Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 5th Asia-Pacific Summit on Cancer Therapy Brisbane, Australia.

Day 1 :

Keynote Forum

Veronica J James

Australian National University

Keynote: Highly accurate and much earlier tests for cancer must save lives

Time : 09:00-09:30

Conference Series Cancer Summit 2015 International Conference Keynote Speaker Veronica J James photo
Biography:

Veronica J James completed her PhD in Physics from the University of NSW in 1971. Working in crystallography, she published 40 papers on the molecular structures of small organic crystals, before moving into the fi bre diffraction studies of collagen and keratin. In this area she has carried out the diffraction study that produced the successful structure for hard keratin and also pioneered the fi bre diffraction diagnostic tests for breast, colon, prostate cancers and for Alzheimer’s Disease. She was awarded an OAM for her Phones for the Deaf Program and her Advanced Physics Programs in 1996

Abstract:

Such tests have been established using low angle X-ray diffraction of hair, nails or skin for a number of cancers and other diseases. In all such tests a change, specific to the cancer or disease is superimposed on the pattern for control samples. The results for all such tests is a sensitivity of 100%, since there have been no false negatives and a specificity >99% since there are less than 1% false positives. These results are much higher than for any other test to date.\\\\r\\\\n Since tests using transgenic mice have revealed that these tests can diagnose the relevant cancers and diseases much earlier than any other test, these false positives may not be false. Further to this should the cancer or disease be cured, the change disappears showing immediately whether the medical treatment has been successful. This talk will cover tests for prostate cancer and breast cancer. The results for prostate cancer indicate that this test can accurately determine whether the cancer is high or low grade and establish whether the cancer has invaded and by what method. The test for breast cancer accurately diagnoses all cancers but has different changes if the patient has a BRAC gene or not. Such tests can save lives.

Keynote Forum

Jagat R Kanwar

Deakin University, Australia

Keynote: Nanomedicine in Cancer: Nanotherapy and Nanodevices

Time : 09:30-10:00

Conference Series Cancer Summit 2015 International Conference Keynote Speaker Jagat R Kanwar photo
Biography:

Jagat R Kanwar is group leader and head of the Nanomedicine and Laboratory of Immunology and Molecular Biomedical Research has an international reputation in investigating fundamental and applied molecular aspects of cancer and chronic inflammation. Our nanomedicine laboratory of immunology and molecular biomedical research (NLIMBR) is discovering the novel and safe targeted nanomedicine based nano-nutraceuticals for cancers, autoimmune disorders and inflammatory diseases. We also vested the molecular diagnosis including role of a non-invasive exosomes in blood, inflammatory sites and cancer tissues. Our research focused on cancer and inflammatory autoimmune diseases aims to investigate the underlying mechanisms involved in apoptosis, autophagy and inflammation by targeting the production of cytokines, chemokines, oxygen radicals and matrix metalloproteinase. Our research also aims to investigate the nanotherapeutics encapsulating peptides, LNA modified aptamers/miRNAs/siRNA in vivo models. We have made significant progress in field of ocular drug delivery and microfluidic and Lab-on-a-Chip devices techniques for cancer cells as well as stem cell capture, disease specific biomarkers and exosomes. His publications more than 150 research papers and have added to the body of knowledge in the fields of nanobiotechnology, cancer gene therapy, cell biology and immunology. Kanwar research work has generated a total of 12 patent/PCTs. He is the member of various scientific committees and societies.

Abstract:

