Konstantinos Dimas

• Professor (Assistant) at University of Thessaly

Background/Objectives: Cancer is a dynamic and complex disease that remains largely untreated despite major advances in oncology and treatment. In this context, we aimed here to investigate optimal control techniques in the management of tumor growth inhibition, with a particular focus on cancer chemotherapy treatment strategies. Methods: Using bot...

Graphene is a material, which has attracted great attention of the scientific community in several fields of biomedicine, neurosciences being one of the fields holding great interest for the application of graphene-based materials and devices. Our study aimed to determine the in vivo brain tissue reaction and to study the possible impairment of mem...

Background/Aim: Despite the advances in oncology and cancer treatment over the past decades, cancer remains one of the deadliest diseases. This study focuses on further understanding the complex nature of cancer by using mathematical tumor modeling to understand, capture as best as possible, and describe its complex dynamics under chemotherapy trea...

Background and Objectives: Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum gemcitabine levels and use it in pharmacokinetic studies. Materials and Methods: The analysis was performed after a single protein precipitation step on a r...

Background/aim Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and l...

Background Gastrointestinal (GI) cancers remain a major threat worldwide, accounting for over 30% of cancer deaths. The identification of novel prognostic biomarkers remains a challenge despite significant advances in the field. The CAV1 gene, encoding the caveolin‐1 protein, remains enigmatic in cancer and carcinogenesis, as it has been proposed t...

Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with remarkable resistance to treatment, poor prognosis, and poor clinical outcome. More efficient therapeutic approaches are urgently needed to improve patients’ survival. Recently, the development of organoid culture syste...

The 90 kDa ribosomal S6 kinase (RSK) family of proteins is a group of highly conserved Ser/Thr kinases. They are downstream effectors of the Ras/ERK/MAPK signaling cascade. ERK1/2 activation directly results in the phosphorylation of RSKs, which further, through interaction with a variety of different downstream substrates, activate various signali...

Τhe synthesis of a series of novel hybrid block copolypeptides based on poly(ethylene oxide) (PEO), poly(l-histidine) (PHis) and poly(l-cysteine) (PCys) is presented. The synthesis of the terpolymers was achieved through a ring-opening polymerization (ROP) of the corresponding protected N-carboxy anhydrides of Nim-Trityl-l-histidine and S-tert-buty...

Mitochondria are important organelles for cellular physiology as they generate most of the energy requirements of the cell and orchestrate many biological functions. Dysregulation of mitochondrial function is associated with many pathological conditions, including cancer development. Mitochondrial glucocorticoid receptor (mtGR) is proposed as a cru...

Immunotherapy has emerged as a viable approach in cancer therapy, with cytokines being of great interest. Interleukin IL-15 (IL-15), a cytokine that supports cytotoxic immune cells, has been successfully tested as an anti-cancer and anti-metastatic agent, but combinations with conventional chemotherapy and surgery protocols have not been extensivel...

Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis of PDAC. Materials and Methods:...

Introduction: Metastasis is responsible for most of the cancer-related deaths (~ 90%). Metastatic triple negative breast cancer (TNBC) has poor survival and chemotherapy pre- and post-surgery has been the standard treatment for decades. Polymorphonuclear - myeloid derived suppressor cells (PMN-MDSCs) are implicated in the process of metastasis. IL-...

Background/aim: Pancreatic cancer (PC) is one of the leading causes of cancer-related death. The purpose of the present study was to establish a patient-derived orthotopic xenograft model (PDOX) for pancreatic ductal adenocarcinoma (PDAC), thus providing a tumor microenvironment resembling that of the human pancreas to identify novel potential bio...

Research on the improvement and fabrication of polymeric systems as non-viral gene delivery carriers is required for their implementation in gene therapy. Random copolymers have not been extensively utilized for these purposes. In this regard, double hydrophilic poly[(2-(dimethylamino) ethyl methacrylate)-co-(oligo(ethylene glycol) methyl ether met...

Combined use of a chemotherapeutic agent and an autophagy inhibitor is a novel cancer treatment strategy. We investigated the effects of chloroquine (CQ) on lung pathology caused by both solid Ehrlich ascites carcinoma (EAC) and doxorubicin (DXR). A control group and eight experimental groups of adult female mice were inoculated subcutaneously with...

The crosstalk between the exercising muscle and the adipose tissue, mediated by myokines and metabolites, derived from both tissues during exercise has created a controversy between animal and human studies with respect to the impact of exercise on the browning process. The aim of this study was to investigate whether co-culturing of C2C12 myotubes...

Caveolin-1 (CAV1) is expressed in several solid tumors both in cancerous cells as well as in tumor stroma and is reported to be related to cancer progression, metastasis, therapy resistance and clinical outcomes. Many studies report contrasting functions of this protein depending on the tumor cell model, the tumor type, or the stage of cancer studi...

Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs [...]

Tumor chemosensitivity assays (TCAs), also known as drug response assays or individualized tumor response tests, have been gaining attention over the past few decades. Although there have been strong positive correlations between the results of these assays and clinical outcomes, they are still not considered routine tests in the care of cancer pat...

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to effi...

mTORC2 promotes cell survival by phosphorylating AKT and enhancing its activity. Inactivation of mTORC2 reduces viability through down-regulation of E2F1 caused by up-regulation of c-MYC. An additional target of mTORC2 is IGF2BP1, an oncofetal RNA binding protein expressed de novo in a wide array of malignancies. IGF2BP1 enhances c-MYC expression b...

Resveratrol is a polyphenolic compound which is found in many nutrients including grapes, peanuts, raspberries, and apples. Anti-proliferative, anti-angiogenic and apoptotic effects of resveratrol have been shown on various cancer cells. Doxorubicin is considered as one of the most effective anticancer agents and reveals its antitumor activity by i...

Sigma (σ) receptors have attracted great interest since they are implicated in various cellular functions and biological processes and diseases, including various types of cancer. The receptor family consists of two subtypes: sigma-1 (σ1) and sigma-2 (σ2). Both σ receptor subtypes have been proposed as therapeutic targets for various types of cance...

Cancer is the second leading cause of death globally with an estimated 9.6 million deaths in 2018 and a sustained rise in its incidence in both developing and developed countries. According to the WHO, about 1 in 6 deaths is due to cancer. Despite the emergence of many pioneer therapeutic options for patients with cancer, their efficacy is still ti...

BACKGROUND The European Union Directives stipulate mandatory tests for the presence of some infections in donors or donations of substances of human origin (SoHO). In some circumstances, other pathogens including fungi and parasites may also pose a threat to the microbial safety of SoHO. OBJECTIVE The aim of the two systematic reviews is to identi...

Background The European Union Directives stipulate mandatory tests for the presence of any infections in donors and donations of substances of human origin (SoHO). In some circumstances, other pathogens, including fungi and parasites, may also pose a threat to the microbial safety of SoHO. Objective The aim of the two systematic reviews is to ident...

Aim: Mathematical models are considered important tools in studying and understanding cancer biology and in the improvement of anticancer therapies. Herein, we present an advanced non-linear mathematical model that can predict accurately the effect of an anticancer agent on the growth of a solid tumor. Materials and methods: Advanced non-linear mat...

Background/aim: Mathematical models have long been considered as important tools in cancer biology and therapy. Herein, we present an advanced non-linear mathematical model that can predict accurately the effect of an anticancer agent on the growth of a solid tumor. Materials and methods: Advanced non-linear mathematical optimization techniques...

Introduction: We evaluated the potential therapeutic benefit of conventional chemotherapy combined with hetIL-15 immunotherapy in two mouse models of pancreatic and breast cancer. IL-15 is an important cytokine that stimulates the proliferation and cytotoxic functions of CD8⁺ T cells and NK cells. We have produced the native heterodimeric form of I...

Background hetIL-15 is evaluated in on-going immunotherapy clinical trials. We studied the mechanism of hetIL-15 antitumor function in several mouse models (MC38, TC-1, 4T1 and EO771). Methods We evaluated tumor immune infiltrate by flow cytometry, multi-color immunohistochemistry (IHC), transcriptomics and proteomics. Results hetIL-15 treatment...

Background Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial. Objectives The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CL...

Purpose: Growth factors such as fibroblast growth factor 2 (FGF-2) and hepatocyte growth factor (HGF) appear at high levels in prostate cancer (PC). Abiraterone is an androgen biosynthesis inhibitor which is currently in use as a standard treatment in clinics to impair tumor growth. Development of resistance to anticancer therapies is unfortunatel...

The aim of this study was to investigate the effects of inhibition of Notch, IL‐1 and leptin systems on tumorigenesis and angiogenesis in xenograft colorectal cancer model. This study was conducted with the approval of the EU/2010/63 directive and the Greek Presidential Decree 56/2013 (Approval No. 5542/228006/1). In each group, 40 scid (NOD/SCID)...

Background: This study aimed to assess the differential gene expression of aquaporin (AQP) gene family interactome in pancreatic ductal adenocarcinoma (PDAC) using data mining techniques to identify novel candidate genes intervening in the pathogenicity of PDAC. Method: Transcriptome data mining techniques were used in order to construct the int...

Caveolin‑1 (Cav‑1) expression has been shown to be associated with tumor growth and resistance to chemotherapy in pancreatic cancer. The primary aim of this study was to explore the significance of Cav‑1 expression in pancreatic cancer cells as compared to fibroblasts in relation to cancer cell proliferation and chemoresistance, both in vitro and i...

