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Centre for Cancer Biomarkers CCBIO

CCBIO Junior Scientist Symposium

The CCBIO Junior Scientist Symposium represents an integrated part of the CCBIO Research School for Cancer Studies. This is a seminar series that aims to improve scientific interaction and networking among junior researchers.

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Collage of photos from teaching at the CCBIO Junior Scientist Symposia.
The CCBIO Junior Scientist Symposium is an arena where PhD candidates and postdocs gain experience with oral presentations and academic discussions, and also occasionally be inspired by CCBIO PIs.
Photo:
Anne S.Herdlevær/Ingvild Melien/CCBIO/Colourbox.

The participants are very satisfied with these seminars. We receive comments on the high level of the research and presentations, as well as the positive side of getting to know colleagues in other CCBIO research groups. The small-talk goes lively in the breaks, suggesting that new and fruitful research collaborations might get started here.

Researcher Erling Høivik and Postdoc Agnete Engelsen, coordinators of the junior seminars in 2017, are planning and chairing these meetings. 

Planned next dates for the Scientist Symposia:

June 15th 2017, August 31st 2017 and November 23rd 2017.

 

Read the Course description for CCBIO901.

Read also article Great interest in the CCBIO Junior Scientist Symposia

 

Below you can find the programs of the earlier symposia.

February 2017

February 23rd 2017

Auditorium B-­‐301, Haukeland University Hospital
10.00-­14.00

Symposium Chairs: Agnete Engelsen and Erling Høivik

SCIENTIFIC PROGRAM

10.00-10.50: 'Inspirational lecture' by Professor Ola Myklebost (K2):NoSarC – Norwegian Sarcoma Consortium (www.NoSarC.no), - Personalised treatment for orphan cancers

10.50-11.00: Coffee break

11.00-11.45: Caroline Benedicte Nitter Engen (K2): Personalised medicine and the evolution of new health entities and identities

11.45-12.45: Lunch (lunch included, please specify upon registration)

12.45-13.15: Hege Avsnes Dale/ Endy Spriet (Molecular Imaging Center (MIC)): Introduction to super-resolution imaging

13.15-13.20: Coffee break

13.40-14.00: Hanna Dillekås (K2): Recurrence of breast cancer in relation to delayed reconstruction

13.20-13.40: Sigmund Ytre-Hauge (K2): MRI texture analysis in endometrial cancer

 

 

December 2016

December 8th 2016 10.00-14.00 

Auditorium, Hudbygget, Haukeland University Hospital.

Symposium Chairs: Elisabeth Wik and Erling Høivik

SCIENTIFIC PROGRAM 

10.00-10.45: Inspirational lecture: Professor Arild Raaheim (Department of Education, UIB): A supervisor's view on supervision. Challenges and possibilities

10.45-11.00: Coffee and gingerbreads

11.00-11.20: Karen Mauland (K1): High proportion of visceral fat is linked to poor endometrial cancer outcome

11.20-11.40: Gry Sandvik Haaland (IBM): Warfarin use and cancer incidence

11.40-12.00: Trung Ha (K2): Preclinical Activity and Molecular Mechanisms of Resazurin in Acute Myeloid Leukemia

12.00-12.40: Lunch (lunch included, please specify upon registration)

12.40-13.00: Hanna Dillekås (K1): Recurrence of breast cancer in relation to delayed reconstruction

13.00-14.00: Inspirational lecture: Professor Curtis Harris (Center for Cancer Research, National Cancer Institute, NIH): Integration of "OMIC" Biomarkers: A Precision Medicine Strategy for Lung Cancer

You can read an article about the December Junior Scientist Symposium here.

 

August 2016

August 25th 2016, 10.00-14.00. 

Auditorium B301, Haukeland University Hospital, Sentralblokken (main building), Bergen. 

Symposium Chairs: Agnete Engelsen and Elisabeth Wik

 

SCIENTIFIC PROGRAM

10.00-10.50:   'Inspirational lecture' by Professor Daniela Elena Costea (K1)

10.50-11.00:   Coffee break

11.00-11.20:   Øystein Eikrem (K1): New methods clear dust off old biopsies - RNA sequencing of FFPE tissues

11.20-11.40:   Kjersti Davidsen (IBM): Introduction to cancer immunotherapy

11.40-12.00:   Kjersti Davidsen (IBM): Enhancing the effect of immune checkpoint inhibition by targeting Axl

12.00-13.00:   Lunch (lunch included, please specify upon registration)

13.00-13.20:   Maria Kolnes Lie (IBM): Inhibition of Axl in erlotinib-resistant NSCLC cells abrogates autophagic flux and induces immunogenic cell death

13.20-14.00:   Kjell Petersen (Department of Informatics): Integrated dataanalysis of proteomics and transcriptomic data from brain cancer model

 

April 2016

April 28th 2016, 10.00-14.00. 

