bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation risks to lymphoma patients undergoing 18F-FDG studies
Authors: Hardin L. V. , Ravenel J. , Gordon L. , Huda W. , Mah E. 
Published: August 2020

e22024 Background: To investigate radiation risks to patients undergoing 18F-FDG studies that take into account patient age, sex, and weight. Methods: We obtained patient demographics and weights of 54 consecutive patients with lymphoma who each underwent a18F-FDG PET study. The administered activity was converted into an effective dose using the patient size dependent dosimetry data provided in ICRP Publication 80. Patient effective doses were converted into estimates of the lifetime attributable risk of cancer incidence and cancer mortality using age and sex dependent risk factors provided in BEIR VII. Results: The average patient age/weight in this study was 43 years/68 kg for males and 33 years/61 kg for females. Patient effective dose are proportional to patient weight(-0.784) (r2 >0.99). The average administered activity was 410 MBq, which resulted in an average effective dose of 8.5 mSv for males and 8.9 mSv for females. The average cancer incidence was 0.71/1,000 cases for males, and 1.27/1,000 cases for females, with cancer mortality being about half the incidence. Cancer rates for the youngest patients were an order of magnitude higher than those for the oldest patients. Conclusions: Average lifetime attributable cancer risks to lymphoma patients from a single FDG-PET study is approximately 1 per 1,000, but are strongly influenced by patient age, gender and weight. Cancer risk in younger patients is a magnitude of order greater. No significant financial relationships to disclose.
Interaction between the p53 genotype of lung cancer and response to mTOR inhibitor combined with irradiation therapy
Authors: Nagata Y. , Tojo T. , Ohnishi K. , Takahashi A. , Ohnishi T. , Taniguchi S. 
Published: August 2020

e22028 Background: Frequent activation of the PI3K/Akt/mTOR pathway and aberrations of tumor suppressor gene p53 are associated with therapeutic resistance in lung cancer. Nevertheless, the possibility of the variants of p53 genotype to affect response to mTOR inhibitor combined with irradiation therapy remains still unclear. Methods: Human non-small lung cancer cell line H1299 with p53 null genotype, was transfected with wild type or mutated p53 gene (H1299/wtp53 (WT), H1299/mp53 (MT)). Both cell survival and cell proliferation were estimated by colony formation assay to assess differences between WT and MT in sensitivity to rapamycin and ability of rapamycin to enhance radiation sensitivity. Cells were treated according to the individual study; DMSO (control), rapamycin (100 nM for 1 hour), irradiation (IR) (increasing doses), combination (RR) (rapamycin followed by irradiation). Changes in the cell cycle were also analyzed by flow cytometry. Results: Rapamycin decreased cell survival only in WT (P < 0.01, vs. control). MT was resistant to rapamycin exhibiting slightly inhibited cell proliferation. Compared with IR, RR with no less than 6 Gy radiation enhanced inhibitory effects on both cell survival and proliferation independent of p53 genotype (P < 0.01 in WT and P < 0.01 in MT, respectively), that indicating additive interaction. Cell cycle analysis demonstrated rapamycin induced G1 cell cycle arrest in both types of cells compared with controls (P < 0.01 in WT and P < 0.05 in MT, respectively) at 24 hours after treatment. Enhancement of G1 arrest by RR was observed in both WT (P < 0.01, vs. IR) and MT (P < 0.01, vs. IR) at the same time point. In addition, RR caused a greater reduction of cells in S phase than that of IR regardless of p53 gene status (P < 0.01 in WT and P < 0.01 in MT, respectively). Conclusions: Rapamycin is an effective radiosensitizer in a p53 independent manner, in which increased G1 cell cycle arrest and decrease in S phase cells are responsible for increased growth inhibitory effect. It will enable us to provide more appropriate treatment to patients with mutated p53 gene. No significant financial relationships to disclose.
Use of gene expression profiling to identify fibronectin 1 and MIG as candidate biomarkers for breast cancer screening
Authors: Ruiz-Garcia E. B. , Scott V. , Machavoine C. , Bidart J. M. , Lacroix L. , Delaloge S. , Andre F. 
Published: August 2020

