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Cancer Statistics
Population in 2012: 1.1m
People newly diagnosed with cancer (excluding NMSC) / yr: 3,400
Age-standardised rate, incidence per 100,000 people/yr: 204.7
Risk of getting cancer before age 75:20.6%
People dying from cancer /yr: 1,500
Data from IARC GlobalCan (2012)
Cyprus Cancer Organisations and Resources
Latest Research Publications Related to Cyprus

Cyprus Cancer Organisations and Resources (4 links)

Latest Research Publications Related to Cyprus

Kouriefs C, Georgiades F, Michaelides M, et al.
Percutaneous hook wire assistance during laparoscopic excision of an intrarenal mass.
Ann R Coll Surg Engl. 2019; 101(6):e136-e138 [PubMed] Free Access to Full Article Related Publications
Completely endophytic renal tumours pose challenges in laparoscopic nephron-sparing tumour excisions, with the use of intraoperative imaging techniques (e.g. ultrasound) being crucial when managing such tumours. The use of a percutaneous hookwire for tumour localisations are in use in several other surgical fields, such as breast surgery. An asymptomatic 52-year-old man presented with an incidental small right sided solid 33-mm interpolar renal mass identified on computed tomography. A guided insertion of a percutaneous localisation wire was carried out prior to a laparoscopic partial nephrectomy to assist in intraoperative tumour landmark/margins identification. Operative time was 210 minutes with zero ischaemia time, with an estimated blood loss of 200 ml. No perioperative complications were observed and the patient was discharged two days postoperatively. Histology revealed the mass to be a Fuhrman grade 2 clear-cell carcinoma with a 2-mm clear surgical margin. The patient remained free of recurrence at 16 months of follow-up. We have reported our first experience of wire localisation prior to laparoscopic partial nephrectomy for an intrarenal mass, which to our knowledge could be the first of its kind in renal surgery. Percutaneous wire localisation of endophytic renal tumours is potentially safe and effective and can allow nephron-sparing surgery where laparoscopic ultrasound is not available. Longer-term and further evidence should be encouraged.

Harikrishna A, Ishak A, Ellinides A, et al.
The impact of obesity and insulin resistance on thyroid cancer: A systematic review.
Maturitas. 2019; 125:45-49 [PubMed] Related Publications
In recent decades, there has been a marked increase in the prevalence of thyroid cancer. This phenomenon has paralleled the increase in the prevalence of obesity worldwide, which is associated with insulin resistance. Associations between these entities have been hypothesized, mainly for older and female populations, but they remain unclear. The aim of this article is to systematically review the literature in an attempt to determine whether the increase in the prevalence of thyroid cancer is due to obesity or due only to improved detection with the better imaging techniques available. A thorough literature search on PubMed and application of selection criteria identified 15 appropriate studies. The detailed analysis of the data from these studies indicated that there is a suggestive association between thyroid cancer, obesity, insulin resistance and hyperinsulinemia for both genders. Therefore, the increased prevalence of thyroid cancer is not dependent on improved detection only. Further research should be performed for complete understanding of the pathophysiological associations, especially regarding adipose tissue and genetics, but also for the improvement of preventive public health policies.

Angelou A, Antoniou E, Pikouli A, et al.
Platelet Depletion/Transfusion as a Lethal Factor in a Colitis-associated Cancer Mouse Model.
Anticancer Res. 2019; 39(5):2443-2446 [PubMed] Related Publications
BACKGROUND/AIM: TLR-4 Knock-out (KO) mice are protected from colitis-associated cancer in the established AOM/DSS mouse model. The aim of this study was to assess whether the TLR4 KO mice would still be protected from carcinogenesis after platelet depletion and transfusion with TLR4 wild-type platelets.
MATERIALS AND METHODS: Thirty-two female C57BL6 mice were divided into 6 groups. Among the three groups that received Azoxymethane/Dextran Sulfate Sodium (AOM/DSS), one group included TLR4KO mice, which were depleted of their platelets and were then transfused with platelets from TLR4 wild-type mice. The other two groups included wild-type and TLR-4KO mice that only received AOM/DSS.
RESULTS: All 6 animals in the KO group that underwent platelet depletion/transfusion succumbed. Three of them died before the administration of DSS and three in the week following DSS administration. In contrast, mice in the other two groups experienced less weight loss and only 1 mouse died in each of them.
CONCLUSION: Platelet depletion/transfusion was detrimental in TLR-4 transgenic mice that received AOM/DSS.

