bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer incidence in HIV-positive patients in Germany: A nation-wide survey from 2000 to 2007
Authors: Hensel M. , Goetzenich A. , Hanhoff N. , Wolf E. , Knechten H. , Mosthaf F. 
Published: August 2020

e22115 Background: Malignancies are an essential feature of acquired immunodeficiency syndrome and human immunodeficiency virus (HIV) infection. The purpose of this study was to gather data on the epidemiology of AIDS-defining (AD) and non-AIDS-defining (NAD) malignancies in HIV-positive patients (pts) in Germany in the past decade. Methods: Study centers (all HIV-specialty clinics and ambulatory care centers in Germany, all members of the German association of medical oncologists in private practice) were contacted annually between 2000 and 2007 and asked to respond to a structured questionnaire. The questionnaire requested information on all malignancies in HIV-positive pts, tumor stage, CDC (Center for Disease Control)-stage of the HIV infection, sex, treatment and clinical course. Results: 111 centers participated in the evaluation and provided 552 evaluable data sets from 542 pts. 89% of cases were male. The majority of pts had advanced HIV-disease (CDC stage C3), but the proportion of pts with stage C3 decreased from 58% in 2000 to 36.8% in 2007. 253 (45.8%) were AD as follows: 132 Kaposi Sarcomas, 109 aggressive B-cell lymphomas, 12 invasive cervix carcinomas. The B-cell lymphomas further included 28 Burkitt's lymphomas, 30 DLBCL, 9 Castleman diseases, 8 primary cerebral lymphomas. Among the 299 cases (54.2%) of NAD malignomas were 213 solid tumors including 71 anal carcinomas (= 33.5% of all NAD malignancies) and 85 hemoblastoses including 29 Hodgkin lymphomas (= 9.6% of all NAD malignancies). The high proportion of NAD malignancies has remained constant over all observation periods, as well as the relative incidence of most of the different subentities. Interestingly, only 1 of 8 primary cerebral lymphomas has been reported after 2001. The number of pts with Hodgkin's lymphoma has increased constantly from 2000 to 2007. Conclusions: Our observations show a high incidence of NAD malignomas over the past 8 years in Germany. Anal carcinomas and Hodgkin's lymphomas in particular were markedly more prevalent in our HIV-positive cohort compared to published reports of the general population. The incidence of primary cerebral lymphomas seems to decrease, whereas the incidence of Hodgkin's lymphoma is increasing. No significant financial relationships to disclose.
Circulating tumor cell detection: A direct comparison between the CellSearch System, the AdnaTest, and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer
Authors: Dirix L. Y. , Elst H. , Benoy I. , Van der Auwera I. , Prové A. , Wuyts H. , Maes H. , van Dam P. , Huget P. , Vermeulen P. 
Published: August 2020

e22117 Background: The detection, enumeration and isolation of circulating tumor cells (CTC) has considerable potential to influence the clinical management of patients with breast cancer. There is however a substantial variability in the rates of positive samples using existing detection techniques. Methods: This study was designed to compare three techniques for detecting CTC in blood of 80 patients with metastatic breast cancer (MBC) and 20 healthy controls: the CellSearch System, which is an automated, standardized and regulatory-approved system for the immunocytochemical detection and quantification of CTC in blood; ii) the AdnaTest Breast Cancer Select/Detect, which involves the detection of tumor-associated transcripts by RT-PCR after an immunomagnetically enrichment of tumor cells; iii) an in-house developed multimarker qRT-PCR assay, which involves the quantification of tumor-associated transcripts (CK-19 and MAM) by qRT- PCR. Results: As a result, 23% of patients with MBC were positive by the CellSearch System (≥5 CTC), 22% by the AdnaTest (>0.30 ng/μl for any of the amplicons), 31% by qRT-PCR for CK-19 and 49% by qRT-PCR for MAM. Samples were more likely to be positive by qRT-PCR for at least one mRNA marker than by the CellSearch System (P<0.001) or the AdnaTest (P <0.001). The concordance between samples analyzed by the CellSearch System and the AdnaTest was substantial (κ = 0.667, P <0.001). Agreement between both detection techniques was observed in 88% of blood samples. When the CellSearch System was compared with the qRT-PCR assays for CK-19 and MAM, we observed agreement percentages of 78% and 58%, respectively (κ = 0.462, P <0.001 and κ = 0.159, P = 0.09). Agreement between the AdnaTest and the qRT-PCR assays for CK-19 and MAM was observed in 78% and 53% of blood samples, respectively (κ = 0.443, P <0.001 and κ = 0.05, P = 0.607). Conclusions: We observed a substantial variation in the detection rates of CTC in blood from MBC patients using three different techniques. A higher rate of positive samples was observed using a combined qRT-PCR approach for CK-19 and MAM, which suggests that this is currently the most sensitive technique for detecting CTC. No significant financial relationships to disclose.
Neuroendocrine tumors in children and young adults: Incidence, survival, and prevalence in the United States
Authors: O'Dorisio M. S. , Navalkele P. , O'Dorisio T. M. , Lynch C. F. 
Published: August 2020

