Stamatios Theocharis

National and Kapodistrian University of Athens | uoa · Division of Internal Medicine I

Endometriosis constitutes the most common cause of chronic pelvic pain in female patients and is associated with infertility. Although there is no known cause for the disease, it is a heritable condition that is determined by numerous genetic, epigenetic, and environmental aspects. Peroxisome proliferator-activated receptors (PPARs) represent nucle...

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin’s influence on EC. This review comprehensively elucidates th...

Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflam...

Hepatocellular carcinoma (HCC) remains a global health challenge with limited treatment options and a poor prognosis for advanced-stage patients. Recent advancements in cancer immunotherapy have generated significant interest in exploring novel approaches to combat HCC. One such approach involves the unique and versatile subset of T cells known as...

Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This subset of cancer cells with stemness and tumorigenic properties is organized in niches within the tumor microenvironment (TME) and presents altered regulation in a variety of metaboli...

Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still contro...

Simple Summary DAXX and HJURP are two proteins implicated in many physiologic processes and are considered important players contributing to the pathogenesis of a multitude of tumors. The aim of the present review of the literature is to retrieve and concisely present the data from studies conducted on human tissues that explored the expression of...

Citation: Papadakos, S.P.; Arvanitakis, K.; Stergiou, I.E.; Vallilas, C.; Sougioultzis, S.; Germanidis, G.; Theocharis, S. Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics. Pharmaceutics 2023, 15, 2460. https://doi. Abstract: Hepatocellular carcinoma (HCC) stands as a significant co...

Salivary gland tumors (SGTs) are rare and complex neoplasms characterized by heterogenous histology and clinical behavior as well as resistance to systemic therapy. Tumor etiology is currently under elucidation and an interplay of genetic and epigenetic changes has been proposed to contribute to tumor development. In this work, we investigated epig...

The escalating global prevalence of obesity and its intricate association with the development of hepatocellular carcinoma (HCC) pose a substantial challenge to public health. Obesity, acknowledged as a pervasive epidemic, is linked to an array of chronic diseases, including HCC, cat-alyzing the need for a comprehensive understanding of its molecul...

Introduction: Adenoid cystic carcinoma (AdCC) is typically indolent, however tends to behave more aggressively and present with perineural invasion and distant metastasis. Despite an improved understanding of AdCC pathobiology, the impact of anatomic tumor subsite (e.g., major versus minor salivary glands) on survival and response to treatment is r...

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate and limited treatment options. Recent research has brought attention to the significant importance of intercellular communication in the progression of HCC, wherein exosomes have been identified as critical agents facilitating cell-to-cell signaling. In this article...

Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomar...

Simple Summary The EPH/ephrin signaling axis holds a pivotal role in a plethora of physiologic processes during embryonic development and adult life, while more recent studies highlight its implication in the pathogenesis of multiple types of solid tumors. Different patterns of EPH/ephrin expression have been identified in normal hematopoiesis conc...

Given the pivotal role of the Hippo pathway in different facets of tumorigenesis, which has been vigorously established in multiple heterogenous malignancies, we attempted to evaluate its potential utility as a prognostic–predictive biomarker in thymic epithelial tumors (TETs). For this purpose, we performed a comprehensive immunohistochemical anal...

Simple Summary This narrative literature review delves into the role of EPH/ephrin signaling in liver cancer and its implications for tumor progression and potential therapeutic strategies. This review focuses on the relationship between hypoxia and HCC development, highlighting the upregulation of hypoxia-inducible factor 1-alpha (HIF-1α) in HCC c...

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. There has been significant progress in understanding the risk factors and epidemiology of HCC during the last few decades, resulting in efficient preventative, diagnostic and treatment strategies. Type 2 diabetes mellitus (T2DM) has been demonstrated to...

Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to...

Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In order to investigate the role of PPARs in endometrial cancer, we conducted a literature review using the MEDLINE and LIVIVO da...

Phytotherapy has long represented a widely accepted treatment alternative to conventional therapy. Bitter melon is a vine with potent antitumor effects against numerous cancer entities. To date, no review article has, however, been published on the role of bitter melon in breast and gynecological cancer prevention and therapy. The current work cons...

Simple Summary In this study, we investigated the potential of TLR4 to improve the treatment of hepatocellular carcinoma (HCC). HCC is a serious health concern worldwide, and finding new ways to combat it is crucial. Our study focused on understanding how TLR4 can enhance the effectiveness of immunotherapy, a treatment approach that harnesses the b...