Petrou S, Mamais I, Lavranos G, et al.
Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials.
Int J Vitam Nutr Res. 2018; 88(1-2):100-112 [PubMed] Related Publications

Ferreira MA, Gamazon ER, Al-Ejeh F, et al.
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.
Nat Commun. 2019; 10(1):1741 [PubMed] Free Access to Full Article Related Publications
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Charalambous A, Berger AM, Matthews E, et al.
Cancer-related fatigue and sleep deficiency in cancer care continuum: concepts, assessment, clusters, and management.
Support Care Cancer. 2019; 27(7):2747-2753 [PubMed] Related Publications
Throughout the cancer continuum, patients are faced with the cancer- and treatment-related side effects that can have a negative impact on their overall quality of life. Cancer-related fatigue (CRF) and sleep deficiency are among the symptoms that patients and their caregivers most often experience. An increasing body of literature suggests that a strong correlation between CRF and sleep deficiency exists, indicating that they may be reciprocally related and that they may have similar underlying etiology. This paper aims at bringing together the opinions of leading cancer control (i.e., CRF and sleep) and oncology experts in order to increase the understanding of CRF and sleep deficiency's assessment, associated symptom clustering, symptom burden shared by caregivers, and CRF and sleep deficiency management in the cancer care context.

Abbasi A, Sadikoglu F, Hassanzadeh M
Effect of Au-197 nanoparticles along with Sm-153 radiopharmaceutical in prostate cancer from simulation method.
J Cancer Res Ther. 2019; 15(Supplement):S42-S46 [PubMed] Related Publications
Aims: Based on recent studies, it was indicated that gold (Au-197) nanoparticles could be safely prescribed and used to enhance the absorbed dose during radiation therapy.
Subjects and Methods: We evaluated the samarium-153 (Sm-153) radiopharmaceutical and Au-197 and Sm-153 radiopharmaceutical absorbed dose rate by means of the Monte Carlo technique in prostate cancer.
Results: The results show that absorbed dose rate in entire prostate volume due to 20 mCi of Sm-153 radiopharmaceutical is 27.339 μGy/s, 48.837 μGy/s, and 76.176 μGy/s for γ-interaction, β¯ particle interaction, and γ+β¯ interaction, respectively. The results in the exterior of the prostate for β¯ interaction, β¯ particle interaction, and γ+β¯ interaction were 20.971 μGy/s, 1.110 μGy/s, and 22.081 μGy/s, respectively.
Conclusions: The calculation results for Au-197 and Sm-153 radiopharmaceutical show that the absorbed dose rate in entire prostate volume 3% was increased and undesirable dose value in exterior of prostate 7% was decreased.

Tuncel G, Kalkan R
Importance of m N
Med Oncol. 2019; 36(4):36 [PubMed] Related Publications
RNA methylation, which was identified back in 1970s, has gained remarkable interest in recent years as it was shown to be a reversible modification involved in many cellular processes like mRNA and miRNA processing, mRNA localisation, translation suppression, or activation. These, in turn, affect important bioprocesses such as tissue development, sex determination, and DNA damage response. Important group of proteins are responsible for adding, recognizing, and removing the methyl group to and from the RNA molecules, which are referred as writers, readers, and erasers, respectively. If any of the processes is not strictly controlled, this can cause abnormalities in gene expression, which result in diseases including cancers such as lung, pancreas, glioblastoma, and breast cancer. Mechanisms of RNA methylation and its role in various cancer types and diagnostic methods for RNA methylation are discussed in this article.