e22120 Background: Neuroendocrine tumors (NET) arising from the diffuse endocrine system are thought to be quite rare in children and young adults. However, a surprising number of young people have been referred to our neuroendocrine tumor clinic and the NCI has targeted NET as a high priority for development of new diagnostic and therapeutic options. This analysis of the SEER database was undertaken to determine the incidence, prevalence, and survival of NET in young people. Their incidence, prevalence, and survival were compared with neuroblastoma, a related pediatric malignancy arising in the neural crest. Methods: The SEER data were obtained from 9 standard SEER registries for the diagnosis years of 1975 to 2004 using SEER*Stat version 6.4.4. ICD-9 codes related to neuroendocrine tumors and to neuroblastoma were characterized as to patient age, gender, racial and ethnic background, stage, grade, histology, incidence, survival, and prevalence. Results: Neuroendocrine tumors occur more often in females among children and young adults with the most common sites being bronchial, ovarian, and breast. The overall incidence of neuroendocrine tumors was lower than for neuroblastoma in the age range 0–30 years. However, the 30 year limited prevalence of neuroendocrine tumors in the 9 SEER registries was 698 compared to 881 for neuroblastoma. This extrapolated to over 7000 children and young adults with neuroendocrine tumors across the United States. Survival rate of young people with neuroendocrine tumors declined from 84% in 1975–1986 to 80% in the 1987–2004 era. Conclusions: These results indicate that neuroendocrine tumors constitute an unrecognized cancer threat to children and young adults. Survival of children and young adults with neuroendocrine tumors has decreased over the past 30 years in the United States. We recommend the establishment of centers of care for children and young adults diagnosed with neuroendocrine tumors with the expectation that earlier diagnosis coupled with targeted therapies will decrease the incidence of metastatic disease and improve survival. No significant financial relationships to disclose.
Relationship of systemic immune dysregulation in advanced tumors to vascular growth factor overproduction
Authors: Block M. S. , Markovic S. N. 
Published: August 2020

e22124 Background: Therapeutic anti-cancer vaccine strategies have been effective in a broad range of preclinical tumor models, but clinical trials of vaccines in metastatic cancer patients have failed to show clinical benefit. We have previously shown that patients with stage IV melanoma have systemic immunosuppression including elevated plasma levels of immunosuppressive cytokines and impaired DTH responses to recall antigens. Patients with stage IV melanoma also have elevated circulating levels of the vascular growth factors vascular endothelial growth factor A (VEGF A) and placental growth factor (PlGF). Based on these observations, we have hypothesized that vascular growth factors such as VEGF and PlGF mediate systemic immunosuppression. Methods: FVB mice with established ANV6 transplantable breast tumors were bled, and plasma samples were assayed for VEGF, PlGF, and interleukin (IL)-10. Splenocytes taken from tumor-bearing mice were stimulated via the T cell receptor (TCR), and interferon gamma (IFN) production was measured. Splenocytes from normal mice were stimulated in the presence or absence of VEGF; IFN production was measured. Results: Compared with age- and sex-matched controls, tumor-bearing mice had elevated plasma levels of VEGF, PlGF, and the immunosuppressive cytokine IL-10 (see table ). Furthermore, splenocytes from tumor-bearing mice produced less IFN upon TCR stimulation than did splenocytes from control mice. Finally, normal mouse splenocytes produced less IFN when stimulated in the presence of VEGF than in its absence (70.2 ± 37.2 vs. 260.0 ± 130.9 pg/ml). Conclusions: We have shown that mice with advanced tumors exhibit both elevated levels of vascular growth factors and systemic immune inhibition. We have also shown that VEGF leads to impairment of immune function in normal splenocytes. Taken together, these results suggest that excess vascular growth factors may mediate immunosuppression in animals with advanced tumors, which may in turn impair anti-tumor vaccine efficacy. [Table: see text] No significant financial relationships to disclose.
Are more genes better in clinical-genomic studies? A mathematical model to define identification power for clinically relevant genes
Authors: Crager M. R. , Shak S. 
Published: August 2020

