Molecular Oncology

SALL2 is a poorly characterized transcription factor that belongs to the Spalt-like family involved in development. Mutations on SALL2 have been associated with ocular coloboma and cancer. In cancers, SALL2 is deregulated, and is proposed as a tumor suppressor in ovarian cancer. SALL2 has been implicated in stemness, cell death, proliferation and quiescence. However, mechanisms underlying roles of SALL2 related to cancer remain largely unknown. Here, we investigated the role of SALL2 in cell proliferation by using mouse embryo fibroblasts (MEFs) derived from Sall2 mice. Sall2 MEFs exhibit enhanced cell proliferation and faster post-mitotic progression through G1 and S phases. Accordingly, Sall2 MEFs exhibit higher mRNA and protein levels of Cyclin D1 and E1. Chromatin immunoprecipitation and promoter reporter assays showed that SALL2 binds and represses CCND1 and CCNE1 promoters, identifying a novel mechanism by which SALL2 may control cell cycle. In addition, analysis of tissues fr...

Cancer is the second leading cause of death globally. One of the main hallmarks in cancer is the functional deregulation of crucial molecular pathways via driver genetic events that lead to abnormal gene expression, giving cells a selective growth advantage. Driver events are defined as mutations, fusions and copy number alterations that are causally implicated in oncogenesis. Molecular analysis on tissues that have originated from a wide range of anatomical areas has shown that mutations in different members of several pathways are implicated in different cancer types. In recent decades, significant efforts have been made to incorporate this knowledge into daily medical practice, providing substantial insight towards clinical diagnosis and personalized therapies. However, since there is still a strong need for more effective drug development, a deep understanding of the involved signaling mechanisms and the interconnections between these pathways is highly anticipated. Here, we perform a systemic analysis on cancer patients included in the Pan-Cancer Atlas project, with the aim to select the ten most highly mutated signaling pathways (p53, RTK-RAS, lipids metabolism, PI-3-Kinase/Akt, ubiquitination, b-catenin/Wnt, Notch, cell cycle, homology directed repair (HDR) and splicing) and to provide a detailed description of each pathway, along with the corresponding therapeutic applications currently being developed or applied. The ultimate scope is to review the current knowledge on highly mutated pathways and to address the attractive perspectives arising from ongoing experimental studies for the clinical implementation of personalized medicine.

Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF i...

Colorectal cancer (CRC) is one of the most common malignant diseases. Perturbation of the Endoplasmic Reticulum (ER) will lead to accumulation of malfolded or misfolded proteins in the ER lumen. This condition is referred to as ER stress. Three distinct arms of ER stress transducers are identified inositol-requiring protein-1 (IRE-1), activating transcription factor-6 (ATF-6) and protein kinase RNA-like ER kinase (PERK). XBP-1, a key regulator of the Unfolded Protein Response (UPR), was required for survival under hypoxia and critical for tumor growth. In this study, we investigated the role of X-Binding Protein (XBP-1) in CRC metastasis. Results indicated that, XBP-1 was expressed at high levels in metastatic and poorly differentiated tissue sample and a relatively low levels in moderately and well differentiated tissue samples. Moreover, XBP-1 was expressed in all cell lines of CRC examined in this study. Overexpression of XBP-1in SW480 cells promoted the invasion of cells, and this increase in tumor cell invasion was inhibited by inhibition of XBP-1 using small interfering RNA molecules (siRNA). In addition, results indicated that overexpression of XBP-1 in SW480 cells induced the level of Vascular Endothelial Growth Factor Receptor-2(VEGFR2) and inhibition of XBP-1 significantly decreased expression of VEGFR2, showing that XBP-1 is working upstream of VEGF-R2. This study demonstrated  that pretreatment of HCT116 cells with ER stress inducers such as Tunicamycin (TM) decreased 5-FU-induced-apoptosis. In conclusion, XBP-1 gene is overexpressed in CRC cells. Our results are strongly suggesting that XBP-1 promoted the invasion of colorectal cancer both in vitro and in vivo. Overexpression of XBP-1 cells enhanced VEGFR2 levels and could be responsible for CRC cell metastasis