Auditorium B301, Haukeland University Hospital, Sentralblokken (main building), Bergen. 

Symposium Chairs: Agnete Engelsen and Elisabeth Wik

 

PROGRAM:

10.00-10.05    Welcome and introduction to the PhD course CCBIO 901

10.05-10.25:   Katharina Bischof: Prognostic and predictive markers in high grade  serous ovarian carcinoma

10.25-10.45:   Deusdedit Tusubira: Repression of mitochondrial respiration is an important step in epithelial to mesenchymal transition (EMT)

10.45-11.00:   Coffee break

11.00-12.00:   Nils Halberg: Inspirational lecture

12.00-13.00:   Lunch (lunch included, please specify upon registration)

                        Proteomics session:

13.00-13.20:   Frode Selheim: PROBE: A core facility for mass spectrometry based proteomics

13.20-14.00:   Even Birkeland and his master student Silje Kjølle: Secreted proteins in breast cancer, a proteomics approach

 

February 2016

February 25th 2016, 10.00-14.00
Auditorium 2, BBB
10.00-14.00 

Symposium Chairs: Agnete Engelsen and Elisabeth Wik

If you want to attend, we kindly ask you to register your attendance and lunch preferences through this link within February 24th.

PROGRAM:

10.00-10.20:   Maria Ramnefjell: Vascular invasion and vascular proliferation are adverse prognostic factors in non-small cell lung carcinoma

10.20-10.40:   Saroj Rajthala: Micro-RNA profiling of oral cancer stroma

10.40-11.00:   Konstantina Dimitrakopoulou: Gene expression deconvolution in complex tissue samples

11.00-11.15:   Coffee break

11.15-12.00:   Cecilie Gudveig Gjerde, the winner of 'Forsknings Grand Prix' 2015: Research communication - business or pleasure?

12.00-13.00:   Lunch (lunch included, please specify upon registration)

13.00-13.20:   Mahdi Hassan-Olive: Thioridazine sensitizes glioblastoma cells to temozolomide by impairing autophagy

13.20-13.40:   Henriette Ertsås Christie: Microenvironment-contextual cell signaling is attenuated with age

13.40-14.00:   Jessica Furriol: IL8 gene polymorphisms in combination with clinical factors predict disease free survival in breast cancer patients

You are all very welcome! Please feel free to circulate this information if you know of other researchers/staff that you think would find this symposium interesting. 

November 2015

November 26th 2015
Auditorium 4, BBB

Symposium Chairs: Agnete Engelsen and Elisabeth Wik

PROGRAM

  • 10.00-11.00 Professor Roger Strand "Cancer: illness, disease and sickness". Inspirational lecture with plenary discussion. Abstract available.
     
  • 11.00-11.10 Coffee break
     
  • 11.10-11.30: Pugazendhi Murugan Erusappan: The role of the cytoplasmic tail of integrin alpha 11
     
  • 11.30-11.50 Martin Pilskog: Analysing response of sunitinib treatment in metastatic renal cell carcinoma.
     
  • 11.50-12.10 Anna Berg: Tissue and imaging biomarkers for hypoxia predicts poor outcome in endometrial cancer
     
  • 12.10-13.00 Lunch (included, please specify upon registration)
     
  • 13.00-13.20 Gry Haaland: Register based cancer research -challenges and opportunities
     
  • 13.20-13.40 Stein-Erik Gullaksen: Mass Cytometry in Bergen
     
  • 13.40-14.00 Fanny Pelissier: High dimensional analysis of age-related phenotypic diversity in human mammary epithelial cells

September 2015

September 17th 2015
Auditorium 4, BBB

Symposium Chairs: Agnete Engelsen & Elisabeth Wik

PROGRAM – CCBIO Junior Scientist Symposium

  • 10.00-10.20 Anne Blanchard: Big pharma, medicalisation and the good life
  • 10.20-11.05 Bjørn Tore Gjertsen: How to succeed in cancer research (Or how do you define yourself into success…)
  • 11.05-11.20 Break
  • 11.20-11.40 Henriette Cristie Ertsaas: Microsphere cytometry to study microenvironment contextual cell signaling
  • 11.40-12.00 Kristi Krüger: Nestin expression in breast cancer – a marker for angiogenesis and the basal-like phenotype
  • 12.00-13.00 Lunch
  • 13.00-13.20 Synnøve Yndestad: The PTEN pseudogene, friend or foe? A Long non Coding RNA that influences breast cancer through ceRNA network and microRNA interactions.
  • 13.20-13.40 Yaping Hua: Development of a small molecule for treatment of castration recurrent prostate cancer via androgen receptor and IL6/STAT3 pathway.
  • 13.40-14.00 Tiina Jokela: Dissection of mammary stem cell and cancer stem cell niche.

