bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunophenotypic diversity and prognosis of adult T-cell leukemia/lymphoma
Authors: Carrasco A. , Beltran B. , Malaga J. , Ferrel G. , Rios H. , Castillo J. , Huamani J. , Rodriguez M. , Flores D. , Falcon S. 
Published: March 2020

17565 Background: Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATLL classification (BHJ 1991:79), includes four types: acute, lymphomatous, chronic and smouldering; recently a new clinical cutaneous type had been described (BJD 2005:152). Methods: We described our experienced previously (ASH 2005, abst. 4797). Herein we analyzed immunophenotypically our ATLL patient population by flow cytometry looking for aberrant phenotypes and their correlation with overall survival. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: From July 1997 to March 2005 our registry had 69 cases, 37 had flow pre-treatment: acute type (n = 31) and lymphomatous (n = 6). Over our 37 flow done we were able to analysis only 33. The incidence of the typical (CD4+/CD8-) phenotype, the double-negative (CD4-/CD8-), the double-positive (CD4+/CD8+), and the CD8 positive (CD4-/CD8+) phenotypes was 58%, 12%, 15%, and 12% respectively. The median overall survival (OS) for the 33 patients was 4.1 months (range: 0.5–46.1). The patients with typical phenotypes had a median OS of 4.1 months better than the patients with the double-negative phenotype whom median OS was 2.0 (range: 1.5–9.7) but not significant. Median OS in the double positive and the CD4-/CD8+ phenotype population were 15.2 and 4.8 months respectively with no significance Conclusions: ATLL has a diversity of immunophenotype, our data suggest that there is not any correlation with survival, major accrual will gave us a final conclusion. No significant financial relationships to disclose.
Higher persistency with i.v. bisphosphonates in patients with bone metastasis
Authors: Mangiapane S. , Hoer A. , Gothe H. , Barghout V. , Haeussler B. 
Published: March 2020

18623 Background: Patients with advanced cancer are at high risk for bone metastasis, leading to accelerated bone resorption and skeletal related events and a loss of autonomy. Bisphosphonates can reduce the risk of skeletal complications, provided that patients remain on therapy. The aim of our study was to compare the persistency rates of oral and intravenous (i.v.) bisphosphonate therapy regimes in patients with bone metastasis in a natural setting. Methods: Claims data from a German sickness fund (2002 to 2004) were used. Patients had ICD-10 diagnoses for bone metastasis, were receiving oral or i.v. bisphosphonates (exclusively with a specific approval for patients with bone metastasis) and could be followed-up at least 7 months after their index prescription. Persistency was defined as the continuous prescription refill without an interruption of longer than 30 days. Medication Possession Ratio (MPR) was calculated after 180 days of follow-up and Kaplan Meier curves were analyzed. Results: We identified 233 patients who met our inclusion criteria, 85.8 % getting i.v. and 14.2 % getting oral therapy regime (prescribed bisphosphonates: zoledronate (60.5 %), pamidronate (27.5 %), clodronate (18 %), ibandronate (13.7 %)). Most of them had breast cancer (46.4 %) or prostate cancer (31.8 %). By the end of 6 months, only 64.4 % of all patients on bisphosphonate therapy were defined to be compliant, as they had a MPR ≥ 0.8 (36.4 % of the oral group and 92 % of the i.v. group). Kaplan Meier curves for oral and i.v. bisphosphonate therapy regime differed significantly (p = 0.0012). Conclusions: Persistency rates with oral bisphosphonates are significantly lower than with i.v. bisphosphonates in patients with bone metastasis (36.4 % vs. 92 %). Given the importance of preventing skeletal complications, persistency must be considered when selecting the optimum treatment regime for patients with advanced cancers. [Table: see text]
Analysis of five-year survival rate in patients with proximal femoral tumours after total hip replacement
Authors: Saravanan S. A. , Sokolovski V. , Voloshin V. , Aliev M. , Zybikov V. , Nisichenko D. 
Published: March 2020