e22136 Background: Modern molecular technologies that drive personalized medicine can generate expression data for thousands of candidate genes, or indeed, data for the “whole genome”. Clinical-genomic studies aim to identify genes that are truly associated with clinical outcome. We investigated the impact of large numbers of genes with little or no association with clinical outcome on the statistical power of studies to identify individual genes with strong association. Methods: We adapted Efron's (Ann Stat 2007) empirical Bayes approach to develop a method to calculate the identification power for individual genes in analyses that control the false discovery rate (FDR), the expected proportion of false positives. The identification power is the probability that a gene with a given true magnitude of association with clinical outcome will be identified when we control the FDR at a specified level. The identification power also depends on the proportion of genes studied that are not associated with outcome and the distribution of the degree of association among genes that are. Results: The identification power for clinically relevant genes decreases dramatically as the proportion of genes having no association with clinical outcome increases. For example, in a scenario in which 100 genes have some association with clinical outcome [median hazard ratio (HR) 1.125], increasing the number of genes having no association from 400 to 4000 decreases the identification power an individual gene having strong association (HR 1.42) from 80% to 36%. Similarly, when the number of genes having no association is 400 and the median HR among the 100 genes that have an association is decreased from 1.125 to 1.06, identification power for a gene with an association HR of 1.42 decreases from 80% to 62%. Conclusions: Identification power can be used to optimize strategies for gene finding and enable personalized medicine. Although technology allows the assay of ever-increasing numbers of genes, inclusion in a single study of many genes unrelated to clinical outcome is detrimental to the identification power for clinically relevant genes. Even with increased power, replication of results in independent studies will continue to be critically important. [Table: see text]
Selection of lung cancer-associated scFv antibodies from cultured cells
Authors: Massion P. P. , Pedchenko T. V. , Parekh D. V. , Mernaugh R. 
Published: August 2020

e22137 Background: Lung cancer is the most common cause of cancer-related deaths in the world. There is a critical need for new strategies of early lung cancer detection. The identification of tumor-associated antigens and corresponding antibodies is one approach to discovery of diagnostic biomarkers. We used a large phage-displayed recombinant antibody library and normal human lung epithelial and non-small cell lung cancer cell lines to select for and identify recombinant antibodies specific for proteins expressed, or over-expressed, in lung cancer. Methods: The antibody library was used to select for recombinant scFv antibodies reactive with proteins present, or aberrantly expressed, in non-small cell lung cancer cell lines (A549, H549, H157, H23) in comparison to normal lung cell lines (BEAS-2B, 16-HBE, KT). Soluble scFv antibodies were obtained through 2 rounds of phage antibody cross-absorption (on normal cell lines) and selection (on non-small lung cancer cell lines). Soluble scFv were assayed by a high-throughput fluorometric microvolume assay technology (FMAT) against normal and cancer lung cell line proteins. ScFv antibodies selected by FMAT were evaluated further with Western blot-based assays. Results: More than 100 scFv antibodies identified by FMAT bound preferentially to proteins in lung cancer. Of these, 46 scFv were assayed by a high throughput Western slot blot immunoassay against pooled normal lung and lung cancer cell lysates. Eight scFv were assayed in Western blot against individual lung normal and non-small lung cancer cell line lysates. Four of these demonstrated differential binding to normal and cancer cell lysates. Conclusions: In summary, we were able to detect cancer-associated antigens in lung cancer cell lines using a phage display antibody library. In combination with high-throughput fluorescent and Western blot assays, four unique scFv antibodies were selected that differentially bound to normal and lung cancer cell lysates. These scFv will be tested as candidate biomarkers of lung cancer in independent tissue and serum samples from patient with and without lung cancer to determine utility for use in lung cancer diagnosis. No significant financial relationships to disclose.
The oncologist as genetic consultant: Two-year results in a large community-based practice
Authors: Geier L. J. , Sheehan M. , Elia M. , Ethirajan S. , Kent E. 
Published: August 2020