Voskarides K
The "cancer-cold" hypothesis and possible extensions for the Nordic populations.
Scand J Public Health. 2019; 47(5):477-481 [PubMed] Related Publications
Cancer incidence is inexplicably high in cold countries. This has been revealed by recent genetic and epidemiological studies. These studies used data from the GLOBOCAN-2012 database, for 186 populations and for a variety of cancer types. Cancer incidence in Nordic people is particularly high for the frequent cancer forms, like breast, prostate and colon cancer. A relationship of cancer with cold is suspected since Inuit and Alaska Indians that live in even more extreme low temperatures have the higher cancer rates in the world. In this article, possible reasons for this phenomenon are discussed. These explanations are related with: evolutionary adaptation to extreme cold, the genetic background of Nordic people, the experimentally proven fast growth and metastasis of tumors at low temperatures, high concentration of certain air pollutants at cold environments, low levels of serum Vitamin D, overdiagnosis by the medical doctors and high quality of the health system in Nordic countries. Lifestyle parameters are not discussed in detail, although these may be equally crucial for cancer risk in cold countries. In conclusion, more studies are needed to elucidate the real causes of this epidemiological pattern.

Krensel M, Schäfer I, Augustin M
Cost-of-illness of melanoma in Europe - a modelling approach.
J Eur Acad Dermatol Venereol. 2019; 33 Suppl 2:34-45 [PubMed] Related Publications
BACKGROUND: Malignant melanoma is accounting for the vast majority of skin cancer death. The treatment and productivity loss due to morbidity or premature mortality are associated with costs for society. There are few cost-of-illness (COI) studies on malignant melanoma in European countries from societal perspective and currently there is no publication analysing the COI in all European countries.
OBJECTIVES: The objective of the present study was to comparatively estimate COI of malignant melanoma in the European countries based on an identical approach.
METHODS: Cost information was obtained from results of a systematic literature research. For countries with no available cost information, a model for imputation of cost data was developed. Country-specific costs were modelled on the national gross domestic product, health expenditures, gross national income and epidemiological data. The adjustment for purchasing power parity allowed a comparison across countries.
RESULTS: Crude national costs of malignant melanoma ranged between € 1.1 million in Iceland and € 543.8 million in Germany and resulted in € 2.7 billion for all EU/EFTA states. Estimated crude costs per patient were lowest in Bulgaria (€ 6422) and highest in Luxembourg (€ 50 734). The share of direct costs varied from 3% to 26% across countries. After adjustment for the purchasing power parity costs per patient ranged between € 14 420 in Bulgaria and € 50 961 in Cyprus. Treatment expenses and morbidity costs were markedly lower for countries that entered the EU since 2004. By contrast, mortality costs were lower in countries with a high gross domestic product per capita.
CONCLUSION: In this first estimation, malignant melanoma induces relevant COI in Europe. There was large variation in the costs per patient due to different health care systems and expenses. Beyond decreasing patient burden, early intervention and prevention of melanoma could have a relevant potential to save costs across Europe.

Hadjipanteli A, Elangovan P, Mackenzie A, et al.
The threshold detectable mass diameter for 2D-mammography and digital breast tomosynthesis.
Phys Med. 2019; 57:25-32 [PubMed] Related Publications
Digital breast tomosynthesis (DBT) is currently under consideration for replacement of, or combined use with 2D-mammography in national breast screening programmes. To investigate the potential benefits that DBT can bring to screening, the threshold detectable lesion diameters were measured for different forms of DBT in comparison to 2D-mammography. The aim of this study was to compare the threshold detectable mass diameters obtained with narrow angle (15°/15 projections) and wide angle (50°/25 projections) DBT in comparison to 2D-mammography. Simulated images of 60 mm thick compressed breasts were produced with and without masses using a set of validated image modelling tools for 2D-mammography and DBT. Image processing and reconstruction were performed using commercial software. A series of 4-alternative forced choice (4AFC) experiments was conducted for signal detection with the masses as targets. The threshold detectable mass diameter was found for each imaging modality with a mean glandular dose of 2.5 mGy. The resulting values of the threshold diameter for 2D-mammography (10.2 ± 1.4 mm) were found to be larger (p < 0.001) than those for narrow angle DBT (6.0 ± 1.1 mm) and wide angle DBT (5.6 ± 1.2 mm). There was no significant difference between the threshold diameters for wide and narrow angle DBT. Implications for the introduction of DBT alone or in combination with 2D-mammography in breast cancer screening are discussed.

