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Browsing Over 1843 Presentations
34P - Molecular markers of response to different chemotherapeutic agents in RAS / BRAF mutated colon cancer cell lines
- Kevin Doello (Granada, Spain)
Abstract
Background
RAS mutated colon cancer has a worse prognosis than wild type (wt) with a median of about 20 months of OS and the BRAF mutated with an OS of about 10 months. In addition, we frequently find patients with therapeutic exhaustion. The objective of the present study is the definition of molecular markers of response to traditional chemotherapeutic agents and new drugs studied in RAS / BRAF mutated colon cancer.
Methods
The following colon cancer cell lines were used: HCT15, T84, HT29 and SW480 (molecular characteristics are summarized in the table). These cell lines were assigned to 5-fluorouracil, oxaliplatin, irinotecan, gemcitabine, pemetrexed, trabectidine and eribulin at different doses for 72 hours in order to obtain the inhibitory concentration 50 values (IC50). Likewise, RT-PCR studies were carried out in order to determine the expression of P-glycoprotein.
Results
The results of IC50 (μM) obtained in the colon cancer cell lines for the different drugs are summarized in the table. The results of the RT-PCR revealed the presence of P-Glycoprotein in HCT15 and the absence of expression of this protein in the rest of the cell lines studied. The sensitivity to 5-FU and GMZ in the studies seems to correspond to the wt forms of p53 and SMAD4, this last closely related to p21. OXA sensitivity is related to the mutated forms of p53 and SMAD4. IRI is related to the degree of tumor cell differentiation, the most undifferentiated being more sensitive (CMS 1 and 4). IRI, PEM and TRABECT sensitivity is linked to the wt form of APC. In the case of ERIB, the most resistant line is the one that expresses P-glycoprotein.
T84 HCT15 SW480 HT29 2,76 6,23 6,57 8,6 6,06 2,47 2,44 1,77 18,24 9,61 4,24 22,15 0,21 0,3 0,4 0,61 0,24 0,21 0,06 0,31 0,00097 > 0,0075 0,00010 0,00090 0,00140 0,00170 0,00045 0,00200 RAS mut RAS mut RAS mut BRAF mut wt mut mut mut MSS MSI MSS MSS mut mut mut mut mut mut wt mut wt wt wt mut 2 (differentiated) 1 (undifferentiated) 4 (undifferentiated) 3 (differentiated)
Conclusions
1. The sensitivity to fluoropyrimidines is not related to the instability of microsatellites in the cell lines studied. 2. Sensitivity to different drugs correlates with different molecular markers in each case. 3. These results could help to choose the most appropriate treatments in advanced colon cancer and even when the basic therapeutic lines have been exhausted.
Legal entity responsible for the study
SAS.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
35P - Exploring a machine learning approach to predict tumour type from targeted panel DNA sequence data
- Liwen Xiong (Shanghai, China)
Abstract
Background
Some tumour types carry specific genomic alterations, and genomic alterations across numerous different cancers may guide the inference of tumour origin. Therefore, we have explored the feasibility of identifying tumour type based on genomic alterations.
Methods
To predict tumour site of origin, 11867 cases were included in this study. We constructed a random forest classifier using a training cohort of 9493 patients representing 21 cancer types, and the best parameters were determined from 5-fold cross-validation of the training data. Genomic profiling of DNA was performed on formalin-fixed paraffin-embedded tumour samples through NGS with a panel of 381 cancer-related genes.
Results
In our test set of 2374 patients, we accurately predicted tumour type in 1163 cases (49.0% of cases) based on 5-fold cross-validation. The positive predictive value was highest in tumour types with distinctive molecular profiles, or larger sample size (e.g. lung cancer).
Conclusions
These results suggest that the application of artificial intelligence has the potential to predict tissue of origin for a tumour by using mutation data.
