Detection and determination of tumor biomarkers are made from tissue and blood collection. During the last decade new biological sources are feasible: circulating tumor cells and circulating nucleic acids. They are composing a new field named as liquid biopsy. The availability of next-generation sequencing and Digital-PCR among other techniques, led to the possibility of getting the most out of this “circulating material” that would mirror the genetic and epigenetic features of the tumor.

Background: The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. Materials and Methods: Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank “Biobanco Público de Muestras Séricas Oncológicas” (BPMSO) of the “Instituto de Oncología “Ángel H. Roffo”. Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. Results: One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. Conclusion: Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival.

Malignant peripheral nerve sheath tumour (MPNST) is a rare and very aggressive tumour of nerve cell origin associated with poor prognosis. Incidence of MPNST is 1 per 1, 00,000 populations and it constitutes between 3%-10% of all soft tissue sarcomas1-4. MPNST have been found to be associated with neurofibromatosis type 1 (associated with mutation in NF-1 gene) in 2%-29% cases . Male and female are almost equally (53:47) involve. These tumours often create diagnostic dilemmas because of non-specific clinical diagnostic criteria, histopathological resemblance with other spindle cell sarcomas like monophasic synovial sarcoma, leiomyosarcoma and fibrosarcoma.

DNA methylation is a normal phenomenon which helps in gene expression, cell differentiation and is an inheritable process. Altered DNA methylation patterns in coding strands lead to epigenetic modification. These epigenetic changes enhances DNA adduct formation, somatic mutations and oncogene activation. During silencing of tumor suppressor genes, various genes/proteins involved in signaling pathways gets disturbed. These changes are reversible but if mutations occur they become irreversible. Hence early detection of these genes/proteins involved in epigenetic alterations may help in decreasing the associated changes in the body.

NPPB3-(4-5-nitro-2-(3-phenylpropylamino) benzoic acid, as one of the most commonly used chloride channel blockers, is very essential for chloride channel studies. However, the role of NPPB in mediating apoptosis is uncertain. The purpose of this study was to investigate the apoptosis mechanism of NPPB in human cancer DU145 cell lines. Cell viability was examined by MTT assay. JC-1 fluorescent probe was used for detecting l membrane potential. Cell apoptosis was determined by flow method (FCM). The expression of apoptosis-related protein Caspase-3, Cleaved caspase-3, PARP, Cleaved PARP, Bcl-2, Mcl-1, Bcl-xl, Bcl-w and Bax was detected by western blotting. Cell proliferation rate was remarkably inhibited 2 h after treating with NPPB(50,100 μmol/L) (p<0.01); Flow cytometry method analysis showed that the apoptosis rate in each treated group were significantly higher, especially for the promotion of early apoptosis rate effect was significantly (P<0.05); Images of JC-1 showed NPPB led to the decrease of intracellular mitochondrial membrane potential; Western blot results showed that caspase-3/PARP signaling pathway was activated, while the expression of cleaved caspase-3, cleaved PARP was significantly increased (P<0.01).PARP, as substrate of caspase-3, was significantly decreased (P<0.05).Bcl-2, Bcl-xl compared with the control group had no significant difference, and anti-apoptotic protein Mcl-1 (P<0.05) and Bcl-w (P<0.01) decreased significantly, pro-apoptotic protein Bax (P<0.01) were obviously upregulated. Our findings indicated that NPPB could increase apoptosis in DU145 cell lines via mitochondria-related apoptotic pathway, and following results presented that ClC-3 Chloride Channels involved in the process of NPPB induced DU145 cells apoptosis.

Background: tRNA and ARS, tRN-A-RS, pivot the translational machinery. How their aberrances correlate to diseases, neurological conditions, metabolic disorders, and cancer is the purpose of this study.

Methods: Information was retrieved from the literature and from databases, such as OMIM and MITOMAP, related to disease and cancer. Changes of expressions of ARSs were assessed from analyzing NGS data available from TCGA, ENCODE and lately from roadmap epigenomics.

Results: A total of 647 tRNAs and 37 ARSs reside in the genomic pool of human, aberrant expressions of some of the nuclear tRNAs and cytoplasmic ARSs correlate predominately to cancer, while anomalous pathways in mitochondria relate more to other diseases. tRNA fragments juggle between tumor suppressor and oncogenic pathways. Brain cancer and neurological disorders seem to gain impetus from translation machinery components. However, investigation of the causes of the diseases particularly cancer due to the aberrations continues to be hamstrung by the lack of deep sequencing reads of tRNAs in different cell lines, and this needs to be addressed.

Conclusions: Increased cell proliferation requires elevated protein synthesis levels and makes the correlation between tumour cells and deregulated tRN-A-RS components in translation plausible. We draw the network of tRN-A-RS with cancer and other diseases, and present and expand on some of the hypotheses on the underlying molecular mechanisms, opening up new avenues for research.