A novel, multifunctional hydrogel that exhibits a unique set of properties for the effective treatment of pancreatic cancer (PC) is presented. The material is comprised of a pentablock terpolypeptide of the type PLys-b-(PHIS-co-PBLG)-PLys-b-(PHIS-co-PBLG)-b-PLys which is a non-cytotoxic polymer. It can be implanted via the least invasive route and...

Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. Materials and methods: The cytotoxic effect of doxorubicin (0.1-1 μM), chloroquine (0.25-32 μM) and their combination were investigated by employing ATP assay...

In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and seeds) been reported having antica...

Introduction: In this preclinical study, we tried to model the therapeutic strategies often used in the clinic to treat breast cancer patients. We analyzed the role of hetIL 15 immunotherapy alone and in combination with chemotherapy and surgery using the 4T1, a triple-negative breast cancer cell line, murine breast cancer model. Experimental Proce...

Introduction Pancreatic cancer is a highly malignant tumour, poorly responsive to conventional therapies that result in a progressive resistance to treatment. Sigma receptors (sigma-1 and sigma-2) are widespread in central nervous system and multiple peripheral tissues. Selective sigma ligands (agonists and antagonists) label tumour sites, induce a...

Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To ass...

Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injurie...

The prognosis of pancreatic ductal adenocarcinoma (PDAC), the eighth most lethal cancer for men and ninth for women worldwide, remains dismal. The increasing rates of deaths by PDAC indicate that the overall management of the disease in 21st century is still insufficient. Thus it is obvious that there is an unmet need to improve management of PDAC...

The invention relates to the methods for synthesis, chemical structure and in vivo and in vitro anticancer effects of a palladium complex ([Pd(bpma)(barb)|X.H2O]) with high anticancer activity.

Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downre...

Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth acti...

The exploration of natural products is of importance because the management of cancer is still not satisfactory. Pristimerin is a naturally occurring triterpenoid that has been shown to suppress the proliferation of various cancer cell lines at relatively lower concentrations, of which the IC50 values are around 0.5–4 μM. Its cytotoxic potential on...

Background/aims: Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis...

Background/aim: Medulloblastoma (MBL), an archetypal primitive neuroectodermal tumor of the cerebellum, is the most common pediatric central nervous system malignancy representing approximately 20% of all childhood brain tumors. Herein, we report on a new xenotransplantable tumor cell line, derived from a 6-year-old female patient with cerebellar...

Buluş yüksek antikanser etki gösteren bir palladyum kompleksinin ([Pd(bpma)(barb)]X.H2O) sentez yöntemi, kimyasal yapı ve in vitro ve in vivo anti kanser etkisiyle ilgilidir.

Aptamer Drug Conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells, whilst sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic...

There has been an enormous interest in the literature that phyto-compounds have therapeutic and beneficial effects in various diseases including inflammatory associated arthritis, diabetes, hypertension, parasitic infections, and cancer. A natural extract isolated from the leafs and the root of the Chinese herb Tripterygium wilfordii Hook “F” shown...

Phyto-compounds are beneficial in healthcare sector that have contributed in many aspects in Medicine. Studies have demonstrated the progressive effects of phyto-compounds on immune related diseases, quality of life of cancer patients. Graviola is a tree where its extracts (leafs, seeds) are known to be beneficial against cancer. Graviola has been...

Natural plant extracts have been used for centuries for treating many types of diseases Including inflammatory related diseases as well as cancer. One of these extracts is amygdalin which is a natural compound mostly extracted from the seeds of bitter almonds and apricots. Due to its cyanate containing structure, amygdalin has been reported to have...

PurposeBortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. MethodsNCI-H929 and RPMI-8226 (human MM cell lines) were...

Interleukin-15 (IL-15) is a common γ-chain cytokine that plays a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha chain that are tog...

Despite significant advances in the management of colorectal cancer the identification of new prognostic biomarkers continues to be a challenge. Since its initial discovery, the role of the Hedgehog (Hh) signaling pathway in carcinogenesis has been extensively studied. We herein review and comment on the prognostic significance of the Hedgehog sign...

Gestational choriocarcinoma is a type of gestational trophoblastic cancer. It is associated with the reproductive system can be aggressive invading and metastasizing mainly to lungs, but is also highly responsive to chemotherapy. It is very rare, approximately 1:50,000 for normal pregnancies. It most often occurs after a complete hydatidiform mole....

Kaposi's sarcoma is a type of cancer caused by Kaposi's sarcoma-associated herpes virus (KSHV), a member of the family herpesviruses (or herpesviridae) and one of the nine known oncoviruses. Herpes viruses are widely disseminated in the animal kingdom. Symptoms of these infections were noted by the ancient Greeks, which led to the name herpes for t...