The number of relevant and well-characterized cell lines and xenograft models for studying human breast cancer are few, and may represent a limitation for this field of research. With the aim of developing new breast cancer model systems for in vivo studies of hormone dependent and independent tumor growth, progression and invasion, and for in vivo experimental therapy studies, we collected primary mammary tumor specimens from patients, and implanted them in immunodeficient mice. Primary tumor tissue from 29 patients with breast cancer was implanted subcutaneously with matrigel in SCID mice, in the presence of continuous release of estradiol. The tumors were transferred into new animals when reaching a diameter of 15 mm and engrafted tumors were harvested for morphological and molecular characterization from passage six. Further, gene expression profiling was performed using Agilent Human Whole Genome Oligo Microarrays, as well as DNA copy number analysis using Agilent Human Genome CGH 244K Microarrays. Of the 30 primary tumors implanted into mice (including two implants from the same patient), two gave rise to viable tumors beyond passage ten. One showed high expression levels of estrogen receptor-α protein (ER) while the other was negative. Histopathological evaluation of xenograft tumors was carried out at passage 10–12; both xenografts maintained the morphological characteristics of the original tumors (classified as invasive grade III ductal carcinomas). The genomic profile of the ER-positive xenograft tumor resembled the profile of the primary tumor, while the profile obtained from the ER-negative parental tumor was different from the xenograft. However, the ER-negative parental tumor and xenograft clustered on the same branch using unsupervised hierarchical clustering analysis on RNA microarray expression data of “intrinsic genes”. A significant variation was observed in the expression of extracellular matrix (ECM)-related genes, which were found downregulated in the engrafted tumors compared to the primary tumor. By IHC and qRT-PCR we found that the downregulation of stroma-related genes was compensated by the overexpression of such molecules by the mouse host tissue. The two established breast cancer xenograft models showed different histopathological characteristics and profound diversity in gene expression patterns that in part can be associated to their ER status and here described as basal-like and luminal-like phenotype, respectively. These two new breast cancer xenografts represent useful preclinical tools for developing and testing of new therapies and improving our knowledge on breast cancer biology.

The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by performing genome-wide scans of CpG methylation in breast cancer samples with known expression-based subtypes. Unsupervised hierarchical clustering using a set of most varying loci clustered the tumors into a Luminal A majority (82%) cluster, Basal-like/ErbB2+ majority (86%) cluster and a non-specific cluster with samples that were also inconclusive in their expression-based subtype correlations. Contributing methylation loci were both gene associated loci (30%) and non-gene associated (70%), suggesting subtype dependant genome-wide alterations in the methylation landscape. The methylation patterns of significant differentially methylated genes in luminal A tumors are similar ...

Hedgehog (HH) signaling is involved in many physiological processes, and pathway deregulation can result in a wide range of malignancies. Glioma-associated oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1 cellular targets is quite limited. In this study, we identified multiple new GLI1 target genes using a combination of different genomic surveys and then subjected them to in-depth validation in human cancer cell lines. We were able to validate >90% of the new targets, which were enriched in functions involved in neurogenesis and regulation of transcription, in at least one type of follow-up experiment. Strikingly, we found that RNA editing of GLI1 can modulate effects on the targets. Furthermore, one of the top targets, FOXS1, a gene encoding a transcription factor previously implicated in nervous system development, was shown to act in a negative feedback loop limiting...