Read article about the September Junior Scientist Symposium.

 

April 2015

April 30th 2015

Auditorium 4, BBB

Symposium Chairs: Camilla Krakstad & Elisabeth Wik


PROGRAM – CCBIO Junior Scientist Symposium April 30th 2015

10.15-11.00 Gyri Wester: The moral significance of the social inequalities in health: Some policy implications

11.00-11.15 Break

11.15-12.00 Liv Cecilie Vestrheim: The immune system's response; a common denominator in preeclampsia and cardiovascular disease

12.00-12.40 Lunch

12.40-13.00 Calum Leitch: Repositioning Hydroxyurea and Valproic Acid as combination therapy in Acute Myeloid Leukaemia

13.00-13.20 Caroline Reed: TBA

13.30-13.40 Break

13.40-14.00 Dipak Sapkota: S100A16 Promotes Differentiation and Functions as a Tumor Suppressor in Oral Squamous Cell Carcinoma

February 2015

February 12th 2015
Auditorium 2, BBB

Symposium Chairs: Camilla Krakstad & Elisabeth Wik


PROGRAM – CCBIO Junior Scientist Symposium

  • 10.00-10.40 Marion Solheim: Scientists and the media
  • 10.40-11.00 Break
  • 11.00-11.20 Karen Mauland: Aneuploidy predicts aggressiveness and poor prognosis in endometrial cancer, and is reflected in a 9-gene signature
  • 11.20-11.40 Sura Aziz: Assessment of the proliferation markers in lymph node metastasis in breast cancer and their impact on survival
  • 11.40-12.40 Lunch
  • 12.40-13.20 Cecilie Brekke Rygh: Preclinical PET/CT at UoB
  • 13.20-13.30 Break
  • 13.30-13.50 Lavina Ahmed: Axl as a biomarker for cancer EMT
  • 13.50-14.00 Concluding remarks

October 2014

October 30th 2014

PROGRAM – 3rd CCBIO Junior Scientist Symposium

Symposium Chairs: Camilla Krakstad & Elisabeth Wik

  • 10.00-10.45 Lars Herfindal: Therapeutic nanocarriers for improved cancer chemotherapy
  • 10.45-11.00 Break
  • 11.00-11.20 Elisabet Ognedal Berge: WBC BRCA1 methylation predicts risk of OC
  • 11.20-11.40 Rakel Brendsdal Forthun: Phosphoprotein expression in AML patients reflects patient stratification
  • 11.40-12.30 Lunch
  • 12.30-13.00 Anne Blanchard: "Why your new cancer biomarker may never work”: Cancer research between hope and despair
  • 13.00-13.20 Himalaya Parajuli: Expression of integrin á-11 by carcinoma associated fibroblasts modulates oral squamous cell carcinoma behavior
  • 13.20-13.40 Break
  • 13.40-14.00 Sebastien Bougnaud: Tumor/stroma dynamics during tumor development and treatment

August 2014

PROGRAM – 2nd CCBIO Junior Scientist Symposium August 28th 2014

Symposium Chairs: Camilla Krakstad & Elisabeth Wik

 

  • 10.00-10.45 Gro Vatne Røsland: Trial lecture: Role of quiescent tumour cells in therapy resistance and cellular differentiation
     
  • 10.45-11.00 Break
     
  • 11.00-11.20 Erling Høivik: Exome sequencing of matched primary and metastatic tissues in endometrial cancer
     
  • 11.20-11.30 Info CCBIO-901
     
  • 11.30-12.30 Lunch
     
  • 12.30-12.50 Cornelia Schuster: Predictive markers for treatment with bevacizumab monotherapy in metastatic melanoma
     
  • 12.50-13.10 Maria Omsland: Cell-to-Cell Communication in Acute Myeloid Leukemia by Tunneling Nanotubes
     
  • 13.10-13.20 Break
     
  • 13.20-13.40 Jan Roger Olsen: Signal transduction and transcription factor activation in prostate cancer
     
  • 13.40-14.00 Even Birkeland: The rationale behind a proteomics approach to discover breast cancer biomarkers

 

Abstracts

 

The Role of Quiescent Tumour Cells in Therapy Resistance
Gro Vatne Røsland

Abstract
Therapy resistance represents the main challenge to successful cancer therapy, and it has recently been proposed that quiescent cancer cells may contribute to tumor relapse, metastasis and therapy resistance.

