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the 27th annual convention of the iacr – a report

The 27th Annual Convention of the IACR – A Report by Dr. Ujjwala M. WarawdekarGenetic Engineering Dept.
ACTREC, Tata Memorial Centre,Navi Mumbai.
The 27th Annual Convention of the IACR named IACRCON –2008 was held at the GCRI, Ahmedabad between the 7th and 9th February, 2008. It coincided with the celebrations of the silver jubilee of the Department of Cancer Biology of the GCRI and the birth centenary year of Dr. T B Patel, the Founder Director whose guidance and efforts have helped establish the Institute to its present stature. The Convention was spaced out between the first and the third day with a total of eight sessions covering various areas of Cancer research, basic and translational, with a global representation. The International Symposium on Frontiers in Functional Genomics between these two days was the high point of the Convention and featured talks on approaches and clinical trials applying latest technologies, to study, understand and treat Cancer.
Honorable Shri Jayanarayan Vyas, Health Minister of the state of Gujarat and
dignitaries from the Health Ministry formally inaugurated IACRCON- 2008.
Dr. B C Das delivered his first Presidential Oration, making it his second, in the history
of the Association. He spoke on Gene, Environment and Cancer and began with the
profound statement that, "every ailment in humans, except trauma, has a genetic basis."
And eruditely continued, to explain the important role of environment besides the genetic
component in the manifestation of the disease, Cancer. The talk reiterated to the experts
in the field that for understanding the biology as well as the treatment of the disease, a
holistic approach with emphasis on the gene environment interaction is of utmost
importance Finally, he introduced the relatively new discipline, Environmental Genomics
and Prevention, in the context of Cancer. It was a very thought provoking talk which
emphasized the fact that Cancer is a multifactorial disease, and so far, scientists have
been focusing on the genetic and environment components in isolation, and it is time now
for a convergent approach, like identifying new functional polymorphisms of genes that
influence an individual's risk of developing cancer
The first session was on Translational Research chaired by Dr. Vinay Puduvalli
[MDACC, USA] and Dr. CFM Sier [LUMC, The Netherlands]. There were four invited
speakers and the talks spanned from targeted therapy to chemoprevention. Dr. Jayaram
Hiremagalur
[IUSM, USA] spoke on Targeted Chemo-Gene therapy for Colorectal
Cancer with possibilities of a highly effective therapy with low toxicity. Colon Cancer is
the third most common cause of death from cancer. There are several drugs available in
the clinic, which inhibit the enzyme IMPDH and bring about cell death. One such drug is
Tiazofurin, which is converted by the enzyme NMNAT to its active form TAD, a potent
inhibitor of IMPDH resulting in cancer cell death. He spoke about preclinical studies
carried out by over expressing NMNAT and specifically targeting this enzyme to the
colorectal cancer cells by virtue of the folate receptors, which are over expressed in
cancer cells. Also, another aspect of this therapy described, was increasing the delivery of
the drug, tiazofurin by encapsulation in folate-tethered liposomes. Dr. Subbarayan
Pochi
[Roswell Park Cancer Institute, USA] spoke on the use of Arsenic Trioxide
(As2O3) as a chemosensitizer of 5FU. An effective agent used in many alternate
medicinal systems As2O3 could overcome the chemoresistance that occurs with 5FU. 5
Fluoro Uracil is a major anti neoplastic agent used in treating many solid tumours. The
drug competes with the natural substrate dUMP for the enzyme Thymidylate synthase in
DNA synthesis thus eventually arresting cell growth. Due to the auto regulatory
properties, TS levels increase in tumour cells resulting in chemoresistance. The
observation that As2O3 reduces chemoresistance by lowering the levels of TS in cultured
human colorectal cell lines in vitro and that As2O3 transiently reduced TS expression in
the PBMC of patients led to several cell proliferation assays to test the cytotoxic effects
of As2O3 .On the basis of the in-vitro studies a Phase I clinical trial for As2O3 along with
the 5FU regimen was initiated and data showed that 0.15mg/kg of As2O3 and 2600mg/
m2of 5-FU regimen was safe. The results showed that As2O3 effectively suppressed TS
level by 70% to80%. A very relevant and important question that came up during the
discussion was about the mechanism of the down regulation of TS. Mechanistic studies
delineating the down regulation of the enzyme can be carried out.