Context • Turmeric (Curcuma longa) is a food spice and colorant reported to be beneficial for human health. Curcumin (diferuloylmethane) is the major ingredient in turmeric, and existing data suggest that the spice, in combination with chemotherapy, provides a superior strategy for treatment of gastrointestinal cancer. However, despite its signific...

Mammalian target of rapamycin (mTOR) forms 2 active complexes in the cell: the rapamycin-sensitive mTOR-Raptor (mTORC1) and the rapamycin-insensitive mTOR-Rictor (mTORC2). The latter activates AKT kinase, which promotes tumor cell survival and proliferation by multiple downstream targets. Mammalian stress-activated protein kinase interacting protei...

Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for the treatment of various cardiac conditions. Recent published data with Na+/K+ ATPase inhibitors suggest a potent anti-cancer action of these agents in multiple indications. In the present study, we focus on istaroxime, a Na+/K+ ATPase inhibitor that has shown favorable...

Well-defined amphiphilic polymers of the ABA and ABC type are synthesized, where A is poly(L-lysine hydrochloride) (PLL), B is poly(γ-benzyl-(d7) L-glutamate) (PBLG(-d7)), and C is poly(ethylene oxide) (PEO). The two polymers exhibit similar PBLG(-d7) composition, while in the ABC, the volume fraction of PEO block is higher than that of PLL. Both p...

Recently we have reported potent anti-cancer actions of various steroidal Na+/K+ ATPase inhibitors in multiple cell lines. Furthermore, the most powerful compound identified in this study, the 3-[(R)-3-pyrrolidinyl]oxime derivative (3-R-POD), was highly effective in various tumor cell lines in vitro, and exhibited significant tumor growth inhibitio...

Eye cancer is rare as its occurrence is lower than other types of cancer. The most common types are intraocular melanoma for the adults and retinoblastoma for the children. As with other cancers, there are both environmental and genetic determinants in the development of eye cancer. Secondary cancers may also appear in the eye. In women this is mos...

Salivary gland cancer is a type of head and neck cancer. Salivary gland tumors represent a diverse group of neoplasms. They are uncommon lesions that are distinct from other cancers of the head and neck and account for approximately 6% of neoplasms in that anatomic region. It is generally believed that alterations within stem or reserve (basal) cel...

Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for the treatment of congestive heart failure. Recent data with inotropic drugs such as digoxin & digitoxin (digitalis) suggest a potent anti-cancer action of these drugs and promote Na+/K+ ATPase as a novel therapeutic target in cancer. However, digitalis have narrow thera...

Dendrimers are important molecules that are currently undergoing investigation for use in a variety of different biomedical applications. This book explores the use of dendrimers for a variety of potential functions, including antiamyloidogenic agents, drug delivery systems, nucleic acid and RNA delivery vectors and to produce hybrid fibre platform...

The combination of natural and synthetic biomaterials leads to the formation of advanced Drug Delivery nano Systems (aDDnSs). The aDDnSs can be classified as hybridic (hy‐) or chimeric (chi‐) based on the nature – same or different respectively ‐ of biomaterials used. Such advanced bio complexes can alter the pharmacokinetic properties of the encap...

e16083 Background: In the prostatic epithelium endothelin-1 (ET-1), fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell proliferation and inhibition of apoptosis. The aim of this study is to investigate whether neuropeptides such as ET-1 and growth factors such as FGF and HGF may constitute an alternate pathway...

Abstract 9-Substituted (pyrazol-5-yl)methyl- or (2-pyrazolin-5-yl)methyl-9H-purines were synthesized from 9-allyl-6-chloro-9H-purine through the 1,3-dipolar cycloaddition reaction with nitrile imines, prepared in situ from the corresponding hydrazone and NBS/Et(3)N under MW or from hydrazinoylchloride and Et(3)N under reflux. The coupling of new 6-...

Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for the treatment of congestive heart failure. Recent data with inotropic drugs such as digoxin & digitoxin (digitalis) suggest a potent anti-cancer action of these drugs and promote Na+/K+ ATPase as a novel therapeutic target in cancer. However, digitalis have narrow thera...

The synthesis of the adamantane phenylalkylamines 2a-d, 3a-c and 4a-e is described. These compounds exhibited significant antiproliferative activity, in vitro, against eight cancer cell lines tested. The sigma-1 (σ1), sigma-2 (σ2) and sodium channels binding affinities of the compounds 2a, 3a, 4a and 4c-e were investigated. One more interesting ana...

Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var. chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO consist of nearly 70 constituents and have demonstrated numerous and diverse biomedical and pharmacological properties including (a) eradication of bacteria and fungi that may cause peptic ulce...