Cellular quiescence is defined as a dynamic, reversible state in which the cell is not actively dividing. The state of quiescence has predominantly been associated with adult stem cells. During tissue homeostasis, hematopoietic stem cells are known to transpose to and from the state of quiescence in order to maintain their stem cell properties. Moreover, quiescence is a crucial hallmark of stem cells, which allow them to preserve stemness and avoid differentiation. Specific niches are postulated to be essential in regulating entrance into the state of
quiescence, both in regards to the oxygen levels, as well as other microenvironmental factors. The development of cancer has been compared to the development of a neo‐organ, and the composition of intra‐tumoural microenvironmental niches may thus be paralleled with stem cell niches in healthy tissue.

Subpopulations of tumour cells exhibiting stem cell properties have been identified and shown to be involved in both initiation, as well as development of multiple kinds of cancers. Moreover, it has been shown that these cells possess an elevated clonogenic potential and therapy resistance, compared to more differentiated cancer cells. In evolving tumors, cellular entrance into the state of quiescence may protect the cancer cells from various cancer therapies.

As quiescent tumor cells challenges current treatment paradigms, the development of therapeutic strategies targeting quiescent tumour cells hold promise for overcoming major hurdles to successful cancer therapy.


Exome sequencing of matched primary and metastatic tissues in endometrial cancer
Erling Høivik

Abstract
Although the majority of endometrial carcinomas are diagnosed at an early stage, 15‐20% of these patients develop metastatic disease. Patients with recurrent endometrial disease have reduced survival, lack effective targeted therapies and the molecular genetic alterations  causing progression to metastasis remain poorly elucidated. In line with the need to characterize advanced cancer progression, the early events leading to cancer progression also needs to be enlightened, and hyperplasia of the endometrium is considered a precursor lesion of endometrial cancer. We have performed exome sequencing of a unique panel of endometrial cancers including hyperplasias, primary tumors and matching metastases to characterize the patterns of genetic alterations that occur towards cancer progression. Initial results will be discussed up against the large study performed by The Cancer Genome Atlas (TCGA) Research Network consortium (Nature 2013).


Predictive markers for treatment with bevacizumab monotherapy in metastatic melanoma
Cornelia Schuster, Lars A. Akslen, Oddbjørn Straume

Abstract
Angiogenesis is a hallmark of cancer and essential for tumor growth and metastases. It is known that melanomas often are highly vascularized. The main objective of this study was to identify predictive markers for anti‐angiogenic treatment in patients with metastatic melanoma treated with bevacizumab monotherapy in a phase II clinical trial. As previously published, this treatment is well tolerated and showed disease control (CR, PR and SD for at least 6 months) in 31% of the patients.
Primary tumors, metastases and blood samples were investigated by immunohistochemistry and ELISA. Vascular endothelial growth factor (VEGF‐A), the splice variant VEGF165b, basic fibroblast growth factor (bFGF) and heat shock protein 27 (HSP27) were assessed.
100% of the patients with high HSP27 expression in metastases had either complete remission or partial response. Conversely, none of those with low HSP27 staining responded to treatment with bevacizumab monotherapy. All patients with high expression in primary tumors showed a non‐significant trend to better treatment response. In contrast, neither VEGF‐A, VEGF165b nor bFGF staining in primary tumors or metastases predicted response. Measurements of HSP27 and bFGF in serum and VEGF165 in plasma did not show any correlation to treatment response.

In conclusion, high expression of HSP27 in metastases is significantly associated with response to treatment with bevacizumab monotherapy in patients with metastatic melanoma.


Cell‐to‐cell communication in acute myeloid leukemia by tunneling nanotubes
Maria Omsland

Abstract
Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer originating in the bone marrow. Conventional therapy is not well tolerated by elderly patients and the survival rate is limited. An improved understanding of cellular communication in AML could provide new information with respect to disease‐linked mechanisms, progression, treatment and resistance. The tunneling nanotube (TNT) is a novel type of cell‐to‐cell communicator, 50‐200 nm in diameter, F‐actin containing structure connecting two or more cells. TNTs have been observed in a variety of cells including macrophages, B and T‐cells, different cancer cells and osteoclasts. It has been shown to transport various cell components including mitochondria, in addition to spread pathogens like viruses and bacteria. TNT has also been suggested to have a role in transfer of multi‐drug resistance genes. The exact molecular mechanisms behind TNT formation are still unclear, but the TNFαIP2 protein, found to be important in hematopoiesis, is one of the suggested molecules needed for TNT formation.