Drug resistance is a common drawback for most chemotherapeutic drugs and it promotes cancer survival and recurrence. The major protein that help a cell acquire MDR is P-glycoprotein (P-gp) and studies have showed that P-gp expression has been directly related to the degree of drug resistance in cells. P-gp also known as ABCB1 acts as a membranous molecular pump that effectively effluxes the chemotherapeutic drugs from within the cells. Overexpression of survivin in cancer cells has also been related to cause resistance to various chemotherapeutic compounds and therapies inhibiting survivin expression have shown sensitization of human cancer cells to various chemotherapeutic drugs such as docetaxel, paclitaxel and bortezomib. Studies have also shown that CD133 positive cancer stem cells resist chemotherapy which is mainly due higher expression of inhibitors of apoptosis protein (IAP) families and it has been also observed that the colony formation of CD133 positive cells is quite higher when compared to CD133 negative cells mainly due to overexpression of survivin. A major area of interest has come up using biomolecules which focusses on specifically target the diseased tissues. In our previous studies we have shown chimeric form of Fe-bLf (LNA-Nucleolin+EpCAM aptamer)-spions showed high specificity towards the tumour both in vitro and in vivo. In another study using ceramic polymer nanocarriers (ACSC NCs) we have shown that Fe-bLF(LNA-EpCAM aptamer+LNAsiRNA(survivin))-ACSC NCs were highly specific to tumour when compared to any other parts of the mice and the nanocarriers led to significant cytotoxicity specifically in tumour cells without harming the primary cells. We have also used novel oligo LNA siRNA (survivin) to target the nanocarriers and inhibit survivin expression in drug resistant cancer stem cells. Nanoparticles loaded with SR9 and LNAsiRNA-5-FU have been used in this study to target cellular survivin in colon cancer cells. Our results show that inhibition of survivin has a direct inhibitory effect on p-gp and CD133. The mechanism for explaining this phenomenon has also been investigated and a pathway has been proposed through which inhibition of survivin significantly lowers both p-gp and CD133 expression in colon cancer cells.

Keynote Forum

Izhak Haviv

Bar Ilan University, Israel

Keynote: Rational design of combination therapies and blockage of acquired targeted drug resistance

Time : 10:00-10:30

Conference Series Cancer Summit 2015 International Conference Keynote Speaker Izhak Haviv photo
Biography:

Izhak Haviv has completed his PhD at the age of 32 years from Weizmann Institute of Science and Postdoctoral studies from University of California, Berkeley (c/o Tjian lab, Head, HHMI). He is the Director of cancer research center of excellence in the Faculty of Medicine in the Galilee of Bar Ilan University, an academic clinical and translational research organization. He has an Affiliate Position in the University of Melbourne for 11 years and at Peter MacCallum Cancer Centre, Australia for 16 years. He has published more than 59 papers in reputed journals.

Abstract:

Recent successes of targeted drugs on end stage cancer patients highlight the value of mutation-based biomarkers for drug response. However, the impact of these drugs is often temporary and the patients progress to acquired resistance. A common mechanism of drug evasion involves feedback mechanisms that increase expression or phosphorylation-driven activation of an alternative oncogenic pathway. The objective of this work was to set up a streamlined methodology (kinome profiling, shRNA negative RNAi screens, evolution tracking etc.) for rational drug combination designs. It includes pre-clinical assessment of the novel drugs focused on cancer cases, refractory to biomarker predicted targeting and seeking combination therapies that would block the spontaneous drug evasion. We explored the efficacy of the combination approach on a panel of cancer patient derived xenografts in mice using tumor size or metabolic imaging as an end point. Each cancer case was subject to target somatic mutation screening which resulted in a targeted drug recommendation and then mouse groups were treated either with sequeincing-based therapy or with combination of these therapies with blockers of the suspected evasion mechanisms. As a blocker of the evasion mechanism and epithelial to mesenchymal transition, we characterized the utility of a molecule that leads to the destruction of IRS1/2 of the IGF1R pathway. Use targeted drugs such as Erlotinib, Zelboraf, Afinitorand Gleevec, all increase the attenuation of the cancer growth temporarily, followed by acquired resistance while inclusion of the IRS1/2 destruction lead to sustained efficacy and even lead to regression of the recurrent tumor mass.

  • Track 1: Cancer Cell Biology and Biomarkers
    Track 2: Advances in Cancer Detection, Imaging, Management and Prevention

Session Introduction

Pascal H G Duijf

University of Queensland, Australia

Title: Chromosome instability in cancer: Mechanisms and therapeutic consequences

Time : 10:45-11:10

Speaker
Biography:

Duijf obtained a PhD degree in Human Genetics from the Radboud University Nijmegen in the Netherlands. His postdoctoral studies at Memorial Sloan-Kettering Cancer Center in New York, NY, USA focused on how chromosome instability, the missegregation of chromosomes during cell division, contributes to cancer development and progression. In 2013, Dr Duijf established his independent research group at the University of Queensland Diamantina Institute and the Translational Research Institute in Brisbane, Australia. With an interest in breast and other cancers, his group studies chromosome instability in mouse models in order to develop new strategies to improve cancer diagnosis and treatment.