Sydney GI, Ioakim KJ, Paschou SA
Insulin resistance and adrenal incidentalomas: A bidirectional relationship.
Maturitas. 2019; 121:1-6 [PubMed] Related Publications
An adrenal incidentaloma (AI) is an adrenal mass incidentally found via a radiological modality, independent of an endocrinological investigation. In this review, we aimed to investigate the possible reasons behind the increased frequency in AI detection, especially in ageing populations. The pathophysiological effects of insulin resistance (IR), hyperinsulinemia and various anabolic pathways are analyzed. In addition, we review data from studies indicating an increased incidence of adrenal adenomas and carcinomas in patients with type 2 diabetes mellitus (T2DM). The establishment of obesity as a global epidemic, with a higher prevalence in the female than in the male population, coincide with data regarding AIs and the conditions may share a pathophysiological basis. Furthermore, we discuss the bidirectional association of AIs with obesity, insulin resistance and T2DM, especially in patients with autonomous cortisol secretion. Lastly, as per the definition of an AI, we touch upon the evolution of radiological imaging as another possible cause of the rise in prevalence of AIs, especially concerning the greater use and precision of computed tomography (CT).

Voutouri C, Kirkpatrick ND, Chung E, et al.
Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies.
Proc Natl Acad Sci U S A. 2019; 116(7):2662-2671 [PubMed] Free Access to Full Article Related Publications
Cooption of the host vasculature is a strategy that some cancers use to sustain tumor progression without-or before-angiogenesis or in response to antiangiogenic therapy. Facilitated by certain growth factors, cooption can mediate tumor infiltration and confer resistance to antiangiogenic drugs. Unfortunately, this mode of tumor progression is difficult to target because the underlying mechanisms are not fully understood. Here, we analyzed the dynamics of vessel cooption during tumor progression and in response to antiangiogenic treatment in gliomas and brain metastases. We followed tumor evolution during escape from antiangiogenic treatment as cancer cells coopted, and apparently mechanically compressed, host vessels. To gain deeper understanding, we developed a mathematical model, which incorporated compression of coopted vessels, resulting in hypoxia and formation of new vessels by angiogenesis. Even if antiangiogenic therapy can block such secondary angiogenesis, the tumor can sustain itself by coopting existing vessels. Hence, tumor progression can only be stopped by combination therapies that judiciously block both angiogenesis and cooption. Furthermore, the model suggests that sequential blockade is likely to be more beneficial than simultaneous blockade.

Kavaz D, Umar H, Shehu S
Synthesis, characterization, antimicrobial and antimetastatic activity of silver nanoparticles synthesized from Ficus ingens leaf.
Artif Cells Nanomed Biotechnol. 2018; 46(sup3):S1193-S1203 [PubMed] Related Publications
Cancer incidence is still increasing due to inadequate responsive treatments. Inertness and biocompatibility of nanoparticles synthesized using plant extracts have shown therapeutic applications and make it to be a good anti-cancer candidates. This study is a recent novel spotlight that synthesized silver nanoparticle from Ficus ingens leaf extract (FILE) and studied its anti-metastatic and anti-bacterial activity. The chemical and surface analysis of the synthesized FILE silver nanoparticles (FILE-AgNPs) was studied using UV-visible, Fourier transform infrared (FTIR), X-ray diffraction (XRD), zeta sizer, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Gas chromatography mass spectrometric (GC-MS) and quantitative photochemical analyses were also carried out. The antimicrobial activity of FILE-AgNPs was found to be effective with MIC of 10 µg/mL for E. coli and 20 µg/mL for S. typhi and B. cereus with significance difference. Toxicity, proliferation and anti-metastatic potential of FILE-AgNPs were studied on MDA-MB 231 cell models using tryphan blue, MTT and wound heal assay, respectively. FILE-AgNPs showed the ability to inhibit metastasis of MDA-MB 231 cells in dose-dependent manner in which 10 μg/mL and 5 μg/mL inhibit by 96% and 75%, respectively. The synthesized FILE-AgNPs are remarkable candidates for treatment of cancer cases and other cancer related cases.