Identification of mutations as markers for early malignant transformation could be more appropriate not only for early diagnosis of cancer but could potentially influence treatment strategies in HNC,
since mutations in EGFR and Ras genes are closely associated with resistance to cancer treatment. Mutations in Ras, p53 (early), the gene of EGFR (in BCCs not detected), and HTERT promoter could be used as markers of cancer transformation. Mutations in p53 are detected early in PMDs, associated with high risk for early transformation into Oral SCC. Mutations in Ras are not detected in Potentially Malignant Disorders (PMDs), with exception of Actinic keratoses (AK), Keratoacanthomas (KA) and papillomas. Since increased expression of hTERT is an early event in the pathogenesis of hyperproliferative skin deseases, overexpressed hTERT is considered as a proproliferative (proinflammatory) marker, rather than cancer marker, in contrary to its mutations. Mutations in HTERT are detected in both Spinocellular carcinoma (SCC) and Basocellular carcinoma (BCC), UVsignature.
Increased expression mainly of MMP-9 and MT1-MMP (MMP-2), are now considered as markers for aggressive cancer phenotype in both cancers. Using EMT markers (vimentin, fibronectin, N-cadherin, vs, Ecadherin;
and transcriptional factors - Snail, Slug, Twist; HIF-1a, a-SMA), we could not differentiate late PMDs of early cancer lesions. These markers are useful for detection of aggressive alteration in tumour pathogenesis,
which is of importance when a surgical procedure is planned. COX-2 stain was highest in SCCs and aggressive BCCs. Increased expression of PKD1 was detected in BCCs in contrary to SCC. There is no currently data for the expression of PKD1 in PMDs, leading to SCC, nor for detected mutations in PKD1 gene in SCC and BCCs. PKD1 is upregulated and down-regulated in BCC and SCC, respectively. We speculate here that the molecular mechanism - increased NFKB-hTert-PKD1-NFKB-hTert, resulting in p16INK4a mutations and turn of PKD1 function, is connected with the progression of chronic inflammation in cancer development.

Dear Sir/Madam

We are currently hosting the Oncologist & Diagnostics Conference  which is going to be organized during August 28-30, 2017 Brussels, Belgium. With great pride and honour, we would like to invite you to participate in Oncologist & Diagnostics Conference in Brussels, Belgium

Kindly let me know about you interest toward participation as a Keynote, Speaker, Poster presentation, E-Poster and Video Presentation, delegate.
Kindly find the attached file for conference details

Kindly contact us for any sort of further assistance.
We sincerely hope that you will honour us by accepting our invitation

Regards
Celina Crystal
Manager of oncology and conferences
P 702 508 5200 Ext 8033
#cancerdiagnostics@cancersummit.org

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ConferenceSeries Ltd invites all the participants across the globe to attend the Oncologist & Diagnostics Conference slated on August 28-30, 2017 at Brussels, Belgium.

Cancer Diagnostics 2017 directs towards addressing main issues as well as future strategies of Cancer. This is going to be the largest and most promising international conference where the program includes Clinical Oncologists, Registered Nurses, Nurse practitioners and the entire medical team involved in patient care, researchers, professional, early career individuals and patient advocates who wish to learn principles of tumor immunology and immunotherapy well as decision makers will come to discuss and debate on various aspects of the challenges, risks and investment opportunities throughout the complete information of Cancers. Cancer Diagnostics 2017 will also provide the three days of discussions on methods and strategies related to management and quality improvement of Diagnostics device developing and Cancer Research and as well as to explore the new ideas and concepts on global scale and the topics include lung cancer, breast cancer, bone cancer, leukemia, blood cancer, cervical cancer, colon-rectum cancer, pediatric cancer, surgical cancer, Prostate cancer, thyroid cancer.

According to 2012 statistics approximately 14.1 million cases are reported and 8.2 million deaths are reported. Lung, Liver, Stomach and bowel cancers cause the most common deaths among the worldwide that accounts nearly half of all the cancer deaths. About 70% increase in the cases are to be expected over the next 2 decades. In males 5 most common sites of cancer are diagnosed in 2012 were lung, prostate, colorectal and liver cancers. In females 5 most common sites diagnosed were breast, colorectal, cervix, lung and stomach cancer. Nearly 60% of the world’s total new cases occur in the Africa, Asia and Central and South America regions. All over the world Denmark ranks 1st in the cancer deaths USA is accompanied next to it.