e22034 Background: There is a need to develop blood-based bioassays for breast cancer screening. We used differential gene expression between breast cancer samples and benign tumors to identify candidate biomarkers for blood-based screening Methods: 3 candidate proteins (Fibronectin 1, CXCL9, Complement Factor B) were identified from a gene expression dataset that included 120 breast cancer samples and 45 benign lesions. Proteins selection was done with these criteria: differential gene expression between cancer and benign lesion, protein released in the extracellular medium (SwissProt), commercially available ELISAkit, accuracy of the ELISA assay in a feasibility study (n=23). Proteins concentrations were determined in blood samples by ELISA. Blood samples were from normal volunteers blood donors (n=119) and early breast cancer patients (n=133). Results: 73% of the patients were cT1-T2 tumour. CA15.3 was within normal range (<30 IU/ml) in 114 patients (86%). Blood concentrations of CXCL9 and Fibronectin 1 were higher in cancer patients as compared to normal volunteers, mean concentration for CXCL9 was 851pg/ml (range 121- 3941) and 635 pg/ml (range 12–4327) in cancer patients and normal volunteers respectively (p=0.013). CXCL9 concentration was significantly higher in patients with ER-negative breast cancer (mean: 999 pg/ml) as compared to normal volunteers (p=0.003), data consistent with gene expression profile. Fibronectin 1 mean concentration was 190 μg/ml (range 11–326) for cancer patients and 125 μg/ml (range 58–212) for normal volunteers (p<0.001). AUC for breast cancer diagnosis were 0.78 and 0.62 for Fibronectin 1 and CXCL9 respectively. A combined score including Fibronectin 1 and CXCL9 dosages presented a sensitivity of 53% and a 98% specificity. Similar performances were observed for ER-negative tumors Conclusions: This study suggests that Fibronectin 1/CXCL9 dosage in serum could screen a significant rate of breast cancer, including ER-negative breast cancer. These data suggest that analysis of differential gene expression is a good approach to select candidate biomarker to set-up blood assays cancer screening. Prospective validation of the combined score, and development of in house ELISA assay for 25 additional proteins are ongoing. No significant financial relationships to disclose.
The role of whole body 18F-FDG PET/CT scan in patients with carcinoma of unknown primary
Authors: Hu M. , Yu J. , Liu N. , Kong L. , Zhang P. 
Published: August 2020

e22051 Background: Carcinoma of unknown primary (CUP) is a heterogeneous group of tumors and usually follows an aggressive biological and clinical behavior. Difficult challenges in oncology which the identification of the primary tumor and a complete disease staging could offer a more rational and efficient treatment in order to improve the survival time. Our aim was to evaluate the role of 18F-FDG PET/CT scan with two aspects: detection of the primary site, and estimation of tumor biological behavior which essential for the development of new, individual and targeted effective therapies. Methods: One hundred and seventeen patients presenting with histologically confirmed metastatic carcinoma (76 lymph nodes, 41 visceral biopsy proven) of unknown primary site were included in this retrospective study. The evaluations as follows had not revealed a primary site: detailed medical history, full physical and laboratory examinations, and diagnostic imaging methods. All patients underwent PET/CT. Results: In 42 (35.90%) patients, a primary tumor site which was confirmed by follow-up or surgery was showed by PET/CT. In 15 (12.82%) patients, the primary tumor site was suggested by PET/CT but not confirmed. In 60 (51.28%) patients, the primary tumor site was not localized modifying the stage of disease. In the other 17 (14.53%) patients, PET/CT scan identified further unexpected metastases. Overall, the following oncological treatment was influenced by the PET/CT scan, in a total of 38 (32.47%) patients. Between the adenocarcinoma and squamous cell carcinoma groups, no significant difference in SUVmax was found ( t=1.191, p = 0.244). A significantly higher SUVmax was found among patients with poorly or undifferentiated carcinoma compared with patients with well to moderately ( t=4.013, p<0.01) differentiation; In 42 patients with a confirmed primary tumor site, the SUVmax of Metastatic tumours have a closely relationship correlate with those of primary tumours, ( r=0.738, p<0.01). Furthermore, a significantly higher SUVmax was found among metastases compared with primary tumors ( t=3.470, p<0.01). Conclusions: Our data strongly support 18F-FDG PET/ CT imagings not only provide new insights in the diagnosis and staging of patients with CUP, but also evaluate biologic characters of tissue. 1 No significant financial relationships to disclose.
Protective effect of metformin in lung cancer patients
Authors: Gagnon B. , Roseman M. , Kasymjanova G. , MacDonald N. , Kreisman H. , Small D. 
Published: August 2020