Legal entity responsible for the study
Shanghai Chest Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
36P - The dual role of nicotine in breast cancer
- Daud Hossain Khan (Dhaka, Bangladesh)
Abstract
Background
Nicotine, one of the core components of tobacco smoke, has been correlated with cancer progression and tumorigenesis in breast cancer. However, the exact mechanism involved remains under heavy debate as different groups have yielded different possible pathways with α7 and α9 being rooted as the potential key mediators of nicotine. Lack of genomic data, use of extreme high concentrations of nicotine and lack of explanation of such further aggravates matters. In this study, we aim to elucidate the role of α9 nAChR/ CHRNA9 as the pivotal receptor for mediating nicotine-induced effects in breast cancer and explore the possible effects of clinically relevant concentrations of nicotine in transitory ER stress and EMT induced by TGF-β1 in breast cancer.
Methods
Real-time PCR was used to evaluate possible expression of CHRNA9 in breast cancer cell-lines MCF-7 and MDA-MB-231. ER stress response and subsequent dose-evaluation of nicotine was then conducted by treating MCF-7 cells with 5 μg/ml tunicamycin for 24 hours. Experimental groups were co-treated with nicotine concentrations of 50 nM, 250 nM and 500 nM respectively. Viability of these MCF-7 cells were done using standard WST-1 assay. For induction of EMT, MCF-7 cells were treated with 10 ng/ml TGF-β1 for 3 days. Experimental groups consisted of co-treatment with low-dose nicotine (TGF-β1 + nicotine), low-dose nicotine and CHRNA9 antagonist methyllycaconitine (TGF-β1+nicotine+MLCN), low dose nicotine only and 10μM nicotine. Subsequent expression of different EMT and ER stress markers were evaluated using western blotting.
Results
Real-time PCR analysis revealed moderate expression of CHRNA9 in untreated MCF-7 and MDA-MB-231 cells with a 3-4 fold increase after TGF-β1 treatment (p<0.001). Action of nicotine is dose dependent as 500nM of nicotine alleviates both tunicamycin-induced ER stress (p< 0.05) and basal ER stress in MCF-7 cells (p<0.05) while 10μM increases ER stress and rapidly induces EMT in MCF-7 cells (p<0.001). No significsnt effects are observed during EMT for low-dose nicotine groups. However, CHRNA9 levels increase steadily with increasing mesenchymal-phenotype markers.
Conclusions
In conclusion, our data suggests that the action of nicotine is entirely mediated via CHRNA9 and subsequent pathway is entirely dose-dependent.
Legal entity responsible for the study
Department of Bioengineering, George Mason University.
Funding
Department of Bioengineering, George Mason University.
Disclosure
All authors have declared no conflicts of interest.
37P - Melatonin reverses the Warburg-dependent effect in ovarian cancer cell by binding to the MT1 and MT2 receptors
- Luiz Gustavo Chuffa (Botucatu, Brazil)
Abstract
Background
Ovarian cancer (OC) grows rapidly and one of the features associated with its aggressivenes rely on the glycolytic metabolism; unsuccessfully, therapeutic targeting of glycolysis has failed due to the lack of selective, effective and safe inhibitors. Melatonin is an indolamine that display a number of anti-tumor effects via different mechanisms that are dependent or independent of its receptors MT1 and MT2. We therefore evaluated the role of melatonin in reversing the Warburg effect in human OC cells and if the actions are MT1/2 mediated.
Methods
We treated OC SKOV-3 cells, possessing intact or silenced MT1/2 by siRNA, with increasing doses of melatonin (1600, 3200 and 4000μM after 48h exposure) and measured the migration rate and apoptosis by flow citometry. We further analyzed glucose consumption, lactate release and lactate dehydrogenase (LDH) activity through functional assays.
Results
Cell viability was reduced after melatonin exposure regardless the presence of MT1/2 and only the highest dose of 4000 μM attenuated the migration rate; conversely, the silenced cells showed a dramatic reduction in migration (<25% versus control). Apoptosis rate was increased in a dose-dependent manner after melatonin treatment; necrosis was higher following the higher doses of 3200 μM e 4000 μM. Q glucose consumption was decreased after 4000 μM melatonin in contrast to an elevation after MT1/2 knockdown. OC cells showed lower Q lactate releasing after treatment with 3200 μM melatonin while MT1/2 knockdown had an opposite effect; LDH activity was reduced in the presence of MT1/2 rather than increased in silenced cells after treatment with higher doses of melatonin.