We have demonstrated the existence of TNTs in both AML cell lines and primary AML cells. We observed a variance in TNT numbers between the different cell types and greatest deviation was observed in the patient samples. The chemotherapeutics daunorubicin and idarubicin demonstrated a tendency of TNT increase while AraC quenched TNT formation. The functional impact of TNT in bone marrow and the potential role in AML therapy together with the role TNT play in drug transfer will be further investigated.


Signal transduction and transcription factor activation in prostate cancer
Jan Roger Olsen, Anne Margrete Oyan, Waqas Azeem, Margrete R. Hellem, Kristo Marviyn, Xisong Ke, Karl‐Henning Kalland

Abstract
Androgen receptor (AR) is a hormone receptor that upon ligand binding dimerizes and translocates from the cytoplasm to the nucleus where it functions as a transcription factor. Prostate cancer is dependent on androgen signalling through the AR. Clinically this is illustrated by the effect of castration on disseminated disease, and the effect of new anti‐androgens and inhibitors of local steroid synthesis as the cancer becomes castration‐resistant. AR‐activation in castration‐resistant disease can occur through AR‐amplification, AR alternative splicing (which renders the AR androgen‐independent), local steroid synthesis and receptor promiscuity. Even if prostate cancers show a strong selection pressure for AR signalling, tumours inadvertently relapse following blockade of AR‐signalling and the effect of AR‐signalling blockade on  long‐term survival is debated. AR‐signalling blockade also leads to stronger activation of alternative signalling pathways, among those the IL6‐STAT3 axis which we previously have shown to be fundamental in our cell model of prostate carcinogenesis, provoking the question if anti‐androgen treatment digs its own grave.

Additionally, in vitro studies have shown that AR expression leads to irreversible growth inhibition in primary benign epithelial prostate cells. What then is the context that promotes the pro‐carcinogenic effect of AR seen in vivo?


The rationale behind a proteomics approach to discover breastcancer biomarkers
Even Birkeland

Abstract
During the last fifteen years the advances in molecular genomics and transcriptomics has provided valuable insights in the biology of breast cancer. However, this has not had the impact on breast cancer treatment that was anticipated. Few studies have focused on the breast cancer proteome (all expressed proteins).
While it is estimated that the human genome comprises between 20,000 and 25,000 genes, the number of proteins in the human proteome is estimated at over 1 million.
Hence, a proteomics approach may identify novel protein biomarkers related to specific breast carcinomas with distinct underlying gene aberrations to further refine the existing molecular classification. Moreover, proteomics might reveal biological insights and identify protein biomarkers defining differences in therapy resistance, metastatic spread within a specific subtype, and patient prognosis.

 

June 2014

PROGRAM – 1st CCBIO Junior Scientist Symposium June 11th


Symposium Chairs: Camilla Krakstad & Elisabeth Wik

  • 10.00-10.10 Lars A. Akslen Welcome and introduction
  • 10.10-10.30 Tarig Al-Hadi Osman: Multiple immunostaining identifies separate cancer stem cell subpopulations in oral squamous cell carcinoma
  • 10.30-10-50 Emilia Hugdahl: BRAF-V600E expression in primary nodular melanoma: significance for survival and association with pathological features
  • 10.50-11.00 Break
  • 11.00-11.20 Ingrid Moen: Anti-metastatic action of inhibiting FAK and VEGFR-2 together in pancreatic neuroendocrine tumors
  • 11.20-11.40 Agnete Engelsen: Axl regulates stemness in adult lung alveolar epithelial homeostasis and NSCLC drug resistance
  • 11.40-12.30 Lunch
  • 12.30-12.50 Anne Blanchard: The ELSA team of CCBIO: some ethical questions around cancer biomarkers
  • 12.50-13.10 Mari Halle: Molecular profiling in fresh tissue with high tumour cell content promotes enrichment for aggressive uterine adenocarcinomas
  • 13.10-13.20 Break
  • 13.20-13.40 Ning Lu: Integrin α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids
  • 13.40-14.00 Rakel Brendsdal Forthun: Phosphoprotein expression in AML patients reflects patient stratification

Abstracts

 

Identification of Phenotypically Distinct Cancer Stem Cell Subpopulations in Oral Squamous Cell Carcinoma
Tarig A. Osman, Oddveig Rikardsen, Muy-Teck Teh, Dipak Sapkota, Xiao Liang, Evelyn Neppelberg, Adrian Biddle, Ian Mackenzie, Lars Uhlin-Hansen, Anne Ch. Johannessen and Daniela Elena Costea

