Michael Koukourakis

Democritus University of Thrace | DUTH · Κλινική Ακτινοθεραπευτικής Ογκολογίας

The IFN-type-I pathway is involved in radiotherapy (RT)-mediated immune responses. Large RT fractions have been suggested to potently induce this pathway. Neoadjuvant hypofractionated short-course (scRT) and conventional long-course (lcRT) RT applied for the treatment of locally advanced rectal adenocarcinoma patients provides a unique model to add...

Introduction: The role of the immune system in the efficacy of radiotherapy (RT) has been well established. We examined the role of neoplasia-related and treatment-induced lymphopenia in the outcome of RT or chemoradiotherapy (CRT) in squamous cell laryngeal cancer. Materials and methods: We retrospectively analyzed a series of 135 laryngeal car...

Studying the levels of cytokines in the plasma of patients could be valuable in guiding immunotherapy policies. We assessed the plasma levels of 4 major cytokines [interferon (IFN)-β, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β)] collected from 19 patients with ductal breast cancer (BCa), before...

Simple Summary Concurrent administration of anti-PD-1 immunotherapy with one or two fractions of ultra-hypofractionated (8 Gy/fraction) radiotherapy for patients with locoregionally recurrent non-small cell lung cancer (NSCLC) after radical chemo-radiotherapy was examined in a cohort of 11 patients. This immuno-radiotherapy scheme was safe and prov...

Using next-generation sequencing (NGS), we investigated DNA mutations in the plasma tumor cell-free circulating DNA (ctDNA) of 38 patients with inoperable squamous cell head neck cancer (SCHNC) before and after the completion of chemoradiotherapy (CRT). Baseline mutations of the TP53 were recorded in 10/38 (26.3%) and persisted in 4/10 patients aft...

Background/aim: The plasma levels of cell-free DNA (cfDNA) in cancer patients increase due to rapid cancer cell proliferation and death. Therefore, cfDNA can be used to study specific tumor-DNA features. In addition, the non-specific cfDNA concentration may be an important biomarker of cancer prognosis. Patients and methods: We prospectively exa...

Circulating cell-free DNA (cfDNA) in the blood of cancer patients contains tumor-specific mutated genes and viral genome that can be identified and quantified as ‘tumor-specific cfDNA’ (circulating tumor DNA, ctDNA). Various technologies are available that offer reliable detection of ctDNA at a low concentration. Quantitative and qualitative analys...

The Interferon (ΙFN) Type-I pathway has an important role in the activation of an anti-tumor immune response. We investigated the effects of two different dose fractionations of radiation (3 daily 8 Gy fractions vs. one fraction of 20 Gy) on the activation of the Type-I IFN-pathway in three hormone-dependent (22Rv1) and independent (DU145, PC3), pr...

Purpose: Non-small cell lung cancer (NSCLC) is one of the most lethal tumors in humans. Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced diseases. Tumor microenvironment conditions like hypoxia and low pH may compromise the efficacy of ICIs. Materials and methods: We report the eff...

PD-L1/PD-1 pathway is a major pathway exploited by human cancer types, which is a target for current immunotherapy. We investigated tumor microenvironmental factors involved in PD-L1 induction in prostate cancer (PC). We studied the expression of PD-L1 in a series of 66 PCs, in parallel with the expression of hypoxia- and acidity-related immunohist...

Introduction Patients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immu...

Simple Summary The presence of tumor-infiltrating lymphocytes (TILs) in the tumor milieu has been linked to better patient prognosis and response to chemo-radiotherapy in head and neck carcinoma, among other malignancies. We studied 60 cases of squamous cell carcinoma of the lip to assess the presence of TILs and their subpopulations and tertiary l...

Background The presence and activity of tumor-infiltrating lymphocytes (TILs) is a key parameter related to the antitumor immune response. A large number of studies reveal TIL density as a prognostic marker and predictor of response to radiotherapy, chemotherapy, and immunotherapy. Methods We examined the TIL and tertiary lymphoid structure TLS de...