Conclusions
Melatonin decreased the migratory potential of ovarian cancer cells in addition to inducing apoptosis regardless of the presence of MT1/2 receptors. These effects are partially attributted to the reversion of glycolytic phenotype of OC cells through binding of melatonin to the MT1/2 receptors.
Legal entity responsible for the study
Institute of Biosciences of Botucatu.
Funding
FAPESP (grant number: 2019/00906-6, 2018/15797-5).
Disclosure
All authors have declared no conflicts of interest.
38P - Study on human plasma concentration and serosal permeation of oral apatinib mesylate
- Jian Shi (Shijiazhuang, China)
Abstract
Background
To explore the characteristics of plasma drug concentration and the possibility of drug passing through the serosa by oral administration of apatinib mesylate (APA-M, 250mg qd).
Methods
36 patients were included: lung adenocarcinoma (n=6), small cell lung cancer (n=12), gastric cardia adenocarcinoma (n=4), others (n=14). There were 5 patients with pleural effusions and 1 patient with peritoneal effusion. Plasma specimens of 36 patients were collected. At 7:40 am, fasting blood was drawn as plasma trough concentration (Cmin). At 8 am, APA-M (250mg qd) was orally administrated. At 11 am, venous blood was drawn as plasma peak concentration (Cmax). Each patient has Cmin and Cmax samples, and different patients have different amounts of samples. A total of 100 plasma samples were obtained. On the same day of plasma collection, 6 patients with serous cavity effusion were retained serous cavity catheter drainage. There were 13 pleural effusions samples (different patients have different amounts of samples) and 1 peritoneal effusion samples. The concentration of APA-M in plasma and serous cavity effusion was determined by UPLC-MS/MS.
Results
1) Steady-state of plasma drug concentration were achieved by day 4. The steady-state trough concentration (Css.min) and peak concentration (Css. max) was 357.7-727.6 ng/ml and 357.7-727.6 ng/ml, respectively. The average Css. max and Css.min was 528.3 ± 66.1 ng/ml and 276.9 ± 42.5 ng/ml, respectively. 2) APA can be detected in serous cavity effusion by day 2, and the effusion drug concentration was 3.14-84.5 ng/ml. After continuous administration for more than 10 days, the ratio of effusion to plasma was 12.7%-152.0%. The average amount of drug permeated in the effusion during each administration was 0.21-4.45 ug.
Conclusions
In clinical practice, the plasma drug concentration of APA reaches steady state quickly by oral administration (250mg qd) with small fluctuation range between peak and trough, and there is no significant drug accumulation during the long-term administration, which leads to a tolerable safety. APA can enter the effusion through the serosa, and the concentration of the drug has a cumulative trend, which can reach a higher drug concentration in the effusion finally.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
39P - Analysis of bloodstream infections in oncological patients
- Mariola Blanco Clemente (Majadahonda, Spain)
Abstract
Background
Information regarding blood stream infections (BSI) in oncological patients is scarce. We studied retrospectively all admitted oncological patients who presented an episode of BSI.
Methods
Our institution is a 613-bed tertiary teaching hospital in Madrid, with a 20-bed Oncology ward. We recorded retrospectively epidemiological, clinical and microbiological data from all BSI from January 2015 to December 2018. We considered CRB both according to IDSA definition and to CDC definition (CLABSI).