Abstract
Background: Several markers have been shown to define subpopulations enriched for cancer stem cells (CSCs) and correlate with poor clinical outcome in oral squamous cell carcinoma (OSCC).
Purpose: To investigate the pattern of expression and correlation with clinical parameters of two CSC markers, namely p75NTR and ALDH1A1, in both patient samples and cell lines.
Experimental design: Archival formalin-fixed paraffin embedded samples from normal human oral mucosa (NHOM, n=31), patients with oral dysplasia (OD, n=10) or OSCC (n=177) were subjected to multiple IHC and some to qRT-PCR for expression of CSC and proliferationrelated
markers, BMI1 and Ki67. Correlations between CSC marker expression and clinical parameters were investigated. Primary cells and cell lines derived from NHOM, OD or OSCC were FACS- analyzed for the same markers.
Results: A higher frequency of cells positive for CSC markers was detected in OD and OSCC compared to NHOM. Co-localization of the two markers was a rare finding in OSCC as compared to NHOM or OD, and was more heterogeneous in OSCC cell lines than in OD and NHOM cells. Cells positive for p75NTR were more frequent in small size tumors, poorly to moderately differentiated tumors, and correlated with poor survival of patients otherwise (clinically) deemed as of better prognosis. Higher frequency of ALDH1A1+ cells was found to be associated with lymph node metastasis. Both p75NTR+ cells and ALDH1A1+ cells could emerge de novo from the respective negative sub-population after FACS sorting and in vitro growth, but with different kinetics.
Conclusion: Here we show that several stem cell sub-populations with distinct phenotypes co-exist in a tumor, each having impact on different clinical parameters. The cell  subpopulations identified by the use of different CSC markers were found to be dynamic
populations, able to switch between phenotypes. In addition, our data suggest also that the stem cell heterogeneity is acquired and evolve parallel with carcinoma progression.

Molecular profiling in fresh tissue with high tumor cell content promotes enrichment for aggressive uterine adenocarcinomas.
Mari Kyllesø Halle, Henrica Maria Johanna Werner, Camilla Krakstad, Hilde Engerud, Even Birkeland, Elisabeth Wik, Jone Trovik, Bjørn Bertelsen and Helga B. Salvesen.

Abstract
Many emerging tools for comprehensive molecular profiling of malignant lesions demand fresh frozen tissue with a high tumor purity. Often a tumor epithelial content of at least 80 % is recommended. This approach may lead to a systematic bias, and therefore we explore if this selection criterion lead to any systemic bias for the patient inclusion in uterine cancers. Clinicopathologic data for a population-based cohort of 553 patients with endometrial cancer and 328 patients with cervical cancer have been studied. Freshly frozen tumor specimens were collected from 424 patients and evaluated by haematoxylin stained frozen sections for tumor purity.
In the endometrial cancer series, high tumor cell purity (≥80%) was significantly associated with high patient age, postmenopausal status, high grade and non-endometrioid histology compared to patients with <80% tumor purity. Patients with ≥80% tumor purity had significantly lower disease specific 5-year survival rate of 76% compared to 86% for patients with tumors with <80% purity (p=0.02). In the cervical cancer series, high tumor purity was significantly more often found in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC)  P=0.03). For the subgroup of AC (n=40) there was a significant association between high tumor purity in the fresh frozen samples and later occurrence of recurrent disease (P=0.04). In SCC, no significant associations between tumor purity and disease stage, grade or outcome were found. Apparently in line with this, grade was found to influence prognosis in AC, but not in SCC.
Our findings suggest that selection of samples based on high tumor purity in fresh frozen tissue may introduce a selection bias towards aggressive disease in uterine adenocarcinomas. Thus, the prevalence of potential molecular biomarkers identified in AC in particular, should be validated in a population-based setting to further explore clinical relevance. Also, molecular biomarkers only prevalent in subgroups with low tumor purity may go undetected in sample collections enriched for high tumor purity.

Anti-metastatic action of inhibiting FAK and VEGFR-2 together in pancreatic neuroendocrine tumors
Ingrid Moen, Matthew Gebre, Vanesa Alonso-Camino, Debbie Chen, David Epstein and Donald M. McDonald.