19508 Background: To analyse the five-year survival rate in patients with proximal femoral tumours after total hip replacement. Methods: Between the period of 1994–2003, 50 patients were operated (Total Hip Replacement) for proximal femoral tumours at the Department of General Oncology (Bone & Soft tissue tuomurs), N. N. Blokhin Cancer Research Institute & Moscow Regional Clinical Research Institute, Moscow, Russian Federation. The histological diagnoses included 14 - metastases, 10 - osteosarcoma, 8 - chondrosarcoma, 4 - Ewing’s sarcoma, 4 - Giant cell tumor, 3 - malignant fibrous histiocytoma, 2 paraosteal and 2 periosteal osteosarcoma, and 1 each from primary neuroectodermal tumor, myeloid disease, and aneurysmal bone cyst. The follow-up ranged from 1–9 years (mean follow-up 5 years). 21 patients (45.7%) had pathological fracture. The cause of the pathological fracture was metastasis in 12 patients (26%). 28 patients (60.8%), had soft tissue invasion. All the survival analyses were done using Kaplan-Meier survivorship analysis method. Functional outcome was estimated using Enneking’s evaluation criteria. Results: The overall survival rate of patients was 66.7% at 5 years. 2 patients had local recurrence.12 patients had metastases after surgery. In that 11 patients were died. There was no evidence of disease in 32 patients. In 3 patients, we performed disarticulation of the hip joint because of the local recurrence. The overall survival rate of limb was 92.7% at 5 years. The overall survival rate of prostheses was 84.2% at 5 years. At the latest follow up, functional outcome was excellent in 15 (30%) patients, good in 27 (54%) patients, fair in 5 (10%) patients, poor in 3 (6%) patients. Conclusions: Though the extent of the muscle and bone resection is large, there is no doubt that endoprosthetic replacement of the proximal femur provides a good functional and oncological outcome when compared with the various other reconstructive surgeries. No significant financial relationships to disclose.
Evaluation of HER-2 expression in breast cancer using image analysis incorporating automatic feature recognition
Authors: Murray C. , Maddison J. , Anderson C. , Challender D. , Palmer S. , Rodgers J. 
Published: March 2020

20007 The currently favoured method for evaluation of HER-2 in routine clinical practice and research studies is immunohistochemistry (IHC). As standardised scoring of protein expression, using a scale of 0 - 3+, generates a significant number of false positives, fluorescent in situ hybridisation (FISH) is used to confirm the presence of gene amplification. Both techniques are laborious, and in the case of by-eye scoring of IHC, semi-quantitative at best. We have developed a high-throughput platform for the quantitative analysis of immunostained slides, based on fast, high-resolution scanning followed by analysis of digitised images (IA) using proprietary software, and in this study compared results obtained using this platform with those obtained using conventional methods. Archival sections of primary breast cancers collected at Nottingham City Hospital in 2004 and 2005 were stained for HER-2 (Herceptest, Dako), and evaluated by eye. Equal numbers of slides from scoring categories 0–3+ were then selected for further image analysis. The digitised images were subjected to automatic delineation to define areas of tumour parenchyma, and these areas further analysed using colour segmentation. Between 100 and 2000 fields were quantified on each section. Staining was expressed as a product of field fraction of coloured pixels and optical density. The results of IA demonstrate a continuum of staining values over the four conventional by-eye categories, with a non-linear correlation to by-eye scores. Inter-sample variation was greatest in the 3+ category, although the mean was much higher than that of the 2+ samples. The 2+ samples showed some variation, with several values not rising above baseline. To further investigate the relationship between FISH scores and IA results in the 2+ category, we analysed an additional set of slides in this group, and found a correlation between FISH and automated IA scores. We conclude that automated image analysis is sensitive to small differences in protein expression, has a wide dynamic range, and provides data superior to conventional by-eye scoring. In undecided cases HER-2 protein expression correlates with FISH data; therefore ultimately IA of HER-2 protein expression alone may provide a basis for clinical decisions. [Table: see text]
Tissue-dependent and tissue-independent gene expression changes in metastatic colon cancer
Authors: Shen P. , Hellmann G. M. , Gmeiner W. H. 
Published: March 2020