e22063 Background: Over the past decade, dozens of studies have shown that metformin not only decreases mortality in diabetics, it also significantly reduces CRP and reduces the risks of cancer in rodent and human cell lines. We report on the survival of lung cancer patients concomitantly exposed to metformin in our community-based program. Methods: 850 patients undergoing treatment from a prospectively collected pulmonary oncology database of the SMBD-Jewish General Hospital over an 8-year period were analyzed. Pilot observational study of survival was performed using Cox regression model. The factors that were included in the model were age, gender, stage, histology and metformin use. Results: 850 patients (F: M=375:475; mean age of 66) were diagnosed since 2000 and followed in pulmonary oncology outpatient clinic for NSCLC. 523 (62%) of those patients were diagnosed with adenocarcinoma; 488 (57%) were stage IIIB with pleural effusion/IV. 79(9%) patients were receiving treatment with metformin for their comorbid type 2 diabetes. The Cox regression analysis demonstrated that age, gender, stage and use of metformin were significant prognostic factors for survival. The use of metformin is associated with a 37% (HR 1.37; CI 1.01–1.84) (p=0.039) increase in survival. Conclusions: Thus, the result obtained from our model suggests that use of metformin may be associated with better survival of lung cancer patients. As this is a pilot study, we will consider alternative explanations. No significant financial relationships to disclose.
Interactions of breast cancer cells with the microenvironment of the human bone marrow
Authors: Kaiser T. , Klein G. , Solomayer E. , Wallwiener D. , Fehm T. 
Published: August 2020

e22097 Background: Bone is one of the most favored sites for metastasis of breast cancer cells (BrCa) resulting in the formation of osteolytic and/or osteoblastic lesions. There is increasing evidence that the bone marrow (BM) microenvironment plays a pivotal role in modulating tumor cell homing to the bone, metastasis and progression. However, the molecular crosstalk between BrCa cells and the cellular and extracellular components of the bone marrow leading to osteotropism still remains a poorly characterized step in the metastatic process. Methods: Cell adhesion and migration assays using the invasive MDA-MB-231 and the noninvasive MCF7 BrCa cell lines were performed to investigate the impact of BM components on cellular functions of tumor cells. Results: Cell-matrix adhesion assays showed a strong and concentration-dependent attachment of BrCa cells to several extracellular matrix components present in the human bone marrow such as fibronectin, different laminin isoforms, collagens type I and IV or tenascin-C. Moreover, the BrCa cells attached avidly to the BM-derived primary osteoblasts, whereas the binding to stromal cells was significantly weaker. Notably, cell-cell adhesion experiments with primary osteoclasts revealed an anti-adhesive effect on tumor cell binding leading to no attachment activity of BrCa cells with the cell surface of primary osteoclasts. The influence of cellular components of the BM on tumor cell migration was analyzed by cell migration assays using conditioned media of osteoblasts, osteoclasts and stromal cells or a modified Transwell chamber technique. The migration assays with invasive MDA-MB-231 cells clearly showed that osteoblasts, but not osteoclasts or stromal cells released factors which led to a faster wound closure, suggesting an enhanced migratory ability of the metastatic tumor cells, whereas the migration of nonmetastatic MCF7 cells was unaffected. Conclusions: These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease. No significant financial relationships to disclose.
Preliminary validation of two novel immunoassays for detecting VEGF in human and mouse plasma using single molecule counting technology
Authors: Puskas R. , Held D. , Sheets D. , Klein B. K. , Macy E. , Agee S. J. , Todd J. 
Published: August 2020