Abstract:

Cancer cells frequently missegregate chromosomes during cell division. This phenomenon termed chromosome instability leads to the formation of aneuploid cells i.e., cells with abnormal chromosome numbers. Chromosome instability is among the most malignant features of cancer cells because it can initiate cancer development, it accelerates cancer progression and it is an important mechanism for cancer cells to become resistant to cancer therapies. Even though more than a century has passed since we learned that chromosome instability is a common trait of tumor cells, we are now only beginning to understand how cancer cells become aneuploid. Work from our and other laboratories has provided important new insights into the molecular and cellular mechanisms of chromosome instability. Here, we will provide an overview of these mechanisms. We will also discuss the consequences of chromosome instability on the cellular and organismal levels as well as the profound impact of chromosome instability on the diagnosis and treatment of cancer.

Speaker
Biography:

Devathri Nanayakkara is a final year PhD student from Eskitis Institute for Drug Discovery, Griffith University. She is working on the deubiquitylating enzyme, USP9X under the supervision of Dr Stephen Wood.

Abstract:

Oral squamous cell carcinoma (OSCC) represents one of the most common cancers in the world. Identification of oncogenes, onco-suppressors and their molecular mechanisms is necessary to understand the process of oral tumorigenesis. Recently, deubiquitylase enzyme, USP9X, has been implicated as a tumor suppressor in oral carcinomas. This study aimed to further investigate USP9X’s role by knocking it down in four OSCC cell lines: SCC15, CAL27, FaDu and Detroit 562. Over 6 days all four cell lines displayed a reduction in cell numbers in the absence of USP9X and two of the cell lines, CAL27 and FaDu, revealed cell cycle alterations. USP9X regulates the mTOR pathway which plays a critical role in cell cycle progression. CAL27 and FaDu showed significant down regulation of the mTORC1 target, pS6 protein, in the absence of USP9X, probably causing the delay in cell cycle progression and decrease in cell numbers. In the other two cell lines, SCC15 and Detroit 562, differences in cell numbers were evident only after four days in culture. To determine if the delayed effect is due to terminal differentiation, levels of involucrin were assessed but no difference was observed. Interestingly, levels of MCL1, a pro survival protein and a USP9X substrate decreased in these cells after the fourth day. Hence the reduced cell numbers could be due to increased cell death. This study reveals that the absence of USP9X affects the proliferation/viability of OSCC cell lines. As previously shown, the roles of USP9X can be highly context specific and vary in early and advanced forms of oral cancers.

Kazuhiro Kaneko

National Cancer Center Hospital East, Japan

Title: Hypoxia imaging endoscopy equipped with laser light source

Time : 11:35-12:00

Speaker
Biography:

Kazuhiro Kaneko is working at National Cancer Center Hospital East, Japan

Abstract:

Recent endoscopy has evolved into image-enhanced endoscopy (IEE) such as Narrow Band Imaging and Blue Laser Imaging. IEE focused on increasing abnormal micro vessels in the surface of early cancers. It is difficult to recognize biological change, function and metabolism in cancer by observing the morphological features of the micro vessels. In contrast, hypoxia is one of the functional characteristics in cancer with strong association to the biological features. Therefore, hypoxia imaging was innovated to visualize directly the biological and functional changes in cancer. Aim: To evaluate the visualization of human early cancers in hypoxia imaging endoscopy prospectively. Methods: In endoscopic equipment, we utilized a difference of absorption between oxy- and deoxy-hemoglobin in visible light wavelength. The signals converted from laser light were calculated in oxygen saturation (StO2) by processor. Hypoxia imaging was obtained in real-time displaying two types of StO2 images. In the first in human clinical trial, patients who had been confirmed to have pharyngeal, esophageal, gastric or colorectal neoplasia by previous endoscopy were enrolled. To compare histologic findings to hypoxia imaging, all patients received endoscopic resection immediately after conventional and hypoxia imaging endoscopy. We determined the corresponding areas of neoplasia and non-neoplasia in the endoscopic images and obtained StO2 levels from the StO2 map. Results: Forty patients with neoplastic lesions in the pharynx, esophagus, stomach and colorectum were analyzed. The hypoxic area was completely corresponded to the portion of early cancer. Furthermore, 8 colorectal adenomas with histological low-grade atypia were also detected as hypoxia ranging from 3 to 10 mm in diameter. All esophageal cancers including 2 Barrett’s cancers were detected in hypoxia images. Median StO2 differences between neoplastic and non-neoplastic areas in the pharynx, esophagus, stomach and colorectum were -15.4%, -14.5%, -5.1% and -21.5% respectively. Furthermore, sensitivity of neoplasia defined as the proportion having correctly detected neoplasia, in the pharynx, esophagus, stomach and colorectum was 67%, 100%, 33% and 86% respectively. Conclusions: Hypoxia imaging with the laser endoscope enables us to visualize spatial and temporal information of hypoxic conditions in human tumors. Hypoxia imaging illustrates a novel aspect of cancer biology as a potential biomarker and can be widely utilized in cancer diagnosis.