Results
We recorded 124 BSI in 107 patients (33 per 1000 oncological admissions) during the study period. Most of them occurred in patients with cancer at metastatic stage (88%), mainly colorectal cancer (25%) and bilio-pancreatic tumors (19%). Other less frequent etiologies were gynecological tumors (15%), lung cancer and lymphomas (9%). Most of the patients (73,4%) were undergoing chemotherapy at the moment of the BSI, 6.5% targeted therapies and 2.4% immunotherapy; 14% were receiving other treatments such as radiotherapy, hormone therapy or palliative care. Only 10.5% of the patients were neutropenic below 500 neutrophils. BSI was healthcare-associated in 42.7% and hospital-acquired in 46.8%. Catheter was the main source (29%; 46% among patients with central venous line), followed by primary (23%) and intra-abdominal source (22%). Gram negative microorganisms were the most prevalent (34.7%), followed by Staphylococci (29.8%). Among 155 isolated microorganisms, 8.4% were MDR. Complications occurred in 5.6% and 4% required ICU admission. In-hospital mortality was 12%, attributable mortality and 10-day mortality were both 4%. When patients with CRB and non-CRB episodes were compared, the independent differential characteristics were as follows: in CRB patients, the most prevalent microorganisms were gram positive (77.8% vs. 38.6%, OR 5.2, p =0.001), persistence of BSI was more common (33.3% vs. 11.4%, OR 3.2, p =0.032) and so was recurrence (13.9% vs. 1.1%, OR 16.4, p=0.022).
Conclusions
The main source of BSI in admitted oncological patients in our centre is catheter. Patients with CRB present persistent and recurrent bacteremia more often, so to prevent bacteremia and its complications, catheter management should be optimized. Attributable mortality in our study was 4%.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
40P - Trends of elevated cancer prevalence among inhabitants of agrarian landscapes in Punjab, Northwestern India
- Parteek Bajwa (Noida, India)
Abstract
Background
Previous studies have predicted that there will be over ten million cancer related annual mortalities worldwide by 2020 and more than 50% of these will be from developing countries. Punjab is considered to be one of the most prosperous states of India since its success during the green revolution. More than 65% of the population of Punjab reside in rural areas and are directly or indirectly involved in farming or related practices. The local people are vulnerable to dust, carcinogens (through heavy pesticides), solar radiation, zoonotic viruses and unhygienic conditions which increases their risk of cancer. Over the last decade, increased incidence of cancer cases had been reported in the rural landscapes of Punjab.
Methods
A detailed cross-sectional study was designed and carried out in 22 districts of Punjab covering an area of 50362 sq km. The districts were further grouped according to socio-economic conditions, cropping pattern and source of drinking water. Household surveys (by trained surveyors) and laboratory investigations for heavy metals and pesticide residual analysis in water, vegetables, fruits, blood and urine were conducted from April 2018 to March 2019.
Results
It was observed that the cancer of the female reproductive system, i.e., breast, cervix and ovary, was overall the highest prevailing cancer category throughout Punjab, followed by cancers of bones, blood & lymphatic system. Data on the relative characteristics of individuals from the locations where cancer or cancer-related deaths existed, showed that involvement in cultivation with pesticide use, alcohol consumption and smoking were prevalent among almost all the regions of the study area. The qualitative analysis confirmed the presence of higher levels of As, Cr, Se and Hg in drinking water, and heptachlor & chlorpyrifos in vegetables, blood and surface water in significant districts (n = 19) of Punjab. Various camps and public awareness programmes were organized to discourage the indiscriminate use of pesticides and alcohol for cancer prevention.
Conclusions
Cancer cases and deaths are significantly higher in some districts of Punjab compared to the National average of India, probably due to a mix of risk factors as mentioned above.
Legal entity responsible for the study
The authors.
Funding
Department of Science and Technology.
Disclosure
All authors have declared no conflicts of interest.
41P - Incidence of cancer, trend with the age and distribution among the cities in Kosovo
- Brunilda P. Profka (Pristina)
Abstract
Background
Cancer incidence rates are increasing among Kosovo young population, likely due to the changes in risk factors caused by globalization. We have still lowest incidence rates in Balkan. But do we have lowest rate because of the median age of population is still young or due to the lack of national screening programs for main type of cancer such as breast, colon or cervical cancer. Appraisal of cancer trends can direct cancer control and public health planning but relevant studies in Kosovo are scarce due to a lack of long-term data. We are evaluating for the first-time data of two last years from cancer registry of Oncology Clinic from University Hospital Centre of Kosovo because this is the only Oncologic center in the whole country.