Jiang X, Finucane HK, Schumacher FR, et al.
Shared heritability and functional enrichment across six solid cancers.
Nat Commun. 2019; 10(1):431 [PubMed] Free Access to Full Article Related Publications
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r

Zhao Y, Cao J, Melamed A, et al.
Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma.
Proc Natl Acad Sci U S A. 2019; 116(6):2210-2219 [PubMed] Free Access to Full Article Related Publications
In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (

Alshaikhi J, Doolan PJ, D'Souza D, et al.
Impact of varying planning parameters on proton pencil beam scanning dose distributions in four commercial treatment planning systems.
Med Phys. 2019; 46(3):1150-1162 [PubMed] Related Publications
PURPOSE: In pencil beam scanning proton therapy, target coverage is achieved by scanning the pencil beam laterally in the x- and y-directions and delivering spots of dose to positions at a given radiological depth (layer). Dose is delivered to the spots on different layers by pencil beams of different energy until the entire volume has been irradiated. The aim of this study is to investigate the implementation of proton planning parameters (spot spacing, layer spacing and margins) in four commercial proton treatment planning systems (TPSs): Eclipse, Pinnacle
MATERIALS AND METHODS: Using identical beam data in each TPS, plans were created on uniform material synthetic phantoms with cubic targets. The following parameters were systematically varied in each TPS to observe their different implementations: spot spacing, layer spacing and margin. Additionally, plans were created in Eclipse to investigate the impact of these parameters on plan delivery and optimal values are suggested.
RESULTS: It was found that all systems except Eclipse use a variable layer spacing per beam, based on the Bragg peak width of each energy layer. It is recommended that if this cannot be used, then a constant value of 5 mm will ensure good dose homogeneity. Only RayStation varies the spot spacing according to the variable spot size with depth. If a constant spot spacing is to be used, a value of 5 mm is recommended as a good compromise between dose homogeneity, plan robustness and planning time. It was found that both Pinnacle
CONCLUSIONS: All four systems are capable of delivering uniform dose distributions to simple targets, but their implementation of the various planning parameters is different. In this paper comparisons are made between the four systems and recommendations are made as to the values that will provide the best compromise in dose homogeneity and planning time.

Özay AC, Emekçi Özay Ö, Okyay RE, Gülekli B
The effect of myoinositol on ovarian blood flows in women with polycystic ovary syndrome.
Gynecol Endocrinol. 2019; 35(3):237-241 [PubMed] Related Publications
To evaluate whether 4 gram myoinositol and 400 mcg folic acid(MYO) therapy has any effects on ovarian stromal blood flow by using pulsed and color Doppler at 3 months follow-up period in polycystic ovary syndrome (PCOS). One-hundred eighty patients were designed into six groups; Group 1: PCOS patients that received OCP containing 30 mcg ethinyl estradiol (EE) plus 3 mg drospirenone (DRP); Group 2: PCOS patients that received MYO; Group 3: PCOS patients that received no medication. Group 4: Healthy patients that received OCP; Group 5: Healthy patients that received MYO; Group 6: Healthy patients that received no medication. Resistance index (RI) and pulsatility index (PI) of both ovaries were assessed. There was a significant increase in RI and PI of both ovarian stromal blood flow women with PCOS who received OCP (Group 1, p < .001) and MYO (Group 2, p < .001). The rate of increment in both RI and PI values were similar for OCP users (Group 1) and MYO users(Group2) in PCOS patients. MYO therapy reduced ovarian vascularization in both PCOS and healthy users after 3 months and this decrease is especially noticeable in women with PCOS compared to healthy women. OCP therapy also reduced ovarian vascularization just like MYO therapy.