Speaker
Biography:

Yuling Wang has completed her PhD in March 2009 from Chinese Academy of Sciences, China. After finishing her postdoc work in Purdue University, USA, she obtained an Alexander von-Humboldt Fellowship in German. Currently, she is working as an ARC DECRA fellow in Prof. Matt Trau’s group in Australian Institute for Bioengineering and Nanotechnology (AIBN), the University of Queensland. She has published more than 60 papers in reputed journals with an H-index of 26.

Abstract:

Surface enhanced Raman scattering (SERS) nanotags are a new class of labels for optical detection based on Raman scattering. Central advantages include the tremendous spectral multiplexing capacity for simultaneous target detection due to the narrow width of vibrational Raman bands, the need for only a single laser excitation wavelength to excite the Raman spectra of all SERS nanotags, quantification using the fingerprint intensity of the corresponding SERS nanotags; high photostability and optimal contrast by using red to near-infrared (NIR) excitation in order to minimize the disturbing auto fluorescence of cells and tissues. In this contribution, the innovative platform for rapid and multiple cancer biomarker detection such as epigenetic biomarker (DNA methylation) and protein biomarker (HER2) by using rational designed SERS nanotags will be discussed.

Speaker
Biography:

Izhak Haviv has completed his PhD at the age of 32 years from Weizmann Institute of Science and Postdoctoral studies from University of California, Berkeley (c/o Tjian lab, Head, HHMI). He is the Director of Cancer Research Center of excellence in the Faculty of Medicine in the Galilee of Bar Ilan University, an academic clinical and translational research organization. He has an Affiliate Position in the University of Melbourne for 11 years and at Peter MacCallum Cancer Centre, Australia for 16 years. He has published more than 59 papers in reputed journals

Abstract:

Somatic mutations emerge as superior biomarkers for rationalized drug selection in combating cancer. To trace the full cancer heterogeneity and detect mutations in cancer cells within DNA preparation that includes neighboring normal stromal cells, multiple target enrichment tools were development to allow sequencing of the most relevant area of the genome at the deepest possible. We assessed seven platforms for sensitivity and specificity over a common genomic area encompassing all frequently mutated exons of over 150 cancer causing genes; Fluidigm® Access Array, Raindance®, Life Technology® AmpliSeq-Ion Torrent, Illumina® TruSeq and Nextera rapid capture and Agilent® HaloPlex and SureSelect (all but the first sequenced on IlluminaMiSeq and HiSeq2500). Although these technologies were relatively comparable and capable of identifying clinically relevant mutations at high level of reproducibility and at least 90% specificity and sensitivity, one method emerged as superior. It had advantage when the cancer cells were a minority of the sample and had unique capability to detect gene fusions. Detecting low frequency mutations is important due to the dynamic selection that occurs when treating with anti-cancer drug. Therefore, we analyzed a number of samples from before and after acquired resistance and indeed found partial evidence to support the hypothesis that resistant cells are present in the onset of treatment. These results suggest that clinically driven tumor sequencing should read the samples at relatively high depth to allow the identification of rare resistant variants and attempt to treat in accordance to their presence in the first line of treatment

Veronica J James

Australian National University, Australia

Title: Highly accurate and much earlier tests for cancer must save lives

Time : 12:50-13:15

Speaker
Biography:

Veronica J James completed her PhD in Physics from the University of NSW in 1971. Working in crystallography, she published 40 papers on the molecular structures of small organic crystals, before moving into the fi bre diffraction studies of collagen and keratin. In this area she has carried out the diffraction study that produced the successful structure for hard keratin and also pioneered the fi bre diffraction diagnostic tests for breast, colon, prostate cancers and for Alzheimer’s Disease. She was awarded an OAM for her Phones for the Deaf Program and her Advanced Physics Programs in 1996