e22140 Background: Oncologists are in a unique position to provide effective genetic cancer risk assessment (GCRA). However, in most communities they defer this to genetic counselors (GC). At KC Cancer Center, a 35-MD community oncology group, the difficulty obtaining timely and effective GCRA became a quality of care issue. Methods: In December 2006 a new program was launched with 4 designated oncologists providing GCRA at 4 separate cancer centers. Each oncologist was responsible for gaining expertise in the common hereditary syndromes and appropriate interpretation of gene testing results prior to starting GCRA. Two-year results were analyzed. For those pts found to have deleterious mutations, charts were reviewed to confirm the gene affected, and the length of time between cancer dx and GCRA. Pts more than one year out from dx were designated as cancer survivors. Results: After 2 years, 490 pts had gone through gene testing after GCRA, and 85 were found to carry deleterious mutations. These data were compared to the previous three years when pts had been referred to GC ( Table ). Both the number of pts tested and the number with mutations in yrs 2007–8 were approximately 400% of the numbers for yrs 2005–06. Of the 85 pts with mutations, 51 (60%) were cancer survivors. Their median time from diagnosis was 5.5 yrs (range 1–25). 75/85 (88%) mutations were in a BRCA gene. Conclusions: This oncologist-centered model proved to be very effective in identifying mutation carriers, particularly among cancer survivors in whom the hereditary syndrome had been previously overlooked. Acceptance of this approach by pts, physicians, and payers has been extremely high. This model should be considered by oncology practices wanting to add GCRA to their service lines. [Table: see text] [Table: see text]
Novel de novo BRCA1 mutation in a woman with early onset breast cancer
Authors: Tang E. , Kwong A. , Wong C. , Law F. , Wong C. , Ng E. , Ma E. , Ford J. M. 
Published: August 2020

e22143 Background: Germline mutations in BRCA1/2 account for a significant portion of hereditary breast/ovarian cancer. Mutation carriers usually have a family history of breast/ovarian cancer or early onset disease. Rarely, germline mutations are found only in the probands but not in any family members. Such de novo mutations have been reported in diseases such as hemophilia A, thalassaemia and familial adenomatous polyposis. De novo mutations in the BRCA1 or BRCA2 genes are rare and the few reported have been in BRCA2. Here, we describe de novo as well as novel mutation of the BRCA1 gene in a breast cancer patient. Methods: Blood DNA samples from a 30 year old Chinese woman with breast cancer and no family history of cancer was tested for a BRCA1/2 mutation by full gene sequencing and Multiple Ligation-dependent Probe Amplification (MLPA). Family members were analyzed for the same mutation. Paternity was determined by a set of highly polymorphic short tandem repeat (STR) markers. Results: Full gene sequencing found no deleterious mutation. MLPA revealed a large deletion of exons 1 to 12 of BRCA1 in the proband. MLPA performed on 5 family members: proband's mother and father (who were 1st degree relative- cousins), stepmother (mother's biological sister), 2 sisters (1, same parents; 1, same father and stepmother) found no similar deletion. By using a set of highly polymorphic STR markers, the proband's father and mother were confirmed to be her biological parents. Conclusions: We report a novel de novo BRCA1 deletion mutation encompassing exons 1 - 12 in a Chinese breast cancer patient of early onset with no family history. Identification of this large deletion confirms the importance of pursuing rearrangement testing if full gene sequencing fails to detect a point mutation or short insertion deletion. The mutation found in this study is de novo. This may simply be a random mutation event which occurred in the parents' germ cells during their lifetime which passed onto one of their offspring or maybe a result of gene inversion or splicing deficiency. The relations of such mutations with consanguineous marriage cannot be ruled out. Mutation screening is important in early onset breast cancer patients even if there is no family history. No significant financial relationships to disclose.
Survival analysis in breast cancer's women in Santa Catarina, south of Brazil
Authors: Schneider I. J. , Orsi E. D. , Furtado C. M. , Vianna A. , Silva T. S. 
Published: August 2020