Simple Summary MicroRNAs (miRNAs) show differential expression in various cancer entities and seemingly contribute to cancer development and/or progression. Nevertheless, their role in uterine sarcoma diagnosis and treatment is poorly understood. The current work represents the most comprehensive, up-to-date review of the literature on the particul...

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic target...

Polycystic ovary syndrome (PCOS) constitutes the most common endocrine disorder in women of reproductive age. Patients usually suffer from severe menstrual irregularities, skin conditions, and insulin resistance-associated health conditions. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins that regulate gene express...

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, with a grave prognosis and few effective treatment options. Organoids represent revolutionary three-dimensional cell culture models, derived from stem or differentiated cells and preserving the capacity to differentiate into the cell types of their tissue of...

Histone deacetylases (HDACs) are core epigenetic factors, with pivotal roles in the regulation of various cellular procedures, and their deregulation is a major trait in the acquisition of malignancy properties. In this study we attempt the first comprehensive evaluation of six class I (HDAC1, HDAC2, HDAC3) and II HDACs (HDAC4, HDAC5, HDAC6) expres...

Preeclampsia is a common pregnancy-related hypertensive disorder. Often presenting as preexisting or new-onset hypertension complicated by proteinuria and/or end-organ dysfunction, preeclampsia significantly correlates with maternal and perinatal morbidity and mortality. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor prote...

Pancreatic ductal adenocarcinoma (PDAC) is a major concern for health care systems worldwide, since its mortality remains unaltered despite the surge in cutting-edge science. The EPH/ephrin signaling system was first investigated in the 1980s. EPH/ephrins have been shown to exert bidirectional signaling and cell-to-cell communication, influencing c...

Lung cancer (LC) is the leading cause of cancer death in the United States. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest receptor tyrosine kinases (RTKs) family in mammals. EPHs along with their ligands, EPH-family receptor-interacting proteins (ephrins), have been found to be either up- or downregulated in LC cells...

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. Despite great advances in treatment strategies, therapeutic resistance and the gap between preclinical data and actual clinical efficacy justify the necessity of developing novel models for investigating OC. Organoids represent revolutionary three-dimensional cell cu...

Objectives Micro–computed tomography (micro-CT) is a novel, nondestructive, slide-free digital imaging modality that enables the acquisition of high-resolution, volumetric images of intact surgical tissue specimens. The aim of this systematic mapping review is to provide a comprehensive overview of the available literature on clinical applications...

Breast cancer (BC) is the most common malignant tumor in women. Erythropoietin-producing hepatocellular receptors (EPHs), receptor tyrosine kinases binding the membrane-bound proteins ephrins, are differentially expressed in BC, and correlate with carcinogenesis and tumor progression. With a view to examining available therapeutics targeting the EP...

Introduction: Nutritional status impacts the survival of patients with cancer. There are few studies that investigate the role of nutritional status on breast cancer survival in women with breast cancer, and even fewer regarding the impact of adhering to the Mediterranean diet (MD). The present study aims to assess the nutritional status, MD adhere...

(1) Background: The aim of the current study is to evaluate the immunohistochemical expression of Ki-67, CD-56, Cyclin-D1 and E-Cadherin in the tissues samples of pituitary adenomas (PAs) and its association with PAs clinical manifestation tumor size, invasiveness and the risk of recurrence. (2) Materials and Methods: Ninety-four patients who under...

Sarcomas are malignant tumors of mesenchymal origin that can occur at any age. The rarity of these tumors in combination with the vast number of histological subtypes render the study of sarcomas challenging. Organoids represent complex three-dimensional cell culture systems, deriving from stem cells and preserving the capacity to differentiate int...

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hem...

Gastrointestinal stromal tumors (GISTs) are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000. They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach, but also the small intestine, the omentum, mesentery and rectosigmoid. The available treatments for GIST are asso...

Introduction Osteosarcoma (OS) is the most common primary osseous malignant tumour, with high propensity to metastasise in lungs. Pulmonary micro-metastases are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have a...

Background: Recent advances demonstrate the role of chromatin regulators, including histone variants and histone chaperones, in cancer initiation and progression. Methods: Histone H3K4me3, histone variant centromere protein (CENP-A) and histone chaperones Holliday junction recognition protein (HJURP) as well as DAXX expression were examined immu...

Thymic Epithelial Tumors (TETs) represent a rare tumor family, originating from the epithelial component of the thymus gland. Clinicopathologically, they are segregated into six major subtypes, associated with distinct histological features and clinical outcomes. Their emergence and evolution are accompanied by the generation of a complex tumor mic...

