malignancy compared to all other types combined (12.7% vs. 6.5%, respectively; p=0.008). This risk was significantly increased for contralateral BC and endometrial cancer (p=0.002 and 0.024, respectively). Conclusions: Poor prognosis of TNBC is related to increased occurrence of both locoregional and distant relapses. Additionally, this subtype carries increased risk of second malignancies, most likely due to higher proportion of hereditary BC. No significant financial relationships to disclose.
The antitumor effect of orally active heat shock protein 90 Inhibitor, 17-DMAG, on the growth of gefitinib-resistant non-small cell lung cancer
Authors: Kubo T. , Kobayashi N. , Jida M. , Hayashi T. , Yamamoto H. , Otani H. , Kiura K. , Sano Y. , Toyooka S. 
Published: August 2020

e22064 Background: It has been reported that NSCLC cell lines with activating mutations of EGFRgene were significantly sensitive to Heat Shock Protein 90 (Hsp 90 ) ihibitors regardless of the secondary T790M mutation. Methods: We examined the antitumor effect of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), the orally active Hsp90 inhibitor, on the growth of NSCLC cell lines in vitro and in vivo. Results: In MTS assay, the IC50 values for 3 cell lines with EGFR mutation (PC-9, RPC-9, and NCI-H1975) ranged from 0.15 to 0.28 μM. RPC-9 is a gefitinib-resistant lung cancer cell line with the secondary T790M mutation established from PC-9. By contrast, those of 7 EGFR-wild type cell lines ranged from 1.63 to 28.5 μM. Western blot analysis revealed that mutant EGFRs were more readily depleted than wild-type EGFRs after the treatment of 17-DMAG. Furthermore, expression of phospho-Akt, phospho-MAPK, cdk4, and cyclin D1 was depleted after exposure to low concentrations of 17-DMAG in EGFR-mutant cells. Celeaved PARP expression confirmed apoptosis in response to 17-DMAG in EGFR-mutant cells. In animal models, 17-DMAG significantly reduced the growth of EGFR-mutant cell lines PC-9 and RPC-9 compared with controls and induced degradation of mutant EGFR. In contrast, 17-DMAG did not inhibit the growth of EGFR wild type cell lines compared with controls. Conclusions: These results suggested that 17-DMAG could become a novel therapeutic agent for patients with lung tumors expressing mutant EGFR and having developed clinical resistance to gefitinib. No significant financial relationships to disclose.
Immune self-tuning in renal cell carcinoma patients
Authors: Busse A. , Asemissen A. , Schmittel A. , Zimmermann K. , Miller K. , Rietz A. , Ochsenreither S. , Fusi A. , Thiel E. , Keilholz U. 
Published: August 2020

e22069 Background: Renal cell carcinoma (RCC) cells can inhibit protective antitumor immunity by secretion of immunosuppressive factors leading to the induction of regulatory T cells. The objective of this study was to investigate the prognostic impact of mRNA expression levels of IL10, TGFβ and forkhead box transcription factor (FoxP3) mRNA in peripheral blood mononuclear cells (PBMCs) of metastatic RCC patients before receiving treatment with sorafenib. Methods: PBMCs of 46 patients were assessed for their expression levels of TGFβ, IL10 and FoxP3 by quantitative RT-PCR. Clinical features considered included ECOG performance status, hemoglobin, alkaline phosphatase, and calcium concentrations. Disease evaluation was performed every 8 weeks following RECIST criteria. Relationship between pre-treatment factors and survival were examined in univariate analyses and subsequently by multivariate analysis using a stepwise Cox regression model. Results: In contrast to FoxP3, mRNA expression levels of IL10 and TGFβ were significantly higher in the 46 RCC patients compared to healthy volunteers: Median expression levels [ratio marker /housekeeping gene PBGD] were 5.56E-05 vs 2.05E-04 (P=0.034) for IL10 and 7.38E-02 vs 3.04E- 01 (P=0.023) for TGFβ. Univariate analysis revealed a negative prognostic influence of IL10 on progression free survival (p=0.04) and on overall survival, although not significant (P= 0.063). Surprisingly, high TGFβ and FoxP3 expression levels had a positive influence on progression free (P<0.001 and P=0.047, respectively) and overall survival (P<0.001 and P= 0.031, respectively). In the multivariate analysis low ECOG performance status and high TGFβ mRNA expression levels were independently associated with worse progression free (P=0.001 and P=0.054,) and worse overall survival (P=0. 006 and P< 0.001, respectively). Conclusions: RCC caused an immune-suppressive phenotype in PBMC characterized by increased mRNA expression levels of IL10 and TGFβ. Surprisingly, in contrast to IL10, a high TGFβ mRNA expression level was an independent good prognostic factor. Whether this observation can be attributed to recently described immune promoting functions of TGFβ needs to be determined. No significant financial relationships to disclose.
Investigation of infiltrating regulatory T lymphocytes in tumor areas in oral cancer lesions
Authors: Sukhotska I. , García-Alonso L. , Sirera R. , Sarrión G. , Jantus Lewintre E. , Gil M. , Cabrera A. , Berrocal A. , Bagán J. , Camps C. 
Published: August 2020

