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// Marcus Vetter 1,* , Spyridon Fokas 2,* , Ewelina Biskup 3,7 , Thomas Schmid 4 , Fabienne Schwab 2 , Andreas Schoetzau 2 , Uwe Guth 5 , Christoph Rochlitz 1 and Rosanna Zanetti-Dallenbach 6 1 Department of Medical Oncology, University Hospital Basel, Basel, Switzerland 2 Women’s Hospital,University Hospital Basel, Basel, Switzerland 3 Department of Internal Medicine, University Hospital Basel, Basel, Switzerland 4 The Royal Marsden Hospital, London, United Kingdom 5 Brust-Zentrum Zurich, Zurich, Switzerland 6 Sankt Claraspital, Basel, Switzerland 7 Shanghai University of Medicine and Health Sciences, Department of Basic Medical College, Shanghai, PR China * These authors have contributed equally to this work Correspondence to: Marcus Vetter, email: // Keywords : early breast cancer, triple negative breast cancer, chemotherapy, carboplatin, platinum-based chemotherapy Received : November 30, 2016 Accepted : April 10, 2017 Published : May 23, 2017 Abstract Background: Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. Methods: We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients. All patients with stage I-III TNBC who underwent primary breast surgery between 2004 and 2014 were included. Results: Eighty-three patients were included in the analysis. Stage and grade were well balanced between patients treated with standard chemotherapy ( N =54; cohort A) or standard chemotherapy plus carboplatin ( N =29; cohort B). The median time to local relapse (LRFS) was 15.0 months in cohort A versus 16.0 months in cohort B ( p =0.655). The median time to distant relapse (DRFS) was 29.5 months in cohort A versus 25.0 months in cohort B ( p =0.606) There was also no difference in overall survival between the two cohorts (mean overall survival 98 and 91 months, respectively; p =0.208). Discussion: Our data suggest that in an unselected cohort of early TNBC patients, the addition of carboplatin in the adjuvant setting may not be beneficial with respect to relapse-free and overall survival. Further prospective trials to evaluate the addition of platinum in the adjuvant setting are warranted, especially to define subgroups of TNBC patients, which might benefit from carboplatin therapy.

// Lan Zhong 1, * , Jing Liu 2, * , Yedong Hu 1 , Wei Wang 1 , Fei Xu 1 , Wen Xu 1 , Junyi Han 3 , Ewelina Biskup 4 1 Department of Gastroenterology, East Hospital of Tongji University School of Medicine, Shanghai, China 2 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China 3 Department of General Surgery, East Hospital of Tongji University School of Medicine, Shanghai, China 4 Department of Internal Medicine, University Hospital of Basel, Switzerland * These authors contributed equally to this work Correspondence to: Junyi Han, email: doctortonyhjy@163.com Keywords: colorectal cancer, metastasis, serine–threonine kinase 31 (STK31), cancer testis antigen Received: August 25, 2016 Accepted: February 01, 2017 Published: February 16, 2017 ABSTRACT Purpose: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in China and fourth worldwide. Metastatic dissemination of primary tumors is considered main cause for CRC related mortality. The serine–threonine kinase 31 (STK31) gene is a novel cancer testis (CT) antigen. It was found significantly highly expressed in gastrointestinal cancers. In our study we aimed to analyze the correlation between STK31 expression patterns and metastasization, tumor stage and grade in CRC patients. Results: Relative STK31 expression level was significantly higher in patients with lymph node metastasis. STK31 expression levels in primary tumorous tissues of metastatic patients were significantly higher than in ANCTs and in lymph nodes samples, both at the RNA level and the protein level. Materials and Methods: Surgical specimens of cancerous tissues, paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with different clinicopathological features were collected. Expression of STK31 was detected and measured by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). Conclusions: Our data suggest that STK31 might be a potential biomarker in detecting, monitoring and predicting the metastatic risk of colorectal cancer.

// Feng-Feng Cai 1, * , Cheng Xu 1, * , Xin Pan 2 , Lu Cai 1 , Xiao-Yan Lin 1 , Su Chen 3 , Ewelina Biskup 4 1 Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China 2 Department of Central Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China 3 Department of Molecular and Cellular Biology, School of Forensic Sciences, Xi’an Jiao Tong University Health Science Center, Xi’an, Shaanxi, PR China 4 Department of Oncology, Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland * These authors have contributed equally to this work Correspondence to: Feng-Feng Cai, email: caifengfeng@medmail.com.cn Su Chen, email: chensu@mail.xjtu.edu.cn Ewelina Biskup, email: ewelinabiskup@yahoo.de Keywords: breast cancer, HIF-1α, PGC-1α, prognosis, ELISA Received: July 22, 2016 Accepted: October 10, 2016 Published: October 21, 2016 ABSTRACT Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator–activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.

BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis.

// Xian-Peng Li 1,* , Xiao-Yu Yang 2,* , Ewelina Biskup 3 , Jiang Zhou 1 , Hong-Liang Li 1 , Yi-Feng Wu 4 , Ming-Liang Chen 4 and Feng Xu 1 1 Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China 2 Division of Special Treatment II, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 Department of Oncology, University Hospital of Basel, Basel, Switzerland 4 Division of Hepatobiliary Surgery, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, China * These authors contributed equally to this study and should be considered as co-first authors Correspondence to: Feng Xu, email: // Keywords : IL-8, cytokines, migration, hypoxia, metastasis, HCC Received : February 04, 2015 Accepted : May 25, 2015 Published : June 10, 2015 Abstract Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.