Methods
Data of cancer incidence were collected by the Oncologic Clinic in University Clinic Center of Kosovo as the only on oncologic center of the country. Age standardized rates (ASRs) for incidence were calculated using the world standard population. GIS system and represented on dynamic dashboard.
Results
A total of 1479 cancer cases were registered in 2018 excluding the hematopoietic malign pathologies from them 339 were breast cancer, 208 lung cancer, 175 colorectal cancer, 169 gynecological cancer, 208 urogenital cancer, 37 head and neck and others. During 2019 were registered a total of 1583 cancer cases from them were 370 breast cancer, 211 lung cancer, 185 colorectal cancer, 212 gynecological cancer, 200 urogenital cancer, 41 head and neck and others.
Conclusions
We have to establish a standardized cancer data registry, to have an electronic system which collect data in the proper way without mistakes. Effective, appropriate and affordable cancer prevention and control strategies are urgently needed in Kosovo for breast, colon and cervical cancer.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
42P - Genetic polymorphism of lncRNA PCAT1 and gastric cancer risk
- Eun Heui Jin (Daejeon, Korea, Republic of)
Abstract
Background
Gastric cancer (GC) is one of the most common cancers in the world. The aims of this study were to evaluate the association between a polymorphism rs710886 in long noncoding RNA (lncRNA) prostate cancer-associated transcript 1 (
Methods
Genotyping of rs710886 was conducted by using TaqMan genotyping assay with 460 GC patients and 377 controls.
Results
After adjusted for age and gender, the rs710886 was associated with an increased risk of GC in subjects aged ≥60 years (dominant model: adjusted OR = 1.68, 95% CI = 1.04-2.72,
Conclusions
Our findings suggest that the rs710886 in lncRNA
Legal entity responsible for the study
The author.
Funding
National Research Foundation of Korea.
Disclosure
The author has declared no conflicts of interest.
43P - Usefulness of the Framingham risk score to predict cardiotoxicity in breast cancer patients
- Mohammed A. Saidi (Tlemcen, Algeria)
Abstract
Background
Breast cancer survival is improving due to combination therapy. However, in the long term, patients may experience negative effects on cardiovascular function. The Framingham score (FRS) provides an estimate of the risk of developing a cardiovascular event, and stratifies patients into low-, intermediate, or high-risk groups. The aim of this study is to evaluate the power of the FRS to predict long-term cardiotoxicity.
Methods
We used echocardiography to evaluate cardiac function in women who had already been treated in our department at least two years ago. FRS was estimated by a validated risk calculator. Patients were stratified into low (<10%), intermediate (10-20%) and high (≥20%) risk groups. Cardiotoxicity was defined by presence of symptomatic congestive heart failure (CHF) or a drop of 5% or more in the left ventricular ejection fraction (LVEF) value without clinical symptoms of CHF.