Introduction Anti-EGFR targeted anti-cancer treatment is associated with various skin adverse events. Cetuximab is often associated with acneiform papules and skin disorders. Hypertrichosis cited in face pinnae and eyelash trichomegaly are seldom described. Case report A 72-year-old female cancer patient presented deteriorating facial-pinnae hyper...

The human PROX1 gene (Prospero homeobox gene 1) is a member of the homeobox transcription factor family. PROX1 plays a key role in the development of the lymphatic system and is primarily used as a lymphatic vessel marker. However, as the accumulating evidence indicates that PROX1 is also implicated in the tumorigenesis of various cancer types, the...

The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances in systemic therapy and surgery. This trend is fueled by the rise of an obesity wave which is prominent the Western populations and has reshaped the etiologic landscape of HCC. Interest in the nucleotide-binding domain leucine-ric...

Musculoskeletal sarcomas represent rare heterogenous malignancies of mesenchymal origin that can be divided in two distinct subtypes, bone and soft tissue sarcomas. Current treatment options combine the surgical excision of local tumors and multidrug chemotherapy to prevent metastatic widespread disease. Due to the grim prognosis that usually accom...

Uveal melanomas (UMs) comprise the most common primary intraocular malignancies in adults, with the eye representing the second most common site for melanoma, following the skin. Prognosis remains poor, with approximately half of the cases presenting with metastatic disease at the time of diagnosis. Erythropoietin-producing human hepatocellular rec...

Radiation-induced breast sarcomas (RIBS) are rare entities representing <1% of all primary breast malignancies, limiting most reports to small retrospective case series. They constitute a heterogeneous group of neoplasms, with high-grade angiosarcoma being the most common subtype. Other sarcoma histotypes, such as undifferentiated pleomorphic sarco...

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using t...

We conducted a retrospective tumor tissue analysis collected as part of the BRIM3 trial to evaluate the theragnostic significance of tumor-infiltrating lymphocytes (TILs) and melanoma cell proliferation. Using manual semi-quantitative analyses, we assessed the density of TILs by pathology review of tissue sections stained with hematoxylin and eosin...

Simple Summary Endometrial cancer (EC) is one of the main causes of cancer-related death among women. Despite the advances in gynecologic oncology, the incidence of EC is on the rise, and the relative 5-year survival remains unchanged in the last decade. This creates an urgent need for a deeper understanding of the pathogenesis of EC that will resu...

Melanoma is an aggressive malignant tumor, arising more commonly on the skin, while it can also occur on mucosal surfaces and the uveal tract of the eye. In the context of the unresectable and metastatic cases that account for the vast majority of melanoma-related deaths, the currently available therapeutic options are of limited value. The exponen...

Pancreatic Ductal Adenocarcinoma (PDAC) constitutes a leading cause of cancer death globally. Its mortality remains unaltered despite the considerable scientific progress made in the fields of diagnostics and treatment. Exosomes comprise of small extracellular vesicles secreted by nearly all cells; their cargo contains a vast array of biomolecules,...

Exosomes are cell-secreted nanoparticles containing various molecules including small vesicles, microRNAs (miRNAs), messenger RNAs or bioactive proteins which are thought to be of paramount importance for intercellular communication. The unique effects of exosomes in terms of cell penetration capacity, decreased immunogenicity and inherent stabilit...

Gynecological cancers represent some of the most common types of malignancy worldwide. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest subfamily of receptor tyrosine kinases, binding membrane-bound proteins called ephrins. EPHs/ephrins exhibit widespread expression in different cell types, playing an important role in...

Purpose: Endoscope-assisted transsphenoidal surgery over the last few years has led to more radical excision of pituitary adenomas (PAs) with a low complication rate. Systematic registration of complications by experienced surgical teams could help to improve this technique while ameliorating the patients' quality of life. Materials and methods:...

The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand (ephrins). Its significance in a wide variety of physiologic and pathologic processes has been recognized during the past decades. In carcinogenesis, EPH/ephrins coordinate a wide s...

Ongoing research continues to elucidate the complex role of ephrin receptors (EPHs) and their ligands (ephrins) in breast cancer pathogenesis, with their varying expression patterns implied to have an important impact on patients’ outcome. The current study aims to investigate the clinical significance of EPHA2, EPHA4, and EPHA7 expression in tripl...

Introduction: TRPV4 channels are calcium channels, activated by mechanical stress, that have been implicated in the pathogenesis of pulmonary inflammation. During resistive breathing (RB), increased mechanical stress is imposed on the lung, inducing lung injury. The role of TRPV4 channels in RB-induced lung injury is unknown. Materials and method...