Abstract
Focal adhesion kinase (FAK) is a cytosolic non-receptor tyrosine kinase involved in tumor invasion and metastasis. The present study sought to determine whether metastasis could be reduced by inhibition of FAK alone or together with vascular endothelial growth factor receptor-2 (VEGFR-2). OXA-11, a small-molecule amino pyrimidine inhibitor of FAK, was studied in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors where liver metastases are frequent at older ages. As invasion and metastasis have been reported to increase in this model after inhibition of VEGF signaling, we asked whether this effect could be overcome by administering OXA-11 together with an inhibitor of VEGFR-2 (DC101). After confirming that OXA-11 reduced FAK phosphorylation at Y397 and Y861 in tumors and liver at the therapeutic dose, we examined effects on primary tumors and liver metastases. Treatment of mice from age 14 to 17 weeks with OXA-11 alone reduced tumor vascularity and invasion but had only modest effects on metastasis. Administration of OXA-11 together with DC101 not only reduced tumor size, vascularity, and invasion, but also decreased the incidence, abundance, and size of liver metastases. Liver metastases were found in 100% of mice in the vehicle group, 84% in the OXA-11 group, and 79% in the DC101 group, but were found in only 48% of mice treated with OXA-11 plus DC101, and those present were smaller and less numerous. Together, the findings indicate that concurrent inhibition of FAK and VEGF signaling had beneficial effects on tumors and on the occurrence of liver metastases in RIP-Tag2 mice.

Axl regulates stemness in adult lung alveolar epithelial homeostasis and NSCLC drug resistance
Agnete Svendsen Tenfjord Engelsen

Abstract
Lung cancer is the leading cause of cancer death worldwide. Five-year lung cancer survival is only 15 per cent. Non-small cell lung cancer (NSCLC) comprise 85% of lung cancer cases, and unfortunately available systemic therapies fail to cure most lung cancer patients. Recently,
up-regulation and activation of the receptor tyrosine kinase (RTK) Axl has been identified as a clinically significant feature of acquired resistance to EGFR inhibitors in NSCLC, and Axl has been identified as a promising therapeutic target for overcoming drug resistance in NSCLC.

Axl belongs to the TAM family of RTKs. Unlike many other RTKs, the TAM receptors are found to be more prominently expressed postnatally extending into adulthood, but not widely or highly expressed during development. We hypothesize that Axl expression and activation is important for conferring plasticity in the alveolar population of adult progenitor cells.

While pathways regulating embryonic lung development have been well studied, the signaling pathways regulating cell proliferation, self-renewal or differentiation in the adult lung are still largely unexplored. Epithelial homeostasis in the adult lung alveoli is regulated by long-lived alveolar type 2 epithelial cells (AT2). These plastic AT2 cells are postulated to serve as multipotent progenitors in homeostasis of the alveolar lung epithelium.

We have shown that Axl expressing lung progenitor cells isolated from Axl-LacZ heterozygous mice by FDG fluorescence activated cell sorting are clonogenic in Epitehelial colony forming unit (Epi-CFU) assays. And furthermore that the Axl expressing cells are bipotent progenitors with the ability to differentiate into alvoeolar type 1 (AT1) and type 2 cells in heterotypic 3D organoid cultures in vitro.

Collectively, our results establish an important role for the Axl receptor in mediating stemness underlying lung homeostasis, as well as drug resistance in non-small cell lung cancer.


Early progress from the ELSA team of CCBIO: some ethical and social questions around cancer biomarkers
Anne Blanchard

Abstract
Within CCBIO, a research team has been mandated to explore the Ethical, Legal and Social Aspects (ELSA) of cancer biomarkers. This ELSA team is at the moment composed of two main investigators: Prof. Roger Strand, employed at 25%, and Anne Blanchard, who is a full-time post-doc. Both of them work at the Centre for the Study of the Sciences and the Humanities (or Senter for Vitenskapsteori, SVT) at the UiB; within the fields of philosophy of science and science and technology studies (STS), and are interested on issues of decision-making and governance at the science-society-policy interface. Anne started her post-doc in February 2014. The research is still in its early stages; therefore no results will be presented in the talk. Rather, Anne will present some key ELSA questions on cancer biomarkers, which have arisen from a literature review and informal discussions with CCBIO members. These broad questions will steer the ELSA efforts over the coming years, and include:
(i) What are the technical and scientific challenges related to cancer biomarker
discovery and development?
(ii) What is the role of science in broader cancer research?
(iii) What are the economic and institutional challenges facing cancer biomarkers?
(iv) What does it mean to be a just and caring society?

In the talk, Anne will expand a little bit on each of these questions. She will also map how these questions will be addressed (e.g., empirical data, methods), and what the next steps are for the ELSA team.