Dr U. Manne [UAB, USA] spoke on ‘Molecular Advances in Colorectal Cancer with the
need to Educate Researchers and Clinicians for improved Patient Care'. In his talk, he
spoke of the importance of p53 as a predictor of survival with importance to the location
of the tumour either proximal colon, distal colon or rectum and the ethnicity of the
patient. Gene sequencing analyses of p53 revealed that the proximal tumours in
Caucasians exhibited a higher incidence of missense point –mutations in the DNA
binding domains of p53 than tumours from other locations in Caucasians and tumours
from all anatomic sites from African-American population. With examples of differences
in SNP of p53, decreased expression of Bcl-2, increased expression of p27 in different
patient ethnicity and the prognosis of the disease he emphasized that understanding
differences in patient race/ethnicity, tumour location with molecular, clinical and
pathologic factors will facilitate personalized medicine.
The last talk of the session was delivered by Dr. Buttar [Mayo Clinic & Mayo
Foundation, USA] on GI Cancer Chemo prevention and he elaborated on the need for a
well-defined chemoprevention strategy to reduce the anticipated burden of GI cancers in
the developing as well as the developed countries of the world.
During the lunch hour, posters for the IACR Poster awards, Rajnikant Baxi and
Rambhau Kulkarni, and the non –award posters [1-32] were viewed. The award posters
were displayed for all the three days.
Post lunch there were two simultaneous sessions, Cytogenetics and Cancer chaired by
Dr. Siddharth Adhvaryu [USA] and Dr. Thomas Liehr [Germany] and Cell Signaling
and Cancer
chaired by Dr. Shubhada Chiplunkar [India] and Dr. Bharat Joshi [USA]
The session on Cytogenetics and Cancer began with the talk on ‘Genetic Testing for
Hereditary Colorectal Cancer: Current Status and Future Direction' by Dr. Patrick
Lynch
[MDACC, USA]. He spoke about the necessity of genetic testing for determining
the basis and improving management of the disease, even though the percentage
constituting both the FAP and HNPCC due to heredity is small. Mentioned limitations of
APC testing in India, and probably overcoming these by developing Reference labs for
APC testing.
Dr. Stefan Bohlander [University of Munich, Germany] gave a talk entitled‘ Defining
an 86-Probe Set Gene Expression Signature Predicting Survival in Acute Myeloid
Leukaemia with Normal Karyotype'. He described survival of AML patients according to
Cytogenetic subgroups. The subgroups described were AML-M2, AML-M3 and AML-
M4. Also looked at AML patients with submicroscopic mutation. Developed a survival
specific gene signature of patients with AML and submicroscopic mutation and looked at
Relapse free survival and Overall survival. The 86-probe set correlated with Overall
survival and some of the top ranking genes identified in the study were SOCS2,
KIAA0125, GUCYIA3, GPR5, GPR6. The 86-probe set corresponds to a 66-gene
signature. Groups in other continents have validated this signature.
Dr. CK Panda [Chittranjan National Cancer Institute, India] spoke on candidate tumour
suppressor genes identified by association with the development of early dysplastic
lesions of head and neck. Candidate genes like LIMD1, LTF, CACNA2D2, which were
identified by deletion mapping and promoter hypermethylation analysis and their
alterations and association with development of moderate dysplastic lesions, progression
of the disease and the disease outcome was discussed.
The session on Cell Signaling and Cancer began with the talk by Dr. Ajit Verma
[Univ. of Wisconsin, USA] on Protein Kinase C epsilon being a master switch in the
induction and progression of Human cancers. PKC interacts with Stat 3.The physical
interaction was shown in various human cancer cell lines using reciprocal
immunoprecipitation and blotting experiments. PKC activates Stat3, which is linked to
induction, progression and invasion of human cancers. PKC and Stat3 may be potential
molecular targets for the prevention and treatment of various human cancers. The second
talk by Dr. Gopal Kundu [NCCS, India] was on the diagnostic and therapeutic
significance of Osteopontin. His group has shown, with in-vitro studies and in animal
models, that Osteopontin regulates a series of signaling cascades through activation of
various kinases and transcription factors that lead to changes in expression of genes
important for angiogenesis and tumour progression. They have shown that OPN is
expressed in several tumour types and the level of expression could be correlated to the
staging of the tumours in breast and prostate cancers, thus opening the possibility of a
targeted therapeutic approach.