Results
One hundred Forty-three patients were evaluated for cardiotoxicity after a median follow-up of 9 years (range from 2 to 22 years). 99 patients (69%) were classified as low-risk; 31 (22%) as intermediate risk; and 13 (9%) were classified as high risk. Patients had received multimodal treatment (Anthracyclines:100%, Docetaxel:62,9%, Endocrine therapy: 72%, Trastuzumab: 7%, Radiotherapy: 83,2%). 39 women (28,3%) developed cardiotoxicity, of whom Only one developed symptomatic CHF. Cardiotoxicity was significantly higher in high-risk than in low risk patients (odds ratio: 4,912; 95% confidence interval: 1,48-16,30). ANOVA analysis revealed that Linear regression analysis was statistically significant: High FRS was associated with cardiotoxicity (
Conclusions
Estimation of baseline FRS is of paramount importance; it can predict the risk of cardiotoxicity in long-term cancer survivors. It can be used to perform a baseline risk stratification, to allow personalized cardiac monitoring, and why not to guide cardioprotective therapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
44P - Role of DNA methylation and non-coding RNA in INK4b-ARF-INK4a locus expression
- Guillaume Latgé (Liège, Belgium)
Abstract
Background
In breast cancer, the oestrogen receptor expressing subtype (ER+) is the most frequent. Those tumours frequently become resistant to hormonotherapy and metastasise. In this case, chemotherapy needs to be administrated. The CDK4/6 inhibitors in combination with hormonotherapy are the new standard treatment for metastatic disease and allows the postponement of chemotherapy. These drugs play the same role as the endogenous p16-p15 proteins, and patients who have lost expression of these proteins are expected to be those who will respond best to treatment. However, none of the currently tested biomarkers are predictive of treatment response. The INK locus, where p16/p14-p15 proteins are encoded, is involved in the cell cycle and is often altered in cancers. Expression of p16/p14-p15 is negatively regulated by ANRIL, a non-coding RNA (ncRNA). ANRIL interacts with Polycomb Repressive Complexes and guides them to methylate and silence this locus. In cancer, aberrant methylation is involved in tumorigenesis. Understanding the molecular mechanisms between ncRNA and regulation of the expression of p16/p14-p15 may highlight potential biomarkers of treatment response in ER+ breast cancer.
Methods
Results
MDAMB468 (triple negative) and T47D (ER+) cells show different methylation and expression profiles, showing a link between the expression of the locus and its methylation. ANRIL and methylation of gene promoters influence locus silencing. DNA methylation around or after the stop codon of a gene are poorly described in the literature but seem to also play a role in regulation of RNA expression. RNAseq reveals little-known transcripts highly expressed in MDAMB468; it’s possible effect and its relevance
Conclusions
Understanding the role of DNA methylation and ncRNA in this locus could help to adapt and identify effective treatments in ER+ breast cancer.
Legal entity responsible for the study
University of Liège.
Funding
F.R.S-FNRS.
Disclosure
All authors have declared no conflicts of interest.
45P - Comparative expression profiling of miR-21, -155 and -221 in benign and malignant breast tumours
- Nida Matloob (Islamabad, Pakistan)
Abstract
Background
Breast cancer (BC) is one of the most common cancer types reported worldwide. Benign breast tumours such as fibroadenomas (FBA) share certain features with cancerous cells and constitute major proportion of reported cases of breast-associated malignancies yet the in-depth molecular mechanisms contributing to benign tumours remains least explored. Dysregulation of microRNAs (miRNAs) is shown to play an important role in pathogenesis of BC however, the information on expression patterns and involvement of miRNAs in benign tumours of breast remains largely unknown. The present study aimed at performing comparative expression profiling of a panel of miRNAs (miR-21, -155, -221) that are known to exhibit oncogenic, tumour-suppressor, proliferation and immunogenic properties in a well-established breast tissue cohort of type; benign, malignant and non-cancerous (paired adjacent).
Methods
The study cohort comprised of 121 participants (pre-operative/treatment-naive BC (n) = 69; FBA (n) = 52). The expression levels of selected miRNAs were measured via qPCR. Receiver operating characteristic curve analysis was performed to determine the diagnostic potential of miRNAs.
Results
The expression level of all three miRNAs, miR-21, -155 and -221 was significantly upregulated in BC vs. adjacent non-tumour tissues (
Conclusions
miR-21, -155, and -221 panel have the potential to serve as malignancy specific-markers in breast tumours. It is expected that the findings of present study will help in understanding role of miRNAs information and progression of benign and malignant breast tumours. Further studies are underway to determine non-invasive biomarker potential of these miRNAs in discriminating early-stage BC and FBA patients.
Legal entity responsible for the study
Nida Matloob.
Funding
COMSATS University Islamabad (CUI).
Disclosure
All authors have declared no conflicts of interest.