20014 Background: Changes in gene expression that occur during cellular transformation and establishment of metastases provide valuable information that may help determine prognosis and direct treatment. We have obtained gene expression profiles from primary colon tumors and metastases to the liver (V), lung (L), and peritoneum (P). Methods: Ten cases, with matched controls, were profiled for the expression of >18,000 human transcripts using Affymetrix U133A chips. Data were filtered using GeneSifter analysis software to identify genes with 2-fold or greater differences in expression relative to the control group. Gene expression levels for primary colon samples were compared to normal colon while metastatic tissues were compared to primary colon samples. Differentially regulated genes were then associated with KEGG pathways for additional analysis. Results: Relative to normal colon samples, primary colon samples displayed high positive z-score values for genes involved in nitrogen and sulfur metabolism (7.30 and 8.10, respectively). Expression level changes for individual genes in each cluster were statistically significant (e.g. p = 0.014 for carbonic anhydrase I in the nitrogen metabolism cluster). Metastatic tissue from liver, lung and peritoneum all displayed substantially decreased expression for genes involved in butanoate and propanoate metabolism, valine, leucine and isoleucine degradation, and moderately decreased expression for genes involved in JAK-STAT signaling. For example, L-3-hydroxyacyl-Coenzyme A dehydrogenase (short chain), a gene involved in both butanoate metabolism and valine, leucine and isoleucine degradation, was down-regulated in tissue from all three metastatic sites relative to primary colon tumor tissue [p = 0.024 (V), p = 0.022 (L), p = 0.005 (P)]. In addition, genes involved in phosphatidylinositol signaling were down-regulated in liver metastases but not in lung or peritoneal metastatic tissue. Conclusions: These results demonstrate that changes in expression levels for genes involved in basic metabolism and cell signaling occur during the course of metastasis. The changes that occur during development of the metastatic phenotype can be independent of, or specific to, the site of metastasis. No significant financial relationships to disclose.
Epidermal growth factor receptor (EGFR) status in different stages of resected non-small cell lung cancer (NSCLC): Implications for treatment with EGFR-targeted monoclonal antibodies
Authors: Berardi R. , Scartozzi M. , Squadroni M. , Santinelli A. , Brunelli A. , Gasparini S. , Valeri G. , Marmorale C. , Fianchini A. , Cascinu S. 
Published: March 2020

20015 Background: Aim of our study was to verify potential changes in EGFR status in different stages of resected NSCLC. This was done in order to find out whether assessing the EGFR status could be considered an effective tool for planning therapy with EGFR-targeted monoclonal antibodies in different setting of patients. Methods: From January 1996 through December 2001, 439 patients underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche. EGFR expression was evaluated with an immunohistochemical technique on five micron-thick tissue sections obtained from specimens fixed in 10% (v/v) neutral buffered formalin and paraffin embedded.EGFR expression was detected as membranous and/or cytoplasmic brown staining of neoplastic cells with various intensity. Positivity for EGFR expression was defined as any membrane staining above background level. Both the primary and metastatic neoplasm were considered positive when ≥ 1% of the tumour cells had membranous staining. Results: Table 1 summarizes patients’ characteristics. Samples from 423 patients were available for EGFR analysis. EGFR immunohistochemical expression was found positive as follows: 15.8% in stage IIIB, 12.2% in IIIA, 2.3% in IIB, 5.3% in IIA, 4.8% in IB and 5% in IA. At multivariate analysis, EGFR status resulted indicator of prognosis both when considering all the patients and in the groups of patients with different stages of disease. Conclusions: Globally our findings seem to confirm the role of EGFR as a prognostic indicator in NSCLC. Furthermore the observation that EGFR is more frequently overexpressed in the advanced stages may suggest that EGFR-targeted treatment strategies could be more appropriated in this subgroup of patients. [Table: see text] No significant financial relationships to disclose.
Investigation of estrogen receptor α phosphorylation in breast cancer
Authors: Sarwar N. , Jiang J. , Shousha S. , Coombes R. C. , Ali S. 
Published: March 2020