Poster viewing, which began during lunch continued over tea and the interaction and
scientific discussion, was stimulating and refreshing.
Finally for the day, there were two simultaneous sessions; Molecular Mechanisms of
Carcinogenesis
chaired by Dr. P. Kondaiah [IISc, India] and Dr. Rakesh Singh
[UNMC, USA] and Tumour Biology chaired by Dr. Surekha Zingde [ACTREC, India]
and Dr. Rita Mulherkar [ACTREC, India].
The session on Molecular Mechanisms of Carcinogenesis commenced with the talk by
Dr. Vinay Puduvalli [MDACC, USA] on Multidisciplinary Clinical and Translational
Research in Glioma. The treatment of any tumour would necessitate the understanding of
the biology of the tumour. In the context of Gliomas, which has a grim prognosis, the
targets could be proliferation, angiogenesis, invasion, genetic alterations, resistance to
cell death and drug resistance. Discussed systemic therapies using EGFR, VEGFR and
MMP inhibitors. Also, Chemo radiation therapy with temozolomide in the context of
MGMT promoter methylation, which resulted in improved survival for a subset of
patients with glioblastoma. He spoke of simultaneous targeting of multiple pathways and
strategies to develop a novel trial design. As there are non-responders to any therapy,
complementing the clinical strategies, studies on genetic and epigenetic regulation of
gliomagenesis, identification of genetic signatures that correlate with prognosis and
characterization of stem –like cells in gliomas is also being done. Dr. Subrata Sinha
[AIIMS, India] gave a talk entitled, "Genomic instability in Glial tumours: Global
changes versus Phenotypic Selection" and discussed studies carried out on high and low
grade primary human glial tumours, both for molecular indicators of generalized
instability as well as locus specific changes that influence the tumour phenotype Dr.
Vijay Kumar
[ICGEB, India] spoke on "Cyclin D1 is a mediator of cell cycle arrest
induced by genotoxic agents" and presented data showing that hydroxyurea brought
about growth arrest by destabilization of cyclinD1 in addition to being a ribonucleotide
reductase inhibitor. The antimetabolite, hydroxyurea induced degradation of cyclin D1,
which was by virtue of its phosphorylation at Thr286 by GSK –3 beta. Inhibition of
GSK-3 beta or the over expression of the mutant form of cyclin D1 conferred stability to
cyclin D1.Also, the over expression of the mutant cyclin D1 could compensate for the
growth arrest induced by hydroxyurea. These conditions also resulted in a rapid
inactivation of the enzyme Akt and the expression of its constitutively active form could
overcome the growth arrest induced by hydroxyurea and stabilize cyclin D1. Dr. Vijay
Laksmi Kumar
[AIIMS, India] gave a talk entitled "Immunoreactive Estrogen Receptor
and its E-Domain Variants in Breast Cancer". She presented data from a clinical study in
which the Estrogen receptor level was determined in breast tissue samples by ELISA and
analysis for splice variants of hormone binding was carried out by RT-PCR and showed
that the estimation of ER levels combined with composite analysis of ER variants may be
a better prognostic marker for breast cancer.
The session on Tumour Biology began with the talk by Dr. Kishore Amin [ACTREC,
India] entitled, "Interleukin-8 Expression in Urine of Patients with Superficial Bladder
Cancer after BCG Instillation: Mechanism of Action" The next talk by Dr. Bidhut Roy
[ISI, India] entitled "Mitochondrial DNA Polymorphisms and Mutations in Oral Cancer
and Leukoplakia" dealt with analysis of data obtained from a population based study on
polymorphisms and mutations in mitochondrial DNA and included a large cohort of
controls, oral cancer patients and individuals with leukoplakia. The genotyping of the
samples was done with four mitochondrial loci; two U- haplogroup markers and one each
of N and M haplogroup marker. The N and M markers were marginally whereas one of
the U markers was significantly over represented in cancer. This over representation was
more pronounced among smokers and not found among tobacco chewers. Also, the
4977bp deletion was observed in leukoplakia whereas the D-loop mutations were
detectable only in cancer tissues suggesting that 4977bp deletion is an early event while
the D-loop mutation is a late event in carcinogenesis. The last talk of the session was by
Dr. T. S. Ganesan [Amrita Institute of Medical Sciences & Research Centre, India]
entitled,"RPS6KA2, A putative tumour suppressor gene at 6q27 in Sporadic Epithelial
Ovarian Cancer".