We assessed the presence of 'tertiary lymphoid structures' (TLS) in a series of surgically treated non-small cell lung carcinomas (NSCLC). The TLS-density in the tumor periphery (pTLS) ranged from 0-1.8 (median 0.45), while in inner tumor areas (iTLS) ranged from 0-1.0 (median 0); (p < 0.0001). High pTLS-density was linked with early stage of the d...

Chemo-radiotherapy is the standard treatment for locally advanced head–neck cancer (LA-HNC). However, about 30% of tumors do not respond or even progress shortly after the completion of radiotherapy. We investigated whether anti-PD1 immunotherapy can eradicate the irradiated tumor and reverse the ominous prognosis of these patients. We retrospectiv...

Purpose Lung cancer is considered as one of the most frequent malignancies worldwide. Radiotherapy is the main treatment modality applied for locally advanced disease, but remnant surviving cancer tissue results in disease progression in the majority of irradiated lung carcinomas. Metabolic reprogramming is regarded as a cancer hallmark and is asso...

Purpose Hypoxia-Inducible Factor HIF1α and lactate dehydrogenase LDHA drive anaerobic tumor metabolism and define clinical aggressiveness. We investigated their expression in breast cancer and their role in immune response and prognosis of breast cancer. Methods Tissue material from 175 breast cancer patients treated in a prospective study were an...

Purpose: Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the...

Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head-neck tumors (HNSCC). Moreover, we assessed the link bet...

Background: Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRPα ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development. Methods: We investigated the expression of CD47/SIRPα molecules in a series of 98...

Purpose: Radiotherapy is a principal treatment modality for localized and locally advanced prostate cancer (PCa). Metabolic alterations, including lipid metabolism, may reduce treatment efficacy resulting in tumor relapse and poor therapeutic outcome. In the current study, we investigated the role of the lipophagy-related protein perilipin-3 (PLIN3...

Cancer immuno-editing frequently leads to loss of HLA-class-I molecule (HLA) expression and impaired immune surveillance. We investigated the expression of HLAs in a series of operable non-small-cell lung carcinomas (NSCLCs). Complete loss and extensive loss of expression was noted in 41.5% and 23.4% of cases, respectively. Low CD8+ and FOXP3+ TIL-...

The tumor-draining lymph nodes (TDLNs) are the primary sites of the development of anti-tumor immunity. Primary tumor irradiation promotes ‘radio-vaccination’ by enhancing the release of tumor antigens and activating the interferon type-I pathway. Activated intratumoral dendritic cells (DCs) enter the lymphatics to reach the TDLNs. The adaptive ant...

Background/aim: Aldehyde dehydrogenases (ALDHs) are considered as markers for normal and cancer stem cells (CSC) and are involved in cell metabolism, proliferation, differentiation, stemness, and retinoic acid (RA) biosynthesis. The aim of the present study was to identify the ALDH isoforms that are associated with the CSC phenotype in non-small c...

Lipid metabolism reprogramming is one of the adaptive events that drive tumor development and survival, and may account for resistance to chemotherapeutic drugs. Perilipins are structural proteins associated with lipophagy and lipid droplet integrity, and their overexpression is associated with tumor aggressiveness. Here, we sought to explore the r...

Since its first clinical application, 120 years ago, radiotherapy evolved into a major anti-cancer treatment modality, offering high cure rates in many human malignancies. During the past ten years, the establishment of immune checkpoint inhibitors (ICIs) in cancer therapeutics has vigorously reintroduced the immune system’s role in the outcome of...

We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×1...

The combination of radiotherapy with bicalutamide is the standard treatment of prostate cancer patients with high-risk or locally advanced disease. Whether new-generation anti-androgens, like apalutamide, can improve the radio-curability of these patients is an emerging challenge. We comparatively examined the radio-sensitising activity of apalutam...