Abstract:

Fibre Diffraction has far more to offer than diagnostic tests for just breast and prostate cancers. Using hair and nail samples, a test for Alzheimer's Disease shows the presence of this disease before any damage has occurred to the brain, gaining time for treatment. In addition to this, changes have been found using hair and nail samples that specifically diagnose colon cancer, adeno lung cancer and insulin dependent diabetes. For skin samples, melanoma and bowel cancer can also be diagnosed. If more than one cancer is present, changes in the structure for both appear. A study of breast tissue has elucidated the 4 changes in breast tissue surrounding a ductal carcinoma, which precede the cancer itself. Such changes are visible in pathology slides. A study of colon tissue has provided reasons behind the reappearance of such cancers 2 years after removal, more than 50% of such repeat cancers being terminal. Sixty years after the first diffraction pattern was obtained our crystallographic studies have also provided a structure for hair which satisfies all known data. This structure combines sets of helices within helices, the outermost set forming 8 tetramers that give rise to the 7 lattices that define the structure.

  • Track 3: Organ-Specific Cancers and Cancer Genetics
    Track 4: Anti-Cancer Drug Discovery and Development
Speaker
Biography:

Rupinder K Kanwar completed her PhD from PGIMER, India. Since then she has worked in India, New Zealand and Australia, in a variety of positions supporting and building new research programs related to interdisciplinary research, international collaborations and large-scale initiatives ranging from biomedicine to nanomedicine. She has 15 years’ experience in drug discovery targeting cancer and chronic inflammation, and delivered both academic and industry-oriented research with 75 peer reviewed publications. Dr Kanwar is a key inventor in more than 20 published and live patents/ applications. Her current research focuses on targeting molecular pathogenesis of chronic inflammatory diseases and cancer with nanodrug and nanodiagnostic developments. At Deakin University, she is providing leadership to her research team on deciphering novel molecular targets for protein biodrugs to treat cancer and cardiomyopathy. She serves as an editorial advisory board member and reviewer of several international journals. Dr Kanwar has been invited as a speaker, and chair in national & international conferences, and her research presentations won awards at conferences

Abstract:

Survivin is a 16.5 kDa protein of the inhibitor of apoptosis proteins (IAP) family. It has been detected in almost all types of cancer and is a key target for cancer therapy. The overexpression of survivin in tumors is associated with enhanced tumor cell survival and growth, poor prognosis, drug resistance, radioresistance, angiogenesis and regulating metastasis. Several therapeutic strategies to target the expression and function of survivin at various levels have been employed. However, very few have reached to the clinical trial stage and currently, there is a void for promising clinically safe survivin targeting agents (s). More recently, we have identified bovine milk derived lactoferrin (bLf)’s unprecedented survivin targeting activity both at the gene transcription and protein translational levels. Lactoferrin (Lf) is a naturally occurring iron-binding glycoprotein. It is widely known for its multifunctional nature, and is present in external mammalian excretions including tears, sweat and most importantly milk and colostrum. bLf’s roles in iron homeostasis, organ morphogenesis, and bridging innate and adaptive immune functions, have resulted in its potential applications in the medical field, along with its wide use as a current nutraceutical and a safe food supplement. bLf has a clinically proven safety profile. More importantly, based on animal feeding studies and the success of human clinical trials in cancer patients, bLf has gained significant attention for its potential as a safe anti-cancer chemopreventive and biodrug. Through preclinical studies and clinical trials, we and others have shown that bLf in its native form, and in iron saturated form (Fe-bLf) can not only inhibit tumor development but also reduce growth and metastasis of solid tumors. Earlier, bLf’s anti-cancer activity was reported due to its immunity boosting activities and activation of cancer cell specific apoptotic mechanisms, through the modulation of both the extrinsic and intrinsic pathways. The capacity of safe and non-toxic bLf to target survivin expression and modulation of cancer cell growth and apoptosis highlights an exciting potential for bLf as a much needed anti-survivin biodrug. The novel findings of the study with promising results on anti-cancer efficacy will be presented in the meeting.