The second day of the Convention saw the International Symposium on Frontiers in
Functional Genomics
. The first session was chaired by Dr. Pankaj Shah [GCRI, India]
and Dr. BC Das [ICPO, India]. The keynote Lecture was delivered by Dr. Martine
Piccart [Jules Bordet Institute, Belgium] with a very reflective title 'Translational
Research: The Rosetta stone of Breast Cancer'. She emphasized on the importance and
need of Translational Research to offer personalized therapy and presented micro array
data from different groups, which showed that breast cancers could be grouped to at least
4 composite expression profiles: basal-subtype, erbB2 subtype, luminal B and A
subtypes. The new genomic grade index developed would allow tailored clinical trials
and probably lead to the discovery of new relevant drug targets. The development of
multi-gene prognostic signatures and multi-gene predictive signatures would ultimately
lead to improved disease management and better patient care which is the major goal for
clinicians as well as cancer researchers. The next talk by Dr. Nees Mattthias [VTT
Medical Biotechnology, Finland] was entitled, "Canceromics: Functional Insights by
Integration of Genomic Technologies" and deliberated on the large microarray data flood
that has contributed immensely to the understanding of malignant diseases and to some
extent allowed outcome predictions and prognosis. The emphasis of the talk was that the
vast data generated should be utilized to develop new drug targets and therapies,
understand the pathways and altered mechanisms in Cancer to achieve improved
therapeutic strategies. The next talk entitled, "Structural Genomics: The ultimate
approach for rational drug discovery and support for functional genomics." was by Dr.
Lundstrom Kenneth
[KL International Bio Consulting, Switzerland]. He described the
value of the structural information of a protein and that this could be used for improved
drug potency, reduction in side effects and can be obtained from information deposited in
public databases. There are structures of 200 membrane proteins and 35,000 soluble
proteins available. The tools required are Bioinformatics, clones that are commercially
available, but the low success rate for structure determination of membrane proteins is
due to difficulties in the areas of over expression, purification and crystallization of
recombinant proteins. The next talk was by Dr. Sharon Ross [NCI, USA] on,
"Nutritional Genomic Approaches to Cancer Prevention". It was an interesting talk on
nutrigenomics, and the interplay between genes and diet could possibly identify
modifiable molecular targets for preventing, delaying or reducing the symptoms of cancer
and other chronic diseases.
Posters 33-64 were viewed along with the mid-morning coffee break. They were displayed through the day and were discussed by the participants during the other breaks too. The Functional Genomics Session II chaired by Dr. Kenneth Lundstrom [KL Int.,
Switzerland] and Dr. Sharon Ross [NCI,USA] began after the mid–morning coffee
break with the talk on, "Principles of Micro array Analysis" by Dr. Wiltgen Marco.
[Medical University of Graz, Austria]. He discussed the technique and the methods of
analyzing the vast data that is available from a micro array and also the possible
applications of this technique. This was followed by a talk on "Signaling Networks in
Breast Cancer –New Targets for Hormone Therapy" by Dr. Adriana Stoica [Lombardi
Cancer Center, USA] She discussed theMCF-7/Akt1 breast cancer model that was
developed earlier and now used to identify patterns of genes regulated by estradiol and
Akt1 in the presence or absence of antiestrogens and AG 825. From the data generated
and using a software program, two molecular signaling networks with estrogen and Akt1
regulated genes downstream of ErbB2 have been constructed. These newly identified
genes may provide new therapeutic targets and / or predictive clinical markers.