Gkretsi V, Louca M, Stylianou A, et al.
Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15).
Int J Mol Sci. 2019; 20(1) [PubMed] Free Access to Full Article Related Publications
Extracellular matrix (ECM)-related adhesion proteins are important in metastasis. Ras suppressor-1 (RSU-1), a suppressor of

Papalampros A, Vailas MG, Deladetsima I, et al.
Irreversible electroporation in a case of pancreatic leiomyosarcoma: a novel weapon versus a rare malignancy?
World J Surg Oncol. 2019; 17(1):6 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary pancreatic leiomyosarcoma is an extremely rare entity that needs high clinical suspicion in order to diagnose it at an early stage. Clinical characteristics, diagnosis, and management still remain challenging and controversial, especially in advanced stages, when tumor invades adjacent vessels and organs or gives distant metastases.
CASE PRESENTATION: Herein, we describe a case of a 57-year-old woman suffering from advanced pancreatic leiomyosarcoma with thrombosis of the superior mesenteric vein, as well as liver lesions which were suspicious for metastasis. Multidisciplinary team decided for upfront chemotherapy to assess tumor response. Follow-up imaging after the completion of chemotherapy led tumor board to decide for subsequent surgical exploration. The patient underwent exploratory laparotomy and irreversible electroporation ablation of the pancreatic tumor. Postoperative course was uneventful, and she was discharged 10 days later with a plan to receive adjuvant therapy. To the best of our knowledge, this is the first case of pancreatic leiomyosarcoma ever reported, treated with this novel technique of irreversible electroporation that could be an alternative and feasible way for the management of these rare malignancies.
CONCLUSIONS: In conclusion, primary pancreatic leiomyosarcoma is a rare and highly malignant tumor associated with poor prognosis. Nowadays, R0 surgical resection remains the cornerstone treatment, combined with adjuvant and/or neoadjuvant chemotherapy prior to resection. In the advanced setting, when major vessel invasion and distant metastases occur, chemotherapy along with irreversible electroporation ablation could be a helpful and possibly effective modality for the management of this highly aggressive tumor.

Sebio A, Constantinidou A, Benson C, et al.
Gemcitabine Re-challenge in Metastatic Soft Tissue Sarcomas: A Therapeutic Option for Selected Patients.
Anticancer Res. 2019; 39(1):347-351 [PubMed] Related Publications
BACKGROUND/AIM: Treatment options for patients with metastatic soft tissue sarcomas are limited. Re-challenge with a previously successful gemcitabine-based regimen is common. There are no published data to support this practice.
PATIENTS AND METHODS: We conducted a retrospective search to identify patients re-challenged with gemcitabine-based chemotherapy (GBC) from 2003 to 2015.
RESULTS: Twenty-nine patients re-challenged with gemcitabine were identified. The response rate for initial GBC was 55% (n=15) and for re-challenge GBC 26% (n=6). The median progression-free survival was 11.1 months (95%CI=7.2-11.9) for initial GBC and 5.3 months (95%CI=2.0-7.5) for re-challenge GBC. Overall survival following gemcitabine re-challenge was 12.2 months (95%CI=7.0-18.2). Twelve out of 26 evaluable patients (46%) treated with re-challenge GBC experienced grade 3-4 adverse events (CTCAE 4.03) with 31% (n=8) of patients requiring dose reduction.
CONCLUSION: In selected patients, gemcitabine re-challenge can be considered in advanced sarcomas, however, this approach is associated with toxicity.