Juliana antonipillai

Victoria University, Australia

Title: Inhibition of LIM kinase inhibits cancer growth

Time : 14:25-14:50

Speaker
Biography:

Juliana Antonipillai is a lecturer in the College of Health & Biomedicine. She specialises in cancer and cardiovascular biology. Prior to joining Victoria University, Juliana was an academic researcher for 12 years at several medical research institutes and hospitals in Melbourne and the USA. In the last five years her research has focused mainly on how LIMK regulates platelet function in humans and mice, and on the role of LIMK in cancer metastasis, using a variety of small molecule LIMK inhibitors. She demonstrated that these inhibitors inhibit the proliferation of human breast cancer cells in 2D and 3D cultures. She also contributed to a collaborative study showing the effect of a new LIMK inhibitor drug, Pyr1, on cancer cell growth in vitro and in mice.

Abstract:

LIM kinase (LIMK) regulates actin cytoskeleton via inactivation of an actin depolymerising factor cofilin and involves in cell motility, invasion and migration. Metastasis is the major cause of death in cancer patient and the factors that regulate migration and invasion considered to be a good therapeutic target for metastatic disease. We investigated the consequences of LIMK inhibition on growth and metastasis of humans and mouse cell lines and tissues with number of LIMK inhibitors. LIMK activity was reduced in tumor cells by expression of dominant-negative LIMK1 by RNA interference or with a selective LIMK inhibitor. The extent of phosphorylation of the LIMK substrate, cofilin of proliferation and invasion in 2D and 3D culture and of tumor growth and metastasis in mice were tested. Inhibition of LIMK activity efficiently reduced the pro-invasive properties of tumor cells in vitro. Tumors expressing dominant-negative LIMK1 grew more slowly and were less metastatic in mice. Our findings with number of cell permeable LIMK specific inhibitors and SiRNA suggest that LIM kinase functions as a signaling node that controls actin dynamics. LIM kinase may therefore represent a targetable enzyme for cancer treatment.

Speaker
Biography:

Selina Sutton completed her PhD at the University of New South Wales in Sydney, Australia. Presently, she is a Post-doctoral researcher at the Children’s Cancer Institute. She has presented her research at numerous conferences including an oral presentation at the annual Paris Melanoma Conference in 2014. She is interested in discussing research collaboration.

Abstract:

The discovery of BRAF inhibitors has revolutionized therapy for the 50% of patients with BRAFV600 mutant melanoma however BRAFWT melanomas have few effective therapies. The oncogene NRAS is activated by mutation in 15-20% of melanomas and has limited therapeutic options. Among 24 hit compounds from our recent drug screen for small molecules that enhanced the cytopathic effects of histone deacetylase inhibitors, we identified compound 012 (C-12) which unexpectedly had significant single agent activity on melanoma cell viability with limited toxicity against normal human fibroblasts. Importantly, when combined with the BRAFV600 inhibitor, vemurafenib, C-12 synergistically increased vemurafenib potency in 5 of 6 BRAFWT melanoma cell lines (Combination Index: CI<1) and dramatically reduced colony forming ability (P<0.0001). Mechanistically, combination vemurafenib+C-12 markedly increased a growth suppressor, tripartite motif (TRIM) 16 protein level and knockdown of TRIM16 in melanoma cells significantly reduced vemurafenib+C-12 induced growth inhibition suggesting that the combination exerted synergistic anti-cancer effects by inducing TRIM16 expression resulting in consequent growth arrest. Microarray analysis revealed an increase in cholesterol biosynthesis suggestive of a response to decreased intracellular cholesterol with combination treatment. Synergy studies between cholesterol inhibitors, lovastatin & U18666A and vemurafenib revealed significant synergy preferentially targeting BRAFWT melanoma in like manner to C-12. Taken together, we have identified a novel compound which works synergistically with BRAF inhibitor as an anti-cholesterol drug and specifically targets BRAFWT melanoma cells. We have further shown that statins combined with vemurafenib have significant anti-tumour activity in BRAFWT melanomas, suggesting a novel therapeutic approach.