Dr. P. Kondaiah [IISc, India] delivered a talk on, "Use of Microarrays to identify
Glioma Biomarkers with Prognostic and Therapeutic Value". He presented micro array
data on astrocytomas of different grades and showed that there are several novel genes,
which are differentially expressed between the lower grades [II/III] and glioblastoma
multiforme [GBM, Grade IV]. Several genes of the Notch signaling pathway were found
to be differentially expressed. IGFBP2, FABP were over expressed in GBM. GADD45
alpha was shown to be a prognostic marker. Similarly, NMPRTase was shown to be over
expressed in GBM and could be a potential serum marker. He further assessed it for a
prognostic marker, with poor prognosis when over expressed, but the data was not
significant. The information generated could form a basis for building
diagnostic/prognostic gene signatures in glioma progression and novel therapeutic
targets.
In the same session Dr. Bhavana Dave [UNMC, USA] spoke on the use of molecular
cytogenetics, and techniques like FISH, multicolor FISH and array CGH for detection
and screening of chromosomal alterations in lymphomas, in her talk "Cytogenetics to
Genomics: Approaches in Lymphoma Diagnosis and Research". She also reiterated the
importance and the necessity of techniques like aCGH especially in identifying and
distinguishing between Burkitts and high-grade Diffuse Large B cell Lymphomas for
treatment and better clinical management.
It was a day devoted to Functional Genomics and post lunch Session III was chaired by
Dr. Nees Matthias [VTT Medical Technology, Finland] and Dr. Marco Wiltgen
[Medical University of Graz, Austria].
Dr. Franz Bosch [University of Heidelberg, Germany] began with the talk entitled
"Towards Proteomics based Classification of Head and Neck and Oral Cancer". He spoke
about the SELDI-TOF MS as an alternate fast and high throughput proteomics platform
and its usefulness for tissue protein profiling. Data generated from analyses of large
collections of biopsies of healthy squamous mucosa, tumour surrounding mucosa and
HNSCC/OSCC was discussed. Several candidate biomarkers like S-100 proteins, the
cysteine proteinase inhibitors and defensins have been identified by mass spectrometry
and alterations in expression were confirmed by cDNA micro array analysis and
validated by immunohistochemistry using tissue micro arrays.
The next talk by Dr. Surekha Zingde [ACTREC, India] was on ‘Tissue and
Immunoproteomic Approaches for Oral Cancer' wherein she discussed the 2DE-MS
approach used to study the differential protein expression from micro-dissected tumour
and normal tissue of the gingivo- buccal complex.14-3-3 protein has come up as one of
the key differentiator molecule in the transformed epithelium and could be a potential
therapeutic target.
In the same session, Dr. Thomas Liehr [Inst. Of Human Genetics and Anthropology,
Germany] spoke on Molecular Cytogenetics in Tumour cells and emphasized on the
importance of cytogenetic analyses with FISH and mFISH in studying chromosomal
aberrations and rearrangements in cancer research.
The last talk of the session as well as the one-day symposium was on the ‘Prognostic
value of Matrix Metalloproteinases in Gastro-Intestinal Neoplasia' by Dr. CFM Sier
[LUMC, Netherlands] where he discussed the detection of MMPs for prognostic purposes
with reference to colorectal neoplasia.
The last session of the day which most of the younger participants were looking forward
to, was the IACR Oral Award Presentation chaired by Dr. Asok Antony [RLRVAMC,
USA] and Dr. Nishigandha Naik [Nicholas Piramal Research Centre, India]. There were
twelve contestants below the age of 30 years from institutions across the country, for the
Sitaram Joglekar award and the Mangala Bamne award, who made excellent
presentations on subject areas ranging from epigenetics, apoptosis, and
immunoproteomics to chemoprevention in Cancer research. The enthusiasm and the
competence were very much appreciated by the accomplished audience.
On the third and final day of the conference there were three scientific sessions. The day
began with the session on Clinical Cancer Research chaired by Dr. Kirti M. Patel
[GCRI, India] and Dr. Yogeshwar Shukla [ITRC, India]. The Keynote lecture by Dr.
Shilin Shukla
[GCRI, India] on the, "GCRI Research Wing Perspectives", introduced the
various research activities carried out in the Institute, its strengths, and the focus of
activity in the immediate and near future. It was a good overview of the quantity and
quality of scientific pursuit by the various investigators at the GCRI, in the thrust areas of
cancer research.