Neurologically, BRAF V600E mutation was detected in cerebellar anaplastic pilocytic astrocytoma, ganglioglioma, desmoplastic infantile astrocytoma, indeterminate cell tumor and interdigitating dendritic cell sarcoma. Hematologically, BRAF V600E mutation was also detected in multiple myeloma and several leukemias (hairy cell, chronic lymphocytic, prolymphocytic and acute lymphoblastic leukaemia).

Bo Franzén, Roland Sennerstam, Hans Wiksell, and Gert Auer

Purpose: Glioblastoma (GB) patients usually have symptoms that affect their functional status, and medical staff, as well as the patients and their caregivers, might have different perceptions about it. The performance status is important to establish a patient’s survival prediction and treatment decisions. This study was aimed to explore whether health care providers, patients, and caregivers have a common perception of patients’ functional statuses and to investigate in further studies whether the functional scales used in oncology clinical practice are objective tools to evaluate brain tumour patients.

Methods: GB patients treated at our Neuro-Oncology Unit were evaluated once using Eastern Cooperative Oncology Group Performance Status (ECOG) and Karnofsky Performance Status (KPS) by a medical oncologist (MO), an independent investigator (II), the patient and the patient’s main caregiver.

Results: Fifty patients were enrolled. Concordance in KPS evaluation among the four observers was low (Fleiss’ Kappa=0.354; p<0.001) and moderate in ECOG one (Fleiss’ K=0.424; p<0.001). Pairing the observers, the concordance between the MO and II was strong (KPS Cohen’s Kappa=0.731; p<0.001, ECOG Cohen’s Kappa=0.741; p=0.001), whereas it was poor between the patient and MO (KPS Cohen’s Kappa=0.250; p=0.007. ECOG Cohen’s Kappa=0.241; p=0.009) and between the caregiver and MO (KPS Cohen’s Kappa=0.350; p<0.001. ECOG Cohen’s Kappa=0.346; p=0.000).

Conclusion: Concordance among the observers was poor or moderate according to the functional scale used. Particularly, caregivers’ perception of the patients’ functional status was frequently worse than that of the professionals.

Lung cancer is the leading cause of cancer related deaths in general population. Early diagnosis of malignant pulmonary nodule, can improve 5-year survival rate of lung cancer by upto 80%. There is increase in incidentally detected pulmonary nodules with the increased usage of diagnostic imaging modalities especially computed tomography (CT) of chest. Most often, physicians and trainee doctors have to depend on the experienced radiologists to confidently label these nodules as benign or malignant, thereby raising a need for some method, which could help them in self-learning and also could assist radiologists in ruling out malignancy with good certainty and confidence.

Aim: Colonoscopy screening of colorectal neoplasm in first-degree relatives is reported frequently, and is recommended in guidelines. However, data from China is limited. This observation study is to evaluate the current situation in Dongguan, China.

Methods: All first-degree relatives were recommended to perform colonoscopy screening when a proband is found in a family. They were divided into 3 groups, the down, up and crossing screening group (children, parents and siblings of proband). Control group rolled in healthy people who underwent colonoscopy while medical examination in our hospital. All subjects ranged from 30-80 (not included) years old. Advanced colorectal neoplasm is defined as: high-grade adenoma, villioustublar adenoma, adenoma with diameter ≧ 1 cm and colorectal cancer. Colonoscopy findings of lesions, site and size of the ACNs and polyp, pathology results of all subjects were recorded. Statistical analysis was run with SPSS 19.0.

Results: In 52 subjects of the Down screening group, 6 were found to be CANs, 9 were adenoma, the overall morbidity in the group is 28.8%. 8 out of 43 subjects in up screening group were found CANs, 7 were adenoma, making the overall morbidity is 34.9% of the group. There were 3 subjects in crossing screening group out of 28 found to be CANs, 5 subjects were adenoma, overall morbidity of the group is 28.6%. Comparing to the control group, there were 176 subjects involved, 15 of them were found to be CANs, 9 were found adenoma, overall morbidity is 13.6% in control group. Statistical analysis indicates that there were significant statistical differences when comparing the down, up and crossing screening group to control group (all p<0.05).

Conclusion: First-degree relatives of proband in Dongguan have a high incidence of colorectal neoplasm, it is recommended to run colonoscopy screening. And it is better understanding as ‘Cruciform screening’ while screening of first-degree relatives.

Background: To compare the real-world performance of visual inspection with acetic acid and with Lugol’s iodine (VIA/VILI), cytology and careHPV DNA assay in rural China performed by local health providers.