e22070 Background: HLA-G is a human non-classical MHC molecule, mainly expressed in the trophoblast whose main function is to suppress immunologic activity that allows maternal tolerance to phoetus. On the other hand, infiltrating regulatory T lymphocytes (Treg) could promote peripheral inmunotolerance fo oncogenic transformation. Methods: We performed real-time PCR in frozen oral cancer specimens from untreated patients who had undergone surgical resection (n=22) and in normal oral mucosa from healthy subjects (n=10). Samples were processed for mRNA extraction and quantification of gene expression was expressed as relative concentration by an endogenous gene. To asses the presence of infiltrating Treg we analysed CTLA-4, Foxp-3, IL-10, TGF-beta, CD4, CD8, CXCR4, CD127 and CD25 and also we determined HLA-G levels. We correlate the expression of immunologic mediators with clinical variables. Results: Patients presented squamous carcinomas of the tongue (n=12) or gum (n=10) and stages ranged from I to IV (stage I=4; II=9; III=4; IV=5). 10 patients presented well-differentiated lesions and the other 12 moderately-differentiated cells. Eight patients received post- surgery chemo and radiotherapy. Our results show that tumor samples had significant higher expression of the CTLA-4, Foxp-3, TGF-beta and CD127 genes than normal tissue. However, those data showed no correlation between the levels of expression and clinico-pathologic variables. When patients were grouped according to tumor size, there was a trend in the way that bigger tumoral lesions expressed relative higher amounts of Treg. By contrast we could not observe an increase of the expression of HLA-G in patients. Conclusions: Our results reveal that there is an increase in the expression of Treg in oral cancer patients. These Treg in tumoral tissues might contribute to the impairment of immunological rejection of the neoplasic transformation. Conversely we have not been able to demonstrate tumoral expression of HLA-G as a strategy to escape from immunosurveyance. Further analysis of this cells and their function is important in order to develop new therapeutic strategies. No significant financial relationships to disclose.
Plasma thermogram profiling: A novel biomarker for lung cancer
Authors: Xiang D. , Garbett N. C. , Chaires J. , Laber D. L. , Kloecker G. H. 
Published: August 2020

e22074 Background: Currently, there are no clinically useful biomarkers for lung cancer (LC). We developed a novel approach by using differential scanning calorimetry (DSC) to analyze the plasma proteome of LC patients. Our assay produces a signature snapshot of the plasma proteome based on the thermal properties of the constituent proteins within the mixture. Each individual protein has a unique and characteristic melting temperature and melting enthalpy. These biophysical properties are as intrinsic and unique for each protein as are its sequence, mass, and charge. The denaturation of plasma results in a composite signature thermogram that represents the sum of all of the individual proteins within the proteome, weighted according to their concentration within the plasma or serum. Our goal is to identify unique thermogram profiles as biomarkers for lung cancer evaluation. Methods: Plasma samples were collected from LC patients and healthy volunteers. Sample analysis was performed using an automated capillary DSC. Comparison of plasma thermograms from controls and diseased individuals was done using quantile-quantile plots and the Kolmogorov-Smirnov test. Results: One hundred samples were obtained from healthy volunteers. DSC thermograms from control plasma were highly reproducible and yielded a characteristic signature with a well-defined shape and temperature maxima. Twenty samples from LC patients were obtained at diagnosis. Plasma from LC individuals yielded a unique thermogram that differs from that of healthy controls. Preliminary results suggested that DSC was sensitive to properties of the plasma proteins other than their charge and mass. We hypothesize that changes in thermogram shapes and positions in LC can arise from changes in the concentrations of plasma proteins, from disease-induced protein-protein interactions, or from the secretion into plasma of disease-related peptides that can bind to the most abundant plasma proteins. Conclusions: Lung cancer may have a characteristic signature thermogram that may serve as a biomarker for LC; further studies are needed to elucidate the biophysical and molecular mechanisms of different thermograms between normal individuals versus those with disease or cancer. No significant financial relationships to disclose.
Effect of Notch inhibition on radiation in an explant model of glioblastoma multiforme
Authors: Hovinga K. E. , Wang R. , Shimizu F. , Moayedparadazi H. , Menon J. , Correia A. , Major T. , Tabar V. 
Published: August 2020