Dr. Sharmila Bapat [NCCS, Pune] spoke on," Ovarian Cancer Stem Cell Biology". It
was a much ‘awaited' talk, as the present attraction and interest for most cancer
researchers is the area of cancer stem cells. She spoke of the ovarian stem cell model
system established, the different clones identified and the availability of this tool to study
cancer stem cells and identify disruption of the normal stem cell regulation during cancer.
Discussed the mitochondrial DNA profile of the clones and the clones isolated involved
in endothelial vasculature. With the endothelial lineage marker, V-cadherin, showed a re-
association of endothelial cells with the tumour cells, basically identifying a novel
mechanism of mediation of long-term angiogenesis employed by CSCs towards ensuring
tumour survival. Epigenetic regulation of self-renewal and differentiation in Cancer stem
cells and that bivalent histone marks regulate a transcriptional plasticity was also
discussed.
Dr. Rita Mulherkar [ACTREC, India] gave a talk entitled "Strategies and Vectors for
Cancer Gene Therapy: Preclinical Studies at ACTREC". She discussed the prodrug
activation strategy using Herpes simplex virus – thymidine kinase and ganclicovir, in a
xenograft nude mouse model, developed in her lab, for head and neck squamous cell
carcinoma [HNSCC] and the preclinical studies done to treat head and neck squamous cell carcinomas with this strategy, administered using viral vectors. The use of the combination gene therapy approach of HSV-tk and IL-2 to bring about enhanced tumour cell kill and the use of shRNA to silence genes like cyclin D1 and ATM with the ultimate aim of sensitizing HNSCC tumours to conventional therapy was also lucidly discussed. The proof of the pudding would be when these studies are translated into the clinic and benefit patients who are otherwise untreatable by conventional therapy.
The session on HPV and Neoplasia was chaired by Dr. Sudhir Krishna [NCBS, India].
Dr. Antony Asok [RLRVAMC, USA] began the session with his talk entitled
"Homocysteine –derivatized heterogeneous nuclear ribonucleoprotein –E1 profoundly
inhibits both HPV-16 Viral capsid proteins via multiple mechanisms" The talk covered
aspects of nutritional deficiencies of folate and vit B12 which have been implicated in
HPV infection and pathogenesis of cervical cancer, but as yet, little understood. There are
several reports in literature, which describe folate and vitamin deficiency as a risk factor
in HPV infection and cervical cancer, But this talk opened up another interesting aspect
of folate deficiency, and that is the inability of the infectious viral particle to form due to
accumulation of homocysteine and the concomitant inibition of the viral capsid proteins.
Dr. Sudhir Krishna [NCBS, India] spoke about Identifying and characterizing ‘Putative
Cancer' stem cells and their signaling properties. He reviewed the cancer stem cell
hypothesis, the sphere formation assay that has been classically used to identify stem like
cells in culture, and which was also used to identify cancer stem cells. Some of the points
that were reiterated were of the marker CD24+ being associated with breast cancer stem
cells, and its reduction after cancer chemotherapy, the heterogenous expression of CD133
in cell lines, and that ‘Notch signaling' could also be an important marker for human
cervical cancers.
Dr. Mausumi Bharadwaj [ICPO, India] presented preliminary data relating to the
genetic polymorphism of HLA in HPV mediated cervical cancer in Indian women. Her
study has revealed that SNPs at -308 G/A and -863 C/A loci of TNF α promoter as well
as + 252A/G locus of LTA along with DRB1*15/DQB1*03 region of HLA may play a role in cervical carcinogenesis.