Background Arginine (Arg) is essential for cancer cell growth and also for the activation of T cells. Thus, therapies aiming to reduce Arg utilization by cancer may prove detrimental for the immune response. Methods We examined the expression of two major enzymes involved in arginine depletion and replenishment, namely arginase ARG2 and argininosu...

Background/aim: Non-small cell lung cancer (NSCLC) is one of the most lethal tumors. Given the failure of conventional therapeutic strategies, immunotherapy has emerged as a promising treatment modality that may improve the survival of patients with operable and advanced disease. Patients and methods: We examined the relative presence of CD20+ B...

Introduction: Adult medulloblastoma is a rare disease. Due to the length of the body areas demanding irradiation, medulloblastoma is a challenging malignancy for the development of advanced radiotherapy techniques. Case Report: We describe a volumetric modulated arc therapy (VMAT) technique applied under image-guided radiation therapy (IGRT) for cr...

Phyllodes tumors are rare breast lesions of fibroepithelial origin. Malignant transformation with metastases is linked with poor prognosis. We present a case of a 62-year-old woman with a recurrent malignant phyllodes tumor of the breast and lung metastases. The patient was originally presented with a borderline phyllodes tumor (7.4 cm) of the left...

Introduction Angiogenic activity and vascular survival ability are two distinct vasculature related tumor features that can be assessed in tumor tissues. We examined their correlation with anti-tumor immunity in a series of endometrial carcinomas. Material and Methods Thirty-three, stage I, endometrial carcinomas of endometrioid histology were ana...

Objective Radiotherapy provides excellent results in locally advanced cutaneous squamous-cell carcinoma of the head and neck area (cSCC-HN), with a 2-year local progression-free interval obtained for about 80% of patients. Overexpression of immune checkpoint co-inhibitory molecules, like PD-L1 (programmed death ligand 1), by cancer cells may define...

Introduction The immune response has been recognized as a major tumor-eradication component of radiotherapy. Objective This review studies, under a clinical perspective, two contrasting effects of radiotherapy, namely immunosuppression and radiovaccination. Materials and methods We critically reviewed the available clinical and experimental exper...

Background/aim: Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. Patients and methods: We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different H...

Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. ALDHs participate in a variety of cellular mechanisms, such as metabolism, cell proliferation and apoptosis, as well as differentiation and stemness. Over the last few years, ALDHs...

Tumor-draining lymph nodes (TDLNs) are critical organs, where activation of B cells and T cells is orchestrated. Effector or regulatory anti-tumor immune responses are reflected by the composition of the lymphocytic and monocytic cell population of the node. Aside from the migratory cancer cell abilities, immune cell phenotypic changes in the TDLNs...

Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia...

Background/aim: The role of senescence in defining tumor aggressiveness at a clinical level remains obscure. A novel mixed histochemical/immunohistochemical method (SenTraGor™, STG) detecting lipofuscin accumulation allows the assessment of senescent cells in paraffin-embedded tissue material. Materials and methods: STG expression was quantified...

Aims: Adenosine triphosphate (ATP) is released at a high concentration in the tumor microenvironment. The overexpression of ectonucleotidases in non-small-cell lung cancer (NSCLC), metabolizing ΑΤP to the immunosuppressive adenosine, is studied. Materials and methods: We examined the expression of the ectonucleotidases CD73 and CD39 in NSCLC in...

The radio-immunization effects of radiotherapy with abscopal tumor regressions have been documented in several experimental and clinical studies. Here, we present a patient with bladder cancer and relapsed metastatic disease to the left supraclavicular/axillary area and left lung. Concurrent weekly hypofractionated radiotherapy of both areas (8Gy/f...

Low pH suppresses the proliferation and cytotoxic activity of CD8+ cytotoxic and natural killer lymphocytes. The hypoxia-regulated transmembrane protein, carbonic anhydrase CA9, converts carbon dioxide produced by the Krebs cycle to bicarbonate and protons that acidify the extracellular milieu. We examined whether CA9 is also involved in intratumou...