Ram Kumar Singh

Advanced Centre for Treatment Research and Education in Cancer, India

Title: IGF-1R: A key linker between chemoresistance and cancer stem cells in epithelial ovarian cancer cells

Time : 15:15-15:40

Speaker
Biography:

Ram Kumar Singh has completed his masters in life sciences with distinction. He qualified national level exams GATE and CSIR-UGC NET and availed five years scholarship to pursue his Ph.D. Currently he is at the verge of completion of Ph.D. In his entire tenure of Ph.D. programme he has published in high impact peer reviewed journals: one first author paper in Cancer Letters, and two co-author papers in IJBCB and CELL, one book chapter in Engineering in Translational Medicine (Springer publication). He has also presented his work in various national and international conferences

Abstract:

Generation of chemoresistance and tumor relapse is major therapeutic barriers for successful treatment of ovarian cancer. According to the current notion, a small population of cells (Cancer Stem Cells or CSCs) residing in the tumor bulk aids in drug resistance and tumor relapse. To understand these associations, we developed several drug resistant models against cisplatin, paclitaxel and cisplatin + paclitaxel using A2780 cell line and further classified them into early resistant and late resistant stages. We have previously shown that these early resistant cells possessed high levels of Insulin like Growth Factor 1-Receptor (IGF-1R) expression and Picropodophylin (PPP), an IGF-1R inhibitor potentiated maximal reversal of resistance at early stages (Singh et al, 2014, Cancer Letters). In the present study, an enrichment of CSC like phenotype (biomarker-CD44 & CD133, self-renewal, and Side Population/SP) was observed with gradual increase in resistance. Expression of Oct4, Sox2 and Nanog increased from sensitive to early stage of resistance, which further remained constant at late resistant stages. Non-invasive bioluminescence imaging revealed that SP cells isolated from early resistant stages possessed higher tumorigenic potential than SP cells isolated from the late resistant stages. Interestingly, inhibition of IGF-1R with PPP abrogated the expression of stemness genes and spheroid formation. However silencing of Oct4 and Sox2 did not affect IGF-1R expression indicating IGF-1R as an upstream regulator of these stemness genes. Thus our present data suggests that IGF-1R is a key molecule that governs the cross talk between cancer stem cells and acquired chemoresistance in epithelial ovarian cancer.

Speaker
Biography:

Chia-Ning Shen received his PhD degree in 2002 from the Department of Biology & Biochemistry, University of Bath , United Kingdom. And then, from 2002-2004, Dr. Shen had his postdoctoral training at the Center of Regenerative Medicine, University of Bath, United Kingdom. Since 2004, Dr. Shen joint the Genomics Research Center of Academia Sinica. Dr. Shen is now an Associate Research Fellow and Deputy Director at Genomics Research Center of Academia Sinica, Taipei, Taiwan. He is also serving as Adjunct Associate Professor at National Yang-Ming University, Taipei, Taiwan

Abstract:

Acinar-to-ductal metaplasia (ADM), an inflammatory lesion associated with replacement of acinar cells by tubular complexes is thought to represent a condition with increased risk of neoplasia. However, the direct evidence linking acinar-to-ductal metaplasia and development of pancreatic neoplasm is still lacking. Glucocorticoid-mediated signaling pathway is known to be a part of the feedback control machinery of immune system that acts to suppress excessive immune activity. In the present study, we explored the role of GR in development of ADM and pancreatic intraepithelial neoplasia (PanIN) in mice with pancreatitis. We initially identified that evaluated levels of activated glucocorticoid receptors (GR) were observed in patients of chronic pancreatitis and pancreatic ductal adeno carcinomas (PDAC). Utilizing mice conditionally expressed KrasG12D in acinar cell with or without loss of GR, we demonstrated that GR activation was required for generation of metaplastic ductal lesion and development of pancreatic intraepithelial neoplasia (PanIN) in mice with experimental pancreatitis. Administration of dexamethasone,a potent synthetic glucocorticoid was sufficient to induce development of PanINs and PDACs in KrasG12D mice that harbored single-allele deletion of p53. We further revealed that non-genomic activation of GR was a key action that led to evaluate c-Src signaling and trigger a pathological threshold of Ras activity necessary for neoplastic transformation. In contrast, treatment of dasatinib, a Src kinase inhibitor suppressed development of PanINs and PDACs induced by dexamethasone. Importantly, Cre-lox based lineage-tracing mice was applied and identified that GR activation directly transformed GFP-tagged KrasG12D-expressing acinar cells to tumorigenic cells. The findings explained why inflammatory ductal reprogramming predisposes to development of pancreatic neoplasm.