The last session of the conference on, Signal Transduction and Cancer was chaired by
Dr. Asok Antony[RLRVAMC, USA] and Dr. Franz Bosch [University of Heidelberg,
Germany]. The session opened with the talk, "Semaphorin 5a, an axonal regulator, with
potential role in tumour angiogenesis, growth and metastasis" by Dr. Rakesh Singh
[UNMC, USA]. He presented findings which predicted that Semaphorin 5A is a
metastasis associated molecule in pancreatic cancer by performing sequence and
expression database analysis using peptides screened from in vivo phage display peptide
library and also developed a searchable mammalian cell adhesion molecule database for
the identification of Semaphorin 5A. Further, hypothesized that Semaphorin 5A is
involved in pancreatic tumour progression and metastasis. Their observations were that
metastatic pancreatic cancers express Semaphorin 5A.It was expressed on cell- cell
junctions and membrane. All pancreatic tumours express Sem5A irrespective of their
differentiation status. Over expression leads to an increased invasive potential. Also
observed that secreted [Panc1 cells] Semaphorin 5A enhances the endothelial cell
proliferation and survival of endothelial cells, has in-vivo angiogenic activity, a
functional role in epithelial –mesenchymal transition, and mesenchymal epithelial
transition as well, which occurs for establishment of tumours in distant organ
microenvironment. So with their studies on Semaphorin 5A, they have been able to
assign a bi-functional status of an enhancer and a repressor of tumour progression and
metastasis, and explore its potential as a marker as well as a therapeutic target for
pancreatic cancer.
Dr. Bharvin Patel [Eli Lilly,USA] spoke about "New drugs and Biomarkers in Clinical
Development". Presented examples of some drugs that have been developed to target key
molecules involved in tumour growth and survival. Described Enzastaurin, which has
been taken into a phase III trial by the company for the treatment of relapsed
glioblastoma multiforme [GBM]. Added that Enzastaurin has been shown to suppress
signaling through the PKC β and PI 3 kinase/AKT pathways. It has also been shown to
inhibit angiogenesis by the rat corneal micropocket assay and bring down the GSK3β
levels. Mentioned other drugs like Gemzar and Alimta, both antimetabolites that are used in combination with other drugs in treatment of various cancers. The other highlights of the talk were about an inhibitor developed to the TGF-β receptor, which is highly specific and does not bind to PDGF or bFGF receptor and also survivin.
Dr. Shubhada Chiplunkar [ACTREC, India] gave a talk entitled," Mechanisms of CD3
Down- Regulation in Patients with Oral Cancer". She discussed Immunoediting and how
the tumour brings about changes in the T cell signaling molecule. Spoke about their
observations that lymphocyte infiltration in oral cancers is good, but the cells don't seem
to be equipped to kill tumour cells and also the TILs undergo apoptosis. Stage III and IV
showed lower expression of zeta, internalization of zeta, lower protein levels and no Zap
70 degradation. Recycling of zeta is impaired, remains internalized in oral cancers. There
are no changes in biosynthesis of zeta in oral cancers and studies are in progress to
characterize the tumour-derived factor responsible for the degradation of CD3 chain
expression in oral cancer. Emphasized that a posttranslational defect is predominant in
the peripheral blood lymphocytes, while a transcriptional defect is responsible for the
decreased CD3 chain expression in the tumour compartment.
The last talk of the conference and the day was by Dr. Nishigandha Naik [Piramal Life
Sciences Ltd, India] on "Role of Formyl Peptide Receptors in Breast Cancer Cells" She
introduced Formyl peptide receptors and their functions in injury and infection and
emphasized that scientific literature shows that these receptors are present on non-
haematopoietic cells, which led to her work of exploring the possibility of its expression
on cells of epithelial origin, like breast cancer. Several cell lines were studied and the
findings showed that breast cancer cells express FPR and also that FPR may play a role in
regulation of cell growth and cell motility by stimulating multiple signaling pathways.
The Convention concluded with the ‘Valedictory Function' conducted by the Organizing
Secretary, Dr. Sunil Trivedi, with the gracious presence of the members from the
Organizing and the IACR Committee. The invited speakers and participants of the
conference were acknowledged for making the meeting a scientifically stimulating
experience. The office bearers as well as the volunteers were profusely thanked for their
efforts and enthusiasm. During the formalities, the younger participants seemed impatient
for the announcement of the IACR awards for the oral and the poster presentations,
which always evokes fulfillment or inspiration. The IACR, Sitaram Joglekar award for
one of the best oral presentations went to Miss. Triparna Sen [CNCI, Kolkata, India]
for her talk entitled," Effect of Green Tea Polyphenol-EGCG on the expression and
activity of MMP-2 in human breast cancer cell line MCF-7". The IACR Mangala
Bamane
award for one of the best oral presentations was bagged by Mr. Rohit
Upadhyaya
[SGPGIMS, Lucknow, India] for his presentation entitled, "Functional
Polymorphisms of Cyclooxygenase –2 gene and risk for esophageal cancer". The IACR
Rajnikant Baxi
award for one of the best poster presentations was given to Miss.