20046 Background: Estrogen receptor α (ERα) is an important predictive marker for response to endocrine therapy in breast cancer. Phosphorylation of ERα, in particular on serine 118 (S118), can result in ligand independent activation, thereby possibly contributing to resistance to endocrine therapies. The clinical significance of ERα phosphorylated at serine 118 (P-S118) in breast cancer was examined. Methods: Immunohistochemistry was performed on 301 primary breast tumor biopsies and on a small subset that had become resistant to endocrine therapy. P-S118 levels were scored using the modified McCarty’s H scoring system. Results: 282 (94%) of the 301 tumors were ERα positive. Of the 282 ERα positive patients, 282 (83%) had detectable nuclear staining for P-S118. There was no association between P-S118 staining and tumor size, nodal status, progesterone receptor and c-erbB2 status. There was however a positive correlation of P-S118 with ERα expression, (p < 0.001) and activated (phosphorylated) mitogen-activated protein kinase (MAPK) expression (p < 0.001). There was a clear inverse relationship with tumor grade and P-S118 staining (p < 0.001). Lower grade tumors being associated with higher H-scores for P-S118 staining. There was also some evidence of an association between P-S118 and age (P = 0.08). No association was found between P-S118 expression and survival. There was however a statistically significant difference in the distribution of P-S118 expression before and after becoming resistant to hormonal therapies (z = −2.357 p-value = 0.02). Comparison of H-scores showed that P-S118 levels were elevated following tumor regrowth. Conclusion: This analysis shows that S118 phosphorylation is higher in more differentiated tumors, suggesting that phosphorylation at this site is associated with a better prognosis. However, S118 phosphorylation is elevated in biopsies taken from patients who had relapsed on tamoxifen, compared to pre-treatment biopsies. Collectively these data indicate a complex role for ERα phosphorylation at least at S118, in breast cancer progression. No significant financial relationships to disclose.
Prognostic significance of leptin (L) and leptin receptor (OB-R) expression in human breast cancer (BC)
Authors: Kulkarni S. , Saxena S. , Watroba N. , Groth J. , Brady W. , Edge S. , Geradts J. 
Published: March 2020

20054 Background: L is a cytokine-like hormone that controls adipocyte mass and energy balance by binding to OB-R. Both L and OB-R have been implicated in carcinogenesis and were recently identified in human BC. The clinical significance of increased expression of L and OB-R in human BC is unclear. Methods: The anti-L rabbit (A-20) and anti-OB-R goat (M-18) polyclonal antibodies (ABs) from Santa Cruz Biotechnology were applied in indirect immunohistochemical (IHC) assays. Following antigen retrieval, ABs were reacted with 5 μm paraffin sections of tissue microarrays (TMAs). TMAs included 1mm cores of 316 women with operable BC and contained invasive cancer (IC), ductal carcinoma insitu (DCIS), surrounding histologically normal tissue (N) and nodal metastases (M). For L, nuclear (LN) and cytoplasmic (LC) staining were evaluated separately. For OB-R, one qualitative score (0, +1, +2, +3) was applied to each case. For analysis, 0, +1 were considered low and +2, +3 were considered high expression. Expression of LN, LC, and OB-R were evaluated with respect to clinicopathologic variables; disease free survival (DFS) and survival (S) were evaluated using Cox regression. Results: Median S and DFS were 11.4 and 10.1 years. Tissue from 113 patients with IC, 93 patients with N, 49 patients with M, and 36 patients with DCIS were evaluable for LC, LN and OB-R. OB-R expression was significantly higher in lobular vs. ductal carcinomas (p < .001). Increased expression of LC, LN, or OB-R was not associated with aggressive pathologic features studied in IC and DCIS. On multivariate analysis, highest expression of LN (+3) in IC was significantly associated with poor survival, p = .038, HR 3.51 (1.07–11.51 95% CI). Strong expression of LN in N was also associated with decreased survival, p = .043, HR 8.43 (1.07, 66.30 95% CI). Strong expression of OB-R expression in N was significantly associated with increased DFS and S, p = .004, HR 0.21 (.07–0.61 95% CI) and p = .007, HR .29 (.11–.71 95% CI). Conclusions: In this limited study, LN appears to have a negative impact on survival in women with invasive BC when elevated in IC and N. Elevated levels of LR appear to have a protective effect when elevated in N. Larger studies are needed to confirm our findings and elucidate the mechanisms responsible for these observations. No significant financial relationships to disclose.
Impact of preoperative CEA levels on the prediction of lymphnode (LN) metastasis
Authors: Danno K. , Sugimoto T. , Ikeda M. , Ikeda K. , Ohnishi T. , Fukunaga M. , Ohta H. , Mishima H. , Watase M. , Sekimoto M. , Monden M. 
Published: March 2020