Introduction: Senescent cells in tumors are not inert cells but exert bystander effects by developing secretory phenotypes affecting the extracellular matrix and interfering the biological behavior of adjacent tumor cells. Materials and methods: We assessed putative senescent cell content in a series of human sarcomas, using in parallel markers...

Background: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa). Objectives: To investigate the role of CYP17A1 as a driver of PCa growth. Materials and methods: We examined the expression of CYP17A1 and of androgen receptors (AR) in PC...

Background/aim: Uterine sarcoma is an aggressive tumor associated with poor survival, compared to endometrioid carcinoma. Postoperative local radiotherapy and chemotherapy are controversial. Patients and methods: We report a retrospective analysis of 14 patients with uterine homologous type carcinosarcoma (9 patients) or leiomyosarcoma (5 patien...

The microenvironment of a tumor may regulate the anti-tumor immune response. Intratumoral acidosis and hypoxia may suppress lymphocyte proliferation and migration, and this may have important implications in modern immunotherapy. The expression of PD-L1 by cancer cells and of PD-1 by tumor infiltrating lymphocytes (TILs) was assessed in tissue spec...

Aims: Lung cancer is one of the main causes of cancer-related deaths worldwide and radiotherapy is a major treatment of choice. However, radioresistance is a main reason for radiotherapy failure or tumor relapse. Here, we investigated possible mechanisms associated with cancer cell radioresistance. Materials and methods: We compared two newly de...

Purpose/Aim: Regulatory FOXP3+ T-cells control the cytotoxic activity of effector cells and may have an essential role in the development of immune tolerance in cancer patients. Programed death ligand 1 PD-L1, expressed on cancer cell membranes also blocks the cytotoxic activity of PD1+ cytotoxic lymphocytes. Materials and Methods: We assessed the...

Previous studies from our group have brought forward the concept of angiogenic regeneration during radiotherapy (RT), as a major cause of RT failure. This process was examined herein in rectal cancer patients undergoing preoperative chemo-radiotherapy. Out of 25 patients with stage II/III rectal adenocarcinoma, 15 had incomplete response (pIR) afte...

Background: The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer. Materials and Methods: Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-asso...

Effective cytoprotectors that are selective for normal tissues could decrease radiotherapy and chemotherapy sequelae and facilitate the safe administration of higher radiation doses. This could improve the cure rates of radiotherapy for cancer patients. Autophagy is a cytoplasmic cellular process that is necessary for the clearance of damaged or ag...

Background: Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies. Materials and methods: Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carc...

Purpose: The anaerobic metabolism of glucose by cancer cells, even under well oxygenated conditions, has been documented by Otto Warburg as early as 1927. Micro-environmental hypoxia and intracellular pathways activating the hypoxia-related gene response, shift cancer cell metabolism to anaerobic pathways. In the current review we focus on a major...

Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and bicalutamide on the expression c...

Background/aim: We investigated the expression of angiogenesis and hypoxia markers in the adenohypophysis and neurohypophysis of patients who died from various acute or chronic diseases. Materials and methods: Paraffin-embedded material of pituitary glands (97 patients) was investigated immunohistochemically for vascular density (CD31) and the e...

Background/aim: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. Materials and methods: We investigated the effect of amifostine on autophagy, lysosomal bioge...

Objective: : Cancer cell radioresistance is a stumbling block in radiation therapy. The activity in the nuclear factor kappa B (NFκB) pathway correlates with anti-apoptotic mechanisms and increased radioresistance. The IKK complex plays a major role in NFκB activation upon numerous signals. In this study, we examined the interaction between ionizi...

Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of...

Purpose: Up-regulation of lactate dehydrogenase LDHA, is a frequent event in human malignancies and relate to poor postoperative outcome. In the current study we examined the hypothesis that LDHA and anaerobic glycolysis, may contribute to the resistance of glioblastoma to radiotherapy and to temozolomide. Methods and materials: The expression o...