e22080 Background: Glioblastoma Multiforme (GBM) is highly radioresistant, possibly due to a subpopulation of Brain Tumor “Stem-like‘ Cells (BTSC) capable of repopulating the tumor. The Notch signaling pathway is essential for maintaining normal neural stem cells. We asked whether Notch inhibition can overcome radioresistance by allowing BTSCs to exit their stem cell state. Methods: To maintain the BTSCs in their original niche we used an organotypic culture method (explants). GBM explants are cultured on a semiporous membrane in an air-medium interface. They are treated with the Notch inhibitor DAPT, radiation or a combination thereof. Proliferation and neurosphere forming capacity are assessed. Results: The explant model faithfully maintained the cytoarchitecture of the tumor (preservation of blood vessels and pericytes) and its high proliferation rate (%ki67+ cells: 14.3% -17.1%). The effect of DAPT or radiation treatment alone differed among tumors (from no change to a two-fold and nine-fold decrease post DAPT or radiation respectively). However, in all tumors tested the combination of DAPT and radiation dramatically decreased the proliferation rate compared to either treatment alone (%ki67 + cells: 0.19%-2.24%). Interestingly the rate of neurosphere formation was highest following radiation alone (threefold increase). Neurosphere formation after DAPT treatment differed amongst the tumors from a decrease (fourfold) to an increase (twofold). The combination treatment resulted in a modest increase over control (twofold). Conclusions: Our data demonstrates that inhibition of proliferation does not correlate with the status of neurosphere forming ability, arguably a surrogate for cancer stem cell function. Combining radiation with notch inhibition has a profound effect on GBM proliferation, most likely due to selectively inhibiting the BTSC repopulating ability. Ongoing studies will determine the impact of this approach on tumor growth and progression in in vivo tumor models. No significant financial relationships to disclose.
False-positive diagnosis of breast cancer by diffused optical tomography with ultrasound
Authors: Wang X. , Li Y. , Cao X. 
Published: August 2020

e22085 Background: Breast cancer is one of the most common cancer in women. Early detection, early diagnosis and early treatment play key role in fighting against breast cancer. OPTIMUS system is a system of diffused optical tomography with ultrasound. It provides dual modality images for early diagnosis of breast cancer. The aim of this study was to evaluate the OPTIMUS system on diagnosis of breast disease. Methods: OPTIMUS system was applied to 160 breast tumor patients. All patients had received surgical treatment and had definite pathological diagnosis. OPTIMUS system was evaluated as diagnostic tool of breast tumor in this study. Results: There were 42 cases diagnosed as benign breast disease and 118 cases diagnosed as breast cancer by OPTIMUS system. Pathology confirmed 60 cases of benign disease and 100 cases of breast cancer. False positive rate of breast cancer was 30% (18/60). False negative rate of breast cancer was 0% (0/100). The pathology of false positive cases was mild and severe papillomatosis (6/18), non-typical hyperplasia (4/18), chronic inflammation (3/18), fibroadenoma (3/18) and fat necrosis (2/18). Papillomatosis and non-typical hyperplasia are precancerous lesions and often difficult for clinical diagnosis. In this study the false positive diagnostic rate of mammography and ultrasonography is 13% and 11.1% respectively. Conclusions: OPTIMUS system is a non- invasive and highly effective diagnostic tool for breast disease. Its sensitivity is reached to 100% and specificity is about 70% on the diagnosis of breast cancer. OPTIMUS system could be used as assistant diagnostic tool for breast tumor. No significant financial relationships to disclose.
Use of novel optical proteomics to profile breast cancer patients leading to individualised prognosis and tailored treatment
Authors: Kelleher M. T. , Festy F. , Barber P. R. , Gillett C. , Ofo E. , Coolen A. , Pinder S. , Patel G. , Vojnovic B. , Ng T. , Ellis P. A. 
Published: August 2020

e22090 Background: Optical proteomics quantifies interactions between proteins and post-translational modifications by measuring Förster resonance energy transfer (FRET) quantified by fluorescence lifetime imaging microscopy (FLIM). This project aims to derive multiple high throughput optical proteomic markers, to predict metastatic risk at first diagnosis, and to perturb ‘high risk' protein-protein interactions using targeted therapeutics. This initial step develops robust FRET/FLIM assays, suitable for use in formalin fixed paraffin embedded (FFPE) tissue to be correlated with patient outcome. Methods: Fluorophore-conjugated antibodies to proteins involved in cell migration and survival, were applied to tissue microarrays (TMA), created from archived FFPE invasive ductal breast carcinoma samples. Where fluorophores are located within nanometer proximity, FRET occurs, thus allowing quantification of protein-protein interaction. Ezrin and PKCα phosphorylation, distribution, and interaction were imaged on four TMAs (patients diagnosed with early breast cancer 1984 -1987: 20 years follow-up data). Results: 71 patient samples were optically imaged. Patients were clustered based on the pairwise distances between 18 optical variables ‘input data'. Data are represented on self organising maps and dendrograms and correlated with clinical outcome ‘output data', displaying a heatmap distribution. Conclusions: Ezrin and PKCα phosphorylation, distribution, and interaction imaged optically within FFPE contain prognostic information regarding metastatic outcome in breast cancer, thus stepping ever closer to individualising prognosis. These advanced optics-based parameters informing on metastatic potential will be validated in prospective studies in conjunction with FRET/FLIM assays measuring HER2/HER3 dimerisation, and EGFR and HER2 ubiquitination in order to improve patient selection for targeted therapy. No significant financial relationships to disclose.