BRAF-V600E mutation in primary nodular melanoma: significance for survival and correlation with microscopic features
Hugdahl E, Ladstein R, Akslen LA

Abstract
Background. Nearly 50% of primary and metastatic melanomas harbor BRAF mutations, and the BRAF-V600E mutation accounts for approximately 70-80%. Recently, immunohistochemical detection of BRAF-V600E mutated protein in melanoma is reported to have both high sensitivity and specificity. Certain clinico-pathologic features are shown to be associated with BRAF mutation in primary melanoma, including younger age and superficial subtype. Presence of BRAF mutation in primary melanoma has not shown association with reduced survival, but the prognostic impact of BRAF-V600E protein expression has not yet been analyzed. This study sought to determine whether BRAF-V600E protein expression in nodular melanomas is associated with clinico-pathologic features and survival.
Materials and Methods. In a patient-series of 248 nodular cutaneous melanoma, BRAFV600E expression was assessed by immunohistochemistry using tissue microarray (TMA) sections of paraffin-embedded archival tissue.
Results. The staining was cytoplasmatic and generally homogenous. Difference in staining intensity between tumor areas was rarely observed, and mainly related to the presence of necrosis and fixation artifacts. Nuclear staining in tumor cells and cytoplasmatic staining of
epithelial cells was observed in a few cases.
BRAF-V600E was expressed in 191 (77%) of the 248 melanomas, and was significantly associated with increased tumor thickness, presence of tumor ulceration and high mitotic count. There was no association between BRAF-V600E expression and tumor necrosis, the mitotic marker PHH3, age, sex or tumor anatomic site. Cases with positive BRAF-V600E expression showed significantly reduced survival. Importantly, in multivariate analysis, BRAFV600E was an independent prognostic factor when compared with the histopathologic variables included in the pT system from 2010: tumor thickness, ulceration and mitotic count.
Conclusion. BRAF-V600E expression was associated with aggressive histopathological features and reduced survival in this cutaneous nodular melanoma series, and was an independent prognostic factor.


Fibroblast a11b1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids
Ning Lu, Tine V. Karlsen, Rolf K. Reed, Marion Kusche-Gullberg, Donald Gullberg

Abstract
We have previously shown that fibroblast expression of a11b1 integrin stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand the molecular mechanisms whereby a collagen receptor on fibroblast can regulate tumor growth we have used a 3D  heterospheroid system composed of A549 tumor cells and fibroblasts without (a11+/+) or with a deletion (a11-/-) in integrin a11 gene. Our data show that a11-/-/A549 spheroids are larger than a11+/+/A549 spheroids, and that A549 cell number, cell migration and cell invasion in a collagen I gel are decreased in a11-/-/A549 spheroids. Gene expression profiling of differentially expressed genes in fibroblast/A549 spheroids identified CXCL5 as one molecule down regulated in A549 cells in the absence of a11 on the fibroblasts. Blocking CXCL5 function with the CXCR2 inhibitor SB225002 reduced cell proliferation and cell migration of A549 cells within spheroids, demonstrating that the fibroblast integrin a11b1 in a 3D heterospheroid context affects carcinoma cell growth and invasion by stimulating autocrine secretion of CXCL5. We furthermore suggest that fibroblast a11b1 in fibroblast/A549 spheroids regulates interstitial fluid pressure by compacting the collagen matrix, in turn implying a role for stromal collagen receptors in regulating tensional hemostasis in tumors.
In summary, blocking stromal a11b1 integrin function might thus be a stroma-targeted therapeutic strategy to increase the efficacy of chemotherapy.


Phosphoprotein expression in AML patients reflects patient stratification
Rakel Brendsdal Forthun

Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease primarily occurring in the elderly population, with a median age of 67 years. For the patient group older than 65 years of age, the 5-year relative survival is only 5%. The disease is characterized by a block in differentiation of the myeloid hematopoietic cells and a clonal expansion of these undifferentiated cells. There are several parameters that can be used to stratify patients, with cytogenetic status having the highest prognostic impact. Although the patients are highly heterogeneous based on which myeloid cells are clonally expanded, cytogenetic aberrations and mutations acquired, treatment options for AML patients are highly similar and mostly based on a combination therapy of cytarabine and an antracycline.

In this study we investigated whether phosphoprotein expression could reflect current stratification strategies, including response to therapy and cytogenetic status, as well as mutational status of the highly prognosis-influencing receptor tyrosine kinase FLT3. By 2D difference gel electrophoresis (DIGE) and principal component analysis (PCA) we analyzed the phosphoproteome of leukemic cells harvested from 62 AML patients, and performed supervised clustering. Here we clearly defined patients according to the given classification parameters. Further, we found several proteins that might serve as biomarkers for patients who will respond to traditional chemotherapy, and proteins that are associated with increased risk of relapse and worsened prognosis. Our results are currently being validated by the novel multiple reactions monitoring (MRM) method, permitting quantitative analysis of target peptides by mass spectrometry (MS). The use of this method will permit a thorough analysis of potential biomarkers using scarce sample material, and potentiate the analysis of a future larger sample set.