Materials and methods: We investigated the expression and prognostic relevance of enzymes involved in the glucose absorption and metabolism, monocarboxylate transporter (MCT) expression, MCT1 and MCT2, pentose pathway (Glucose-6-phospahte dehydrogenase G6PD), glycogene synthesis (glycogene synthase GYS1), glycolysis (Hexokinase HXKII, phosphofruct...

Background/Aim: Altered fractionation is an area of intense clinical research in radiation oncology. Estimation of the α/β ratio of individual carcinomas after establishment of primary cell cultures from tumor biopsies may prove of importance in the individualization of radiotherapy schemes. Materials and Methods: Here we proposed a simple method t...

Micro-RNAs (miRNAs) have a complex role in carcinogenesis and tumour progression. Several miRNAs, such as miR-221, miR-27b and miR-132, have been implicated in the regulation of VEGF tumour angiogenic activity. In this pilot study, we assessed angiogenesis and DLL4+ vascular maturation index (VMI) in breast cancer tissues, in parallel with the plas...

The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished via direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a D-ribose derived chiron. Naturally occurring trachycladines (A and B) and a series of analogues were examined for their cytotoxic activity against a...

This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA an...

Background: Disrupting the autophagic balance to trigger autophagic death may open new strategies for cancer therapy. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and may play a role in cancer biology and clinical behavior. Methods: The expression of TFEB and the lysosomal cancer cell content (expression of lysoso...

The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients...

Background The cellular autophagic response to radiation is complex. Various cells and tissues respond differentially to radiation, depending on both the dose of exposure and the time post irradiation. In the current study, we determined the autophagosomal and lysosomal response to radiation in lung cancer cell lines by evaluating the expression of...

Aldehyde dehydrogenases participate in a variety of cellular homeostatic mechanisms like metabolism, proliferation, differentiation, apoptosis, whereas recently, they have been implicated in normal and cancer cell stemness. We explored roles for ALDH3A1 in conferring resistance to chemotherapeutics/radiation/oxidative stress and whether ectopic ove...

Purpose In vivo radiobiology experiments involving partial body irradiation (PBI) of mice are of major importance because they allow for the evaluation of individual organ tolerance; overcoming current limitations of experiments using lower dose, whole body irradiation. In the current study, the authors characterize and validate an effective and ef...

Purpose: To assess whether anaerobic metabolism, proliferation activity and stem cell content are linked with radioresistance in bladder cancer. Materials and methods: Tissue sections from 66 patients with invasive transitional cell bladder cancer treated with hypofractionated accelerated radiotherapy, was immunohistochemically analyzed for the...

Glioblastoma is a unique model of non-metastasising disease that kills the vast majority of patients through local growth, despite surgery and local irradiation. Glioblastoma cells are resistant to apoptotic stimuli, and their death occurs through autophagy. This review aims to critically present our knowledge regarding the autophagic response of g...

Lung cancer is responsible for most fatalities amongst cancers worldwide. Within the frames of the Metaboli-Ca project, in order to gain deeper insight regarding the molecular crosstalk taking place between the tumor cells and the surrounding stroma, we analyze with the help of next generation sequencing (NGS) techniques, specimens from lung sectio...

Background: The aim of this study was to investigate whether electrochemotherapy is a clinically and cost-effective treatment option against skin tumors. Materials and methods: We performed an analysis of the current literature based on database searches in PubMed/MEDLINE and we included articles till July 2012. Terms used for the search were 'e...

LC3s (MAP1-LC3A, B and C) are structural proteins of autophagosomal membranes, widely used as biomarkers of autophagy. Whether these three LC3 proteins have a similar biological role in autophagy remains obscure. We examine in parallel the subcellular expression patterns of the three LC3 proteins in a panel of human cancer cell lines, as well as in...