Umar H, Kavaz D, Rizaner N
Biosynthesis of zinc oxide nanoparticles using
Int J Nanomedicine. 2019; 14:87-100 [PubMed] Free Access to Full Article Related Publications
Background: Biocompatibility and stability of zinc oxide nanoparticles (ZnO NPs) synthesized using plants is an interesting research area of study in nanotechnology, due to its wide applications in biomedical, industrial, cell imaging, and biosensor fields. The present study reports the novel green synthesis of stable ZnO NPs using various concentrations of zinc nitrate (0.01M, 0.05M, 0.1M) and
Methods: Characterization of the synthesized ZnO NPs were carried out using various spectroscopic and microscopic techniques. Antimicrobial activity evaluation using disc diffusion method, antioxidant activity using hydrogen peroxide (H
Results: The UV-vis spectroscopy result revealed an absorption peak in the range of 370 nm. The involvements of
Conclusion: Overall, various concentrations of ZnO NPs were synthesized through a stable, simple, and eco-friendly green route via the use of

Anker MS, Lena A, Hadzibegovic S, et al.
Modern-day cardio-oncology: a report from the 'Heart Failure and World Congress on Acute Heart Failure 2018'.
ESC Heart Fail. 2018; 5(6):1083-1091 [PubMed] Free Access to Full Article Related Publications
During the 'Heart Failure and World Congress on Acute Heart Failure 2018', many sessions and lectures focused on cardio-oncology. This important field of research is constantly growing, and therefore, a great amount of time during the congress focused on it. Prevention and early recognition of side effects is very important in cancer patients. One of the most common and potentially severe problems during antineoplastic therapy is cardiotoxicity. Hence, cardio-oncology is vital in managing cancer patients. This paper will summarize the topics discussed in three main sessions and many additional lectures throughout the 'Heart Failure and World Congress on Acute Heart Failure 2018'. The covered topics included pathophysiological mechanisms in the development of heart failure, risk factors, and early signs of cardiotoxicity detectable with different circulating and imaging biomarkers, as well as cardioprotective treatments recommended by different guidelines and position papers.

Tzelepis K, De Braekeleer E, Aspris D, et al.
SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4.
Nat Commun. 2018; 9(1):5378 [PubMed] Free Access to Full Article Related Publications
We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.

Day F, Karaderi T, Jones MR, et al.
Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.
PLoS Genet. 2018; 14(12):e1007813 [PubMed] Free Access to Full Article Related Publications
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.

Tüzmen Ş, Hostetter G, Watanabe A, et al.
Characterization of farnesyl diphosphate farnesyl transferase 1 (FDFT1) expression in cancer.
Per Med. 2019; 16(1):51-65 [PubMed] Related Publications
AIM: To help characterize the FDFT1 gene and protein expression in cancer. Cholesterol represents an important structural component of lipid rafts. These specializations can be involved in pathways stimulating cell growth, survival and other processes active in cancer. This cellular compartment can be expanded by acquisition of cholesterol from the circulation or by its synthesis in a metabolic pathway regulated by the FDFT1 enzyme. Given the critical role this might play in carcinogenesis and in the behavior of cancers, we have examined the level of this enzyme in various types of human cancer. Our demonstration of elevated levels of FDFT1 mRNA and protein in some tumors relative to surrounding normal tissue identifies this as a possible biomarker for disease development and progression, and as a potential new target for the treatment of cancer.

Becer E, Hanoğlu DY, Kabadayı H, et al.
The effect of Colchicum pusillum in human colon cancer cells via Wnt/β-catenin pathway.
Gene. 2019; 686:213-219 [PubMed] Related Publications
OBJECTIVE: Colchicum pusillum belongs to the family Colchicaceae that particularly rich in tropolonic alkaloids. The aim of this study was to investigate the cytotoxicity and in vitro anticancer activity of Colchicum pusillum ethanolic extract on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines.
MATERIALS AND METHODS: Colchicum pusillum was collected and extracted with ethanol. Different concentrations of Colchicum pusillum extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assays. Anticancer and antiproliferative activities of Colchicum pusillum were investigated by immunocytochemistry using antibodies directed against to β-catenin, Ki-67, LGR-5 Ki-67, DKK1, Frizzled-4, Wnt4, Wnt7a and caspase3 in Colo-741 cells.
RESULTS: All concentrations of Colchicum pusillum extract had toxic effect in Colo-320 cells. Because of this, we used Colchicum pusillum extract at 20 μg/ml for evaluate anticancer activities only in Colo-741 cells. As a result of immunohistochemical staining, β-catenin, LGR-5 and caspase-3 immunoreactivities were significantly increased while Wnt7a immunostaining intensity was decreased in Colo-741 cells. Conclusion We conclude that Colchicum pusillum extract increased β-catenin and LGR-5 via Wnt/β-catenin pathway in colon cancer cells. Interestingly, it decreased other signaling molecule, Wnt7a which is assumed to play protective role during carcinogenesis. Also, it increased significantly caspase-3 immunoreactivity showing that apoptotic pathways were triggered.