e22149 Background: Overall survival after breast cancer diagnosis is influenced by the characteristics study's group, the study's place and biological factors. The prognostic factors are directly related to the survival of women with breast cancer. The studies indicate that the incidence and survival of breast cancer are influenced by socioeconomic factors and demographics. Methods: Define overall survival in five-years and the associated factors with the prognosis of breast cancer's women in Santa Catarina, Brazil. This is a historic cohort study, with data from diagnoses from January 2000 to December 2002 from Registro Hospitalar de Câncer of the Centro de Pesquisas Oncológicas, SC and the Hospital de Caridade, both in south Brazil, and complemented with data from the Mortality Information System until December 2007. The time of survival was calculated as the range of the date of diagnosis (biopsy or surgery) until the date of death or end of monitoring (5 years). The survival curves were estimated by the Kaplan-Meier method, using the log-rank test for comparison of the curves. The effect of co-variable model was estimated by the semi- parametric risk proportionate, Model Cox, with the Schoenfelder analysis of residuals to assess whether the co-variables of the final model respect the principle of proportionality over time. The analysis was made using R 2.5.0. Results: 1002 women were included, and 262 deaths occurred, this 235 by breast cancer. The overall survival after 5 years was 76,2% (73,6–78,9%). Variables were associated with survival by the Kaplan-Meier curves: age, race/color, education, clinical stage, treatments received. This includes these variables in the model of Cox, remaining in the final model, as independent factors: age until 30 years (HR: 3,09) illiterate (HR 3,70), staging III (HR 5,27) and staging IV (HR 14,07).The Cox model variables respect the principle of proportionality over time (p=0,25). Conclusions: The overall survival in breast cancer, proved to be better than in other Brazilian states. The instruction presents itself as a strong influence on survival, where illiterate women have worse prognosis. The diagnosis in advanced stages is one of the most important factors for worse survival, and modifiable through campaigns of early detection and mammography screening. No significant financial relationships to disclose.
Effect of panitumumab on autophagy in colon cancer
Authors: Kalofonos H. P. , Antonacopoulou A. , Matsouka P. , Giannopoulou E. 
Published: August 2020

e22151 Background: Panitumumab, a human monoclonal antibody raised against EGFR, has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of patients with EGFR-expressing mCRC and wild type kras. The ratio of reduced/oxidised form of glutathione (GSH/GSSG) is an indicator of the redox status in cells. The aim of the current study was to investigate the effect of panitumumab on the redox status of colon cancer cell lines Caco-2, DLD-1 and HT-29 regarding proliferation, apoptosis, necrosis, cell cycle arrest and autophagy. Methods: Cell proliferation was measured by MTT assay. Apoptosis and necrosis were detected by annexin v/propidium iodide assay. Cell cycle arrest was estimated by propidium iodide assay. Autophagy was detected by immunobloting and GSH levels were measured by spectrophotometrical analysis. kras mutations were detected by sequencing analysis. Results: Caco-2, DLD-1 and HT-29 cell lines differ in the expression levels of EGFR and HER-2. Kras mutation analysis in previous studies and in the current study showed that DLD-1 cells express mutated kras while Caco-2 and HT-29 cells express wild type of kras. Panitumumab decreased proliferation only in DLD-1 cells 48 h after its application besides the mutated kras. However, panitumumab did not affect DLD-1 cell apoptosis, necrosis or cell cycle progression 24 and 48 h after cells treatment. Interestingly, panitumumab increased protein levels of beclin 1, an indicator of autophagy, 24 h after its addition in cells. Moreover, an increase in GSH levels was noted 48 h after cells treatment with panitumumab. Conclusions: This is the first study to show that panitumumab, an EGFR inhibitor, affects colon cancer cell proliferation independently of kras mutations and EGFR protein levels through the induction of autophagy. The inhibition in cell proliferation was followed by an increase in GSH levels reflecting an imbalance on the redox status of cells. No significant financial relationships to disclose.