Methods: Eligible women living in rural areas in Xinmi County, Henan Province were invited to participate in cervical cancer screening program. Enrolled women were randomized into 3 intervention arms, screened by VIA/ VILI, pap smears, and careHPV assay respectively. Women had positive primary screening results were referred to colposcopy and/or biopsy. All the clinical and lab work was performed by local health providers. The final diagnoses of histopathology were based on the diagnosing of a senior histopathology expert from Cancer Hospital, Chinese Academy of Medical Sciences. Questionnaires about the knowledge and attitudes towards the HPV and the screening program of the health providers at village clinics were collected.

Results: 894 women had careHPV DNA test, 552 underwent VIA/VILI and 547 had Pap smears. The positive rates for careHPV assay, VIA/VILI and Pap smears were 10.6%, 18.1%, and 4.9% respectively (χ2=48.647, P<0.001). The overall CIN2+ detection rate was 0.5%, the CIN2+ detection rate for the three arms were not significantly different (0.7% for careHPV assay, 0.5% for VIA/VILI, 0.2% for pap smear, χ2=1.648, P=0.439). The knowledge of the health providers about HPV, HPV assay in screening was unsatisfactory. However, their attitudes about implementing HPV assay into the national program were positive.

Conclusion: Implementing careHPV assay in low resource settings and performed by simply trained lab personnel is feasible. For large population screening program, extensive training and good quality control are needed to improve the quality. Education for implementing HPV assay in local health providers are needed.

Background: Notch pathway is involved in regulating colon cancer stem cells (CSCs), which play an important role in angiogenesis and resistance to conventional therapies. CD44 and CD133 are transmembrane glycoproteins reported as putative markers for isolating CSCs. High expression of Notch Intracellular Cleaved Domain (NICD) has been associated with resistance to anti-vascular endothelial growth factor therapy. Based on these reports, we evaluated NICD, CD44 and CD133 expression in a series of consecutive metastatic colon cancer patients treated with bevacizumab-based chemotherapy within first-line clinical trials.

Methods: Histological samples obtained from 45 primary adenocarcinomas were tested by immunohistochemistry for NICD, CD44 and CD133. A scoring system based on staining intensity and percentage of stained cells was used. Vessels density was measured in hot-spot areas by CD31 antibody.

Results: CD44 levels were higher in high NICD cases than in low NICD cases (63% vs. 16%, respectively, p=0.014). High NICD and CD44 levels predicted shorter progression-free (p<0.001) and overall survival (p=0.012). No significant association was found between CD133 or CD31 and NICD or CD44 expression.

Conclusion: Our data suggest that colon cancer patient with high NICD and CD44 levels have a reduced likelihood of response to bevacizumab-based therapy.

Breast cancer is the most frequent malignancy with high mortality among woman around the world. Global DNA methylation has been investigated by multiple studies and suggested as a screening biomarker for cancer. DNA methylation for two repetitive elements, LINE1 and Alu, was investigated in whole blood DNA from 229 breast cancer patients and 151 controls by using MassARRAY EpiTyper assay. Results showed that the mean methylation level of investigated CpG sites of LINE1 in peripheral blood from breast cancer patients was lower than that in controls (P=8.78E-06), especially for one specific CpG site (LINE1_CpG_1 with P=3.64E-10). ROC curve analysis of LINE1_CpG_1 methylation and LINE1 mean methylation was used to estimate the potential clinical utility of LINE1 methylation, area under the curve (AUC) was 0.73 (95% confidence interval (CI): 0.68-0.79) and 0.68 (95% CI: 0.62-0.74), respectively. In addition, the highest increased risk was observed in the lowest quartile of LINE1_CpG_1 methylation and LINE1 mean methylation (odds ratio (OR)=38.47 and 5.94; 95% CI: 8.77-168.64 and 2.94-11.98; P for trend=1.42E-07 and 1.33E-05 respectively). For Alu, significant hypomethylation of Alu_CpG_13 and Alu_ CpG_14 in peripheral blood of breast cancer cases compared to controls was observed (P=0.002 and P=0.006). For the combined analysis, the AUC of the 10 most important CpG sites of LINE1 and Alu is 0.77 (95% CI: 0.72-0.83). Our study indicates that hypomethylation of specific CpG sites in LINE1 and Alu elements in peripheral blood DNA could be potential biomarkers for breast cancer risk. Further multicenter prospective studies are needed to verify these results.

Circulating Tumor Cells (CTCs) are considered a liquid biopsy of solid tumors, reflecting the disease complexity at any stage of cancer progression. CTCs, in fact, represent a surrogate material of the tumor which can be obtained by a minimally invasive blood draw and used for disease monitoring and orienting therapeutic decisions, but their detection and characterization are technically challenging.