ConferenceSeries Ltd  which is comprised of 3000+ Global Events with over 600+ Conferences, 1200+ Symposiums and 1200+Workshops on diverse Medical, Pharmaceutical, Clinical, Engineering, Science, Technology, Business and Management field is organizing conferences all over the globe. It hosts numerous Cancer Conferences, Cancer meeting, global cancer conference, European Oncology Conferences, Surgical oncology like skin cancer conference, breast cancer conference, liver cancer conference, lung cancer meetings, and Oncology Conferences where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions and which helps get possibilities for treating the diseases with new era, technology and research.



Why Brussels???

Brussels, a region of Belgium comprising 19 municipalities, is a city of contrasts with enormous diversity, experiencing cool climates all throughout the year. Brussels is also becoming known as a mecca of style, art, and design having bilingualism of Modern French and Old Dutch.

Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients. Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of ≥20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)]. The miR-Score, using expression data of six microRNAs (miR-21-5p, -...

Protein kinase D1 (PKD1) posses proproliferative and antidifferentiative functions in human and mouse keratinocytes, prodifferentive function in hTert (N/Tert-1 or N-hTERT) keratinocytes, participate also in
wound-healing process in mouse epidermis. Loss of PKD2 enhanced keratinocytes-proliferative potential, while loss of PKD3 resulted in a progressive proliferation defect, loss of clonogenicity, and diminished tissue regenerative ability. This proliferation defect was correlated with upregulation of CDK4/6 inhibitor p15INK4B and induction of a p53-independent G1 cell-cycle arrest. Simultaneous silencing of PKD isoforms resulted in a more pronounced proliferation defect consistent with a predominant role for PKD3 in proliferating keratinocytes. There
are no data concerning regulation of the PKD1, 2 and/or 3 kinase expression in skin. The mechanisms regulating PKD1 expression are merely studied only in pancreatic and prostate cancer cells. In skin pathology, the kinase is with increased expression in psoriatic lesions and basocellular carcinoma (BCC) and downregulated in head and
neck spinocellular carcinoma (HNSCC). In the multistage mouse skin carcinogenesis model, the expression of PKD1 and CD34+ (cutaneous cancer stem-cell marker) are increased with increased expression of p53, p21, c-Myc, cyclin B, p-CDK1, and Cdc25A and inhibited activation of extracellular signal-regulated kinase 1/2 (ERK1/2), increased nuclear factor-kappaB (NF-kB), cyclic adenosine 3',5'-monophosphate-responsive element binding protein (CREB), and CCAATenhancer-binding protein (C/EBPs) activation by increased phosphorylation
of c-Jun-N-terminal kinase 1/2 (JNK1/2), p38 and phosphatidylinositol 3-kinase (PI3K)/Akt and by increased downstream target gene expression, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), ornithine decarboxylase (ODC), and vascular endothelial growth factor (VEGF). The hyperplastic and inflammatory responses in PKD1-deficient mice to topical phorbol ester were significantly suppressed suggesting involvement of PKD1 in tumor promotion (and inflammation). Consistently, when subjected to two-stage chemical skin carcinogenesis protocol, these mice were resistant to papilloma formation when compared to control littermates. There are no other data for PKD1 participation in inflammatory skin process and expression in other premalignant skin diseases. Recently, hotspot-activating mutation in PKD1, resulting in an p.Glu710Asp aminoacid
substitution, was detected in 73% of salivary Polymorphous low-grade adenocarcinoma (PLGA), associated with metastasis-free survival. Its increased expression is connected with late phases of malignant melanoma, associated with high metastatic potential. PKD1 participates in the pathology of inflammatory skin diseases and skin oncogenesis, but the mechanisms of regulation of its expression and action in skin in norm and in pathological processes are still unsufficient. PKD1 is upregulated merely in BCCs and in pancreatic cancer and downregulated
in HNSCC, prostate, breast gastric, and colon cancers.