The microtubule-associated protein light chain 3 MAP1LC3 (LC3) and GABARAPL1 and 2 are the major proteins to monitor autophagy. Here, we analyzed the role of both MAP1LC3, GABARAPL1 and 2 in breast cancer cells and primary human breast cancer. HER2 amplified (BT474, SKBR3, MDA-MB-453), ER positive (MCF7, T47D) and triple negative (MDAMB231) breast...

MicroRNAs (miRNAs) are small stable endogenous RNAs, found in all complex organisms and considered by nature as inhibitors of mRNA translation. This class of small posttranscriptional regulatory RNAs originates from the random formation of hairpin precursors in "non-coding" DNA regions; their main function is the control of gene expression status....

Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy....

Radiotherapy is an equivalent alternative or complement to radical prostatectomy, with high therapeutic efficacy. High risk patients, however, experience high relapse rates, so that research on radio-sensitization is the most evident route to improve curability of this common disease. In the current study we investigated the autophagic activity in...

The current study examines the effect of fever-range hyperthermia and mild hypothermia on human cancer cells focusing on cell viability, proliferation and HSP90 expression. A549 and H1299 lung carcinoma, MCF7 breast adenocarcinoma, U87MG and T98G glioblastoma, DU145 and PC3 prostate carcinoma and MRC5 normal fetal lung fibroblasts cell lines were s...

ABSTRACT Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series...

Abnormal mitochondrial function is common in cancer cells and activates metabolic pathways suppressed in normal tissues. Experimental and clinical studies suggest that mitochondria might serve as targets for novel anticancer therapies. We investigated whether mitochondrial metabolism-interfering agents (MMIAs) available currently in clinical practi...

Objectives Vasculature damage is an important contributor to the side-effects of radiotherapy. The aim of this study is to provide insights into the radiobiology of the autophagic response of endothelial cells. Methods and Materials Human umbilical vascular endothelial cells (HUVEC) were exposed to 2 Gy of ionizing radiation (IR) and studied using...

Background: Radiotherapy for lung cancer may induce pneumonitis. However, histological effects of radiotherapy on normal lung tissue are unknown. Transbronchial biopsy (TBB) is safe and accurate in monitoring parenchymal lesions in lung-transplanted patients. The aim of this prospective study was to evaluate whether histological changes of the hea...

Mitochondria and cell metabolism play a crucial role on cell survival and constitute potential target in order to obtain deeper knowledge about cancer. This current study had focused on how metabolism interfering agents affect on metabolism of resazurin in mitochondria and if these drugs could sensitize the cells to chemotherapy. A549 (lung cancer...

Glioblastoma is the most aggressive tumor of central nervous system. Aytophagy is an intracellular pathway that aims at recycling of damaged proteins and organelles via a process of engulfing them in autophagosomes and fusing with lysosomes. The basic proteins that take part in this pathway is LC3A and LC3B (aytophagosomes’ proteins), Lamp2a (lysos...

Glioblastoma is the most aggressive tumor of central nervous system. Aytophagy is an intracellular pathway that aims at recycling of damaged proteins and organelles via a process of engulfing them in autophagosomes and fusing with lysosomes. The basic proteins that take part in this pathway is LC3A and LC3B (aytophagosomes’ proteins), Lamp2a (lysos...

Delta-like ligand 4 (DLL4) is a ligand of the notch pathway. In tumor angiogenesis, DLL4 switches to vascular maturation by providing a negative feedback on VEGFR2 activity. We investigated the expression of DLL4 in the plasma and cancer tissues from breast cancer patients. Plasma samples were collected from 18 women with localized breast cancer, s...

Abstract Ionizing radiation cause DNA damage to cells, leading them to cell death via DNA double-strand breaks (DSBs) formation. DSBs formation is followed immediately by histone H2AX phosphorylation (γ-H2AX) and multitude repair factors accumulation. Here we present the methods and the bio-sampling for γ-H2AX detection, γ-H2AX formation in normal...