Toral Kobawala
[GCRI, India] for her poster entitled," Molecular alterations in oral
carcinogenesis: Significant risk Predictors in malignant transformation and tumour
progression". The IACR Rambhau Kulkarni award for one of the best poster
presentations went to Mr. Nallala Krupakar [ACTREC, India] for his poster entitled,"
Genetic predisposition to multiple primary neoplasms–High throughput analysis of
SNP's using SnaPshot." The Organizers of the Convention had announced prizes for the
non – awards section of the poster presentation and this prize was bagged by Mr. Ganesh
Joshi
[ACTREC, India] for his poster entitled, "HDAC inhibitor Valproic acid enhances
the Adenovirus mediated Transgene Expression"
The best essays, in the competition held by the IACR earlier last year, were of Miss.
Toral Kobawala
[GCRI, India] and Mr. Harshit Kumar Soni [NCL, Pune, India].
It was on this very encouraging and positive note that the Convention came to an end with participants hoping to come with and present interesting and excitng science next year.

Source: http://www.iacr.org.in/docs_pdfs/Report%20of%2027th%20Annual%20IACR%20Convention.pdf

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FOR IMMEDIATE RELEASE CONTACT: FDA APPROVES THE FIRST 3D PRINTED DRUG PRODUCT Aprecia Introduces its First Product Using the ZipDose® Formulation Platform for the Treatment of Epilepsy BLUE ASH, Ohio, August 3, 2015 – Aprecia Pharmaceuticals Company today announced that the U.S. Food and Drug Administration (FDA) has approved SPRITAM® levetiracetam for oral use as a prescription adjunctive therapy in the treatment of partial onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures in adults and children with epilepsy. 1 SPRITAM utilizes Aprecia's proprietary ZipDose® Technology platform, a groundbreaking advance that uses three-dimensional printing (3DP) to produce a porous formulation that rapidly disintegrates with a sip of liquidWhile 3DP has been used previously to manufacture medical devices, this approval marks the first time a drug product manufactured with this technology has been approved by the FDA. "By combining 3DP technology with a highly-prescribed epilepsy treatment,2 SPRITAM is designed to fill a need for patients who struggle with their current medication experience," said Don Wetherhold, Chief Executive Officer of Aprecia. "This is the first in a line of central nervous system products Aprecia plans to introduce as part of our commitment to transform the way patients experience taking medication." ZipDose Technology enables the delivery of a high drug load, up to 1,000 mg in a single dose.2 As a result, SPRITAM enhances the patient experience - administration of even the largest strengths of levetiracetam with just a sip of liquid. In addition, with SPRITAM there is no measuring required as each dose is individually packaged, making it easy to carry this treatment on the go. SPRITAM is expected to be available in the first quarter of 2016. "In my experience, patients and caregivers often have difficulty following a treatment regimen. Whether they are dealing with a swallowing disorder or the daily struggle of getting a child to take his or her medication, adherence can be a challenge," said Marvin H. Rorick III, M.D., neurologist at Riverhills Neuroscience in Cincinnati, Ohio. "Especially for children and seniors, having an option for patients to take their medication as prescribed is important to managing this disease." Nearly three million people in the United States have been diagnosed with active epilepsy, with an estimated 460,000 of those cases occurring in children. 3 Additionally, in a recent survey of people age 65 and older living in an independent living facility, 15 percent reported difficulty swallowing.4 Other chronic conditions can impair the ability to swallow, further exacerbating the problem.5 While there are many reasons, including swallowing difficulties, for which patients may not take their medication as prescribed, missed doses of medication can undermine

whatsupdoc.tv

El ejército que ¿Qué queda de las Fuerzas Armadas que rompieron la democracia en Chilehace 30 años? Seguramente, más la forma que el fondo. Por primera vez, la Escue-la Militar, el gran centro de formación de oficiales, ha abierto sus puertas. Asíson los nietos uniformados del ex dictador. Por Francesc Relea. Fotografía de Luis Poirot.