e22099 Background: Growth in biomarkers as therapeutic targets and as surrogate markers for efficacy presents a need for increasingly sensitive immunoassays to expand biomarker applicability. Improved immunoassays will provide: (1) better evaluation and validation of new drug candidates, (2) better matching of patients to new therapies, (3) accelerated drug approval (4) earlier diagnosis of at-risk patients, and (5) a deeper understanding of cancer biology. Towards this end, Singulex has developed two ultra- sensitive VEGF Immunoassays for human and mouse vascular endothelial growth factor (VEGF). Here we report the preliminary validation of these two novel assays. Methods: Two novel assays were developed with the Erenna Immunoassay System for detecting VEGF: human (hVEGF) and mouse (mVEGF). Analytical sensitivity, cross-reactivity and precision were determined and compared to an ELISA based VEGF assay. Both the Singulex assay and ELISA assay were used to test a range of specimen types (plasma, cell lysates, conditioned media, and tissue specimens) from humans and mice. Preliminary assays with human plasma and tissue specimens were conducted to compare hVEGF levels between normal and breast cancer samples. Results: The Singulex hVEGF assay had an LOD of 0.1 pg/mL, an LLOQ of 0.3 pg/mL, and 84–107% spike recovery; 90X more sensitive than the ELISA assay. Human VEGF concentrations were quantified in all specimens tested compared to the ELISA, which quantified VEGF in only 8% of plasma samples, but all of the cell lysate samples. The Singulex mVEGF assay had an LOD of 3.5 pg/mL, LLOQ of 5 pg/mL, and 68–111% spike recovery; 3X more sensitive than the ELISA assay. Cross-reactivity for the two assays was minimal for all specimen types tested, except for human plasma samples where the mVEGF assay demonstrated 80–100% CR. Conclusions: We show that the Singulex hVEGF and mVEGF Immunoassays can detect VEGF at or below pg/mL levels, and can effectively quantify VEGF levels in plasma, cell lysates, conditioned media, and tissue samples from mice and humans. These novel assays are an important tool when used to assess tumor and normal breast cancer tissue and plasma. [Table: see text]
Prognostic significance of BRCA1, PARP1, and PARP2 in sporadic breast cancer
Authors: Gennari A. , Sormani M. , Varesco L. , Pronzato P. , Viassolo V. , Mirisola V. , Pfeffer U. , Bruzzi P. 
Published: August 2020

e22114 Background: Breast cancer susceptibility gene (BRCA1) is a tumor suppressor gene whose mutation is associated with the development of hereditary breast cancer. In sporadic tumors, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, has been suggested to be associated with prognosis. Cells with BRCA1 loss of function are deficient in DNA double strand break repair thus activating poly(ADP-ribose) polymerases (PARPs) whose catalytic activity is immediately stimulated by DNA strand-breaks. The aim of this study was to evaluate the prognostic value of BRCA1 and PARPs (PARP1 and 2) in sporadic breast cancer. Methods: We merged two previously published Affymetrix gene expression datasets: GSE 1456 (159 patients, median follow up 7 years) and GSE 2494 (249 patients, median follow up 10 years). Microarray data preprocessing was carried out using Bioconductor software (gcrma procedure). Expression of BRCA1, PARP1 and PARP2 mRNA were evaluated as continuous variables. Kaplan Meier survival curves and Cox regression analysis (stratified by database) were used to assess the prognostic capability of the identified biomarkers. Results: High mRNA expression of BRCA1, PARP1 and PARP2 was correlated with an adverse prognosis. Relapse Free Survival (RFS) Hazard Ratio was 1.6 (95% CI, 1.2 to 2.1) for BRCA1 (p = 0.002), 1.7 (95% CI, 1.2 to 2.4) for PARP1 (p = 0.002) and 1.7 (95% CI, 1.3 to 2.3) for PARP2 (p = 0.001). By multivariate analysis all 3 genes resulted independently correlated with RFS. When interaction with systemic adjuvant therapy (107 patients treated) was tested, BRCA1 mRNA expression was strongly associated with treatment: HR 2.3 (95% CI, 1.4 to 3.7, p 0.001); p for interaction = 0.06. Conclusions: This study shows that BRCA1, PARP1 and PARP2 are all significantly associated with prognosis in sporadic breast cancer. No significant financial relationships to disclose.
Clinicopathologic and prognostic features of triple-negative breast cancer analyzed in registration data of the Japanese Breast Cancer Society, 11705 cases
Authors: Iwase H. , Yamamoto Y. , Kurebayashi J. , Tsuda H. , Ota T. , Kurosumi M. , Miyamoto K. , Iwase T. 
Published: August 2020