Ephrin receptors (Ephs) are receptor tyrosine kinases (RTKs) implicated in tissue development and homeostasis, and they are aberrantly expressed in tumors. Here, immunohistochemical Eph type-A and -B expression in thymic epithelial tumors (TETs) was assessed and correlated with clinicopathological parameters. Tissue microarrays from 98 TETs were st...

Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Epigenetic alterations are implicated in endometrial cancer development and progression. Histone deacetylase inhibitors are a novel class of anticancer drugs that increase the level of histone acetylation in many cell types, thereby inducing c...

Soft tissue and bone sarcomas represent a group of aggressive neoplasms often accompanied by dismal patient prognosis, especially when distant metastases are present. Moreover, effective treatment can pose a challenge, as recurrences are frequent and almost half of patients present with advanced disease. Researchers have unveiled the molecular abno...

Introduction. Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has bee...

Background Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been s...

Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed...

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highes...

Background: Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role in carcinogenesis, and HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical settings. The aim of this study was t...

Pancreatic cancer is set to become the most lethal and common type of cancer worldwide. This is partly attributed to the mutational burden that affects core signaling pathways and the crosstalk of tumor cells with their surrounding microenvironment, but it is also due to modern eating habits. Hyperadiposity along with the constant rise in metabolic...

Pregnane X Receptor (PXR) belongs to the nuclear receptors' superfamily and mainly functions as a xenobiotic sensor activated by a variety of ligands. PXR is widely expressed in normal and malignant tissues. Drug metabolizing enzymes and transporters are also under PXR's regulation. Antineoplastic agents are of particular interest since cancer pati...

Histone deacetylases (HDACs) have long been implicated in tumorigenesis and tumor progression demonstrating their important participation in neoplasia. Therefore, numerous studies have been performed, highlighting the mechanism of HDACs action in tumor cells and demonstrating the potential role of HDAC inhibitors in the treatment of different cance...

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditiona...

ELAV-like protein 1, or HuR (human antigen R), is an RNA-binding protein encoded by the ELAVL1 gene in humans. One of its best functions is to stabilize mRNAs in order to regulate gene expression. HuR protein overexpression has undoubtedly been linked to an increased risk of tumor growth, progression, and metastasis, rendering it a potential therap...

Simple Summary There is an emerging need for new weapons in the battle against cancer; therefore, the discovery of new biomarkers with diagnostic, prognostic, and therapeutic value is a priority of current cancer research. An important task is to identify how quickly a tumour proliferates. A tumour’s proliferation rate is critical for grading and c...

Background: Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor, with over 20% of patients suffering from venous thromboembolism during the disease. Thus, low-molecular-weight heparin (LMWH) such as Tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approach to treating highly malignant and refractor...

Simple Summary Adrenocortical carcinoma is a rare but aggressive malignancy with poor outcomes even for patients with early-stage disease. Several immunotherapy clinical trials, many of which are still in progress, have yielded modest results so far. In-depth understanding of the tumor microenvironment in other cancer types has helped the scientifi...

Purpose: Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation i...

Salivary gland tumors (SGTs) comprise a group of rare neoplasms. Locally aggressive, recurrent and/or metastatic SGTs are notorious for their resistance to systemic therapy, making the need for carefully designed, prospective and randomized trials with useful predictive markers mandatory to define new effective therapeutic protocols. Histone Deacet...

Exosomes are extracellular vesicles, enriched in biomolecular cargo consisting of nucleic acids, proteins, and lipids, which take part in intercellular communication and play a crucial role in both physiologic functions and oncogenesis. Bladder cancer is the most common urinary malignancy and its incidence is steadily rising in developed countries....

Introduction: Uveal melanoma (UM) is the most common intraocular cancer and represents a discrete subtype of melanoma. Metastatic disease, which occurs in half of patients, has a dismal prognosis. Immunotherapy with immune checkpoint inhibitors has produced promising results in cutaneous melanoma but has failed to show analogous efficacy in metast...

Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) and FLI1 (Friend leukemia virus integration site 1) genes, leading to an EWS–FLI1 fused protein, which is associated with autophagy, a homeostatic and catabolic mecha...

Simple Summary Adenoid cystic carcinoma (ACC) is a rare but lethal salivary gland tumor, comprising less than 1% of head and neck neoplasms. It can affect several sites in the head and neck region, but the potential role of tumor site on survival and treatment response remains unclear and, to this day, the role that tumor location plays in treatmen...