Doğan Şiğva ZÖ, Balci Okcanoğlu T, Biray Avci Ç, et al.
Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines.
Gene. 2019; 687:261-271 [PubMed] Related Publications
Paclitaxel, which isolated from Taxus brevifolia, is recently started to be used against prostate cancer treatment and it is a very effective compound against cancer. In this study, we aimed to test the synergistic effect of two plant active compounds (sulphoraphane (SFN) and silymarin (SILY)) and several endemic plant species from Turkey (such as Phlomis leucophracta, Rubia davisiana, Alkanna tinctoria), which are known to have anticarcinogenic effect on androgen-independent PC3 and DU145, and androgen-dependent VCaP prostate cancer cell lines, with paclitaxel on the expression of cell cycle signaling and apoptosis regulator genes. Herbal substances and endemic herbal extracts were combined with Paclitaxel drug. IC

Stylianou A, Lekka M, Stylianopoulos T
AFM assessing of nanomechanical fingerprints for cancer early diagnosis and classification: from single cell to tissue level.
Nanoscale. 2018; 10(45):20930-20945 [PubMed] Related Publications
Cancer development and progression are closely associated with changes both in the mechano-cellular phenotype of cancer and stromal cells and in the extracellular matrix (ECM) structure, composition, and mechanics. In this paper, we review the use of atomic force microscopy (AFM) as a tool for assessing the nanomechanical fingerprints of solid tumors, so as to be potentially used as a diagnostic biomarker for more accurate identification and early cancer grading/classification. The development of such a methodology is expected to provide new insights and a novel approach for cancer diagnosis. We propose that AFM measurements could be employed to complement standard biopsy procedures, offering an objective, novel and quantitative diagnostic approach with the properties of a blind assay, allowing unbiased evaluation of the sample.

Roointan A, Ahmad Mir T, Ibrahim Wani S, et al.
Early detection of lung cancer biomarkers through biosensor technology: A review.
J Pharm Biomed Anal. 2019; 164:93-103 [PubMed] Related Publications
Lung cancer is undoubtedly one of the most serious health issues of the 21 st century. It is the second leading cause of cancer-related deaths in both men and women worldwide, accounting for about 1.5 million deaths annually. Despite advances in the treatment of lung cancer with new pharmaceutical products and technological improvements, morbidity and mortality rates remains a significant challenge for the cancer biologists and oncologists. The vast majority of lung cancer patients present with advanced-stage of pathological process that ultimately leads to poor prognosis and a five-year survival rate less than 20%. Early and accurate screening and analysis using cost-effective means are urgently needed to effectively diagnose the disease, improve the survival rate or to reduce mortality and morbidity associated with lung cancer patients. Thus, the only hope for early recognition of risk factors and timely diagnosis and treatment of lung cancer is biosensors technology. Novel biosensing based diagnostics approaches for predicting metastatic risks are likely to have significant therapeutic and clinical impact in the near future. This article systematically provides a brief overview of various biosensing platforms for identification of lung cancer disease biomarkers, with a specific focus on recent advancements in electrochemical and optical biosensors, analytical performances of different biosensors, challenges and further research opportunities for routine clinical analysis.

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