e22122 Background: Triple-negative (TN) breast cancers which are negative for ER, PgR, and HER2 by immunohistochemistry are associated with a poor prognosis. To clarify the characteristics of TN tumors, the data of the registration committee of the Japanese Breast Cancer Society were analyzed with respect to clinicopathologic factors, response to neoadjuvant chemotherapy (NAC) and prognosis. Methods: Of 14,748 cases that were registered in 2004, 11,705 cases (79.4%) were examined for ER, PgR, and HER2 status, which was based on local institute. In the 2,331 cases of all registered cases, the prognosis and details of the treatment were analyzed with 47.8 months as median follow-up period. In 184 cases (7.9%), NAC was mainly performed using anthracycline and taxane based chemotherapy. Results: Luminal A type with positive for ER and/or PgR and negative for HER2 was most prevalent (53.8%), followed by TN type (15.5%). TN cancers were diagnosed at a slightly advanced stage and more of the cases had lymph node metastases compared to other types. Mucinous or tubular carcinoma was frequently seen in the Luminal A type. Squamous cell, spindle cell carcinoma, or metaplastic carcinoma with bone/cartilage metaplasia was found in only TN type. The HER2 type and TN type had statistically worse outcome compared to Luminal type in DFS and OS (P<.0001 and P<.0001, respectively). Pathological response rate of NAC, including grade 2 and 3, was higher in TN tumor as 51.5 % (22/53) than in Luminal A tumor as 16.7% (12/72). Responders in TN tumors have a better prognosis than non-responder (P=.0016), but this tendency was not recognized in non-TN tumors (P=.15). Conclusions: The ratio of the TN tumors in Japan was 15–6%. Central reviews of immunohistochemistry, such as ER, PgR, HER2, CK5/6, EGFR etc, will be confirmed in this cohort, for TN tumors are similar to basal-like tumors discriminated by gene- profiling. [Table: see text]
Preliminary report of the mutation status of KRAS and BRAF-V600E in an Argentinean population of primary colorectal tumors
Authors: Perazzo F. , Denninghoff V. , Pasccon G. , Pallotta M. G. , Tatangelo M. , Cuartero V. , Kirchuck R. , Chacón M. , Gennari L. , Vera K. , Avagnina A. 
Published: August 2020

e22183 Background: Several studies have suggested that KRAS somatic mutations predict resistance to Cetuximab treatment in colorectal cancers. The aim of this report is to present the mutational status of KRAS, BRAF and epidemiological data of an Argentinean population of CR tumors which may have future clinical practice implications. Methods: Patients were prospectively selected from the databases of 8 Argentinean public and private hospitals with colorectal cancer between January and December 2008. We analyzed the presence of KRAS point mutations in codons 12 and 13, and the BRAF-V600E from formalin fixed sections with Polymerase Chain Reaction (PCR) amplification-sequencing. Results: A total of 146 patients, 41.8% (61) F and 57.2% (85) M, with a median age of 58.1 years (range, 17–88), 45.2% (66) were current smokers, 50% (73) never smoke. 41.4% (60) have family history of cancer and 9.6% (14) have personal history of a previous tumor. 63.2% were European Caucasian, 30.3% American Caucasian and 0.7% of Asian origin. The media BMI was 25.9 (range, 16- 47). The primary tumor site was 21.9% (32) right colon, 5.5% (8) transverse colon, 45.2% (66) left colon and 27.4%(40) rectal cancer. Adenocarcinoma was the unique histotype and mucinous differentiation was observed in 14.7% (21). The Pathological Stage at diagnosis was Stage I 3.42% (5), II 24% (35), III 33.6% (49) and IV 39% (57). 60.3% (88) where found to be wild type, while the other 39.7% (58) showed the KRAS mutation in the following amino acids: GLY12ALA 5.2% (3), GLY12ASP 25.9% (15), GLY12CYS 3.4% (2), GLY12SER 1.7% (1), GLY12VAL 62.1 % (36), GLY13ARG 1.7% (1). We analyzed in 49 patients the mutational status of BRAF-V600E, only 2 patients showed the presence of both mutations, 23 presented BRAF and KRAS wild type, 20 had a KRAS mutation while the BRAF was wild type, only 4 patients reveled a mutation of BRAF in the presence of a KRAS wild type. Conclusions: This is the first Argentinean collaborative study of the mutational status of KRAS and BRAF. Our preliminary report based in 146 patients, revealed similar mutational KRAS results in codon 12 and 13 than the reports of Europe. This is probably due to the ethnic origin of Argentinean population. No significant financial relationships to disclose.