20070 Background: Although CEA is the most commonly used tumor marker for colorectal carcinoma (CRC) and it may correlate with poorer prognosis, data are insufficient to support its use to determine adjuvant therapy. Monitoring preoperative CEA might be useful if it would assist in staging and treatment planning. Methods: This study was a pooled data analysis of 1791 CRC patients (pts) collected prospectively from 25 hospitals participating in the MCSGO. The purpose of this study was to investigate the impact of preoperative CEA on the prediction of the number of LN metastasis (#LN). Data of 1328 pts were completed with preoperative CEA and clinicopathological (CP) data (number of dissected LN, #LN, tumor size, distant metastasis, macroscopic type, depth of invasion, histological type, and lymphatic and vessel invasion). Data of 582 pts with the number of dissected LN 12 were analyzed in this study. #LN was categorized in 5 levels (0, 1, 2, 3, and ≥4), and relationship between #LN and CEA was first investigated via a multivariate analysis based on adjusting for the other CP factors. Discrete logistic regression analysis was used, in which a random effect was incorporated to adjust some bias between hospitals. The linear effects for the factors were evaluated via the regression model. The multivariate adaptive regression spline (MARS), the most powerful tool in the statistical prediction, was employed for the prediction of #LN. Results: The effect of the CEA adjusted by the other CP factors had a positive trend with two-sided P-value of 0.0394 for #LN. The adjusted R-squared measure (R2*) by the MARS fitting, a prediction performance index of #LN, was 0.369, and that averaged based on Bootstrap sampling (Bagging method) was R2* = 0.405. The relative importance of each factor in the prediction of #LN estimated by the decrease rate of R2* on masking each factor is shown in the Table . The relative importance of CEA in the prediction of LN# was ranked second next to lymphatic invasion. Conclusions: Preoperative CEA has a significant impact on the prediction of #LN. [Table: see text] No significant financial relationships to disclose.
RELMb is a hypoxic induced mitogenic factor in human adenocarcinoma A549 celline
Authors: Rose F. , Renigunta A. , Grimminger F. , Seeger W. , Hänze J. 
Published: March 2020

20072 Background: RELMb (resistin-like molecule) represents the closest related human homologue of mouse RELMa, also known as hypoxic-induced-mitogenic-factor (HIMF). However, no orthologous gene of mouse HIMF exists in human. Results and Methods: In this study, we cloned human RELMb cDNA from lung and performed regulatory and functional expression studies in adenocarcinoma A549 cell line. RELMb mRNA was found to be strongly upregulated in hypoxia in these cells. Upon transfection of a RELMb encoding expression plasmid, we observed significant induction of proliferation in A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. Conclusions: The results suggest that human RELMb may contribute to hypoxic-induced proliferative responses in adenocarcinoma cells via PI3K dependent signal transduction. No significant financial relationships to disclose.