Evaluation of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

BACKGROUND/AIM: Triple negative breast cancer belongs to the most aggressive breast cancer forms. Histone deacetylases (HDACs) constitute a class of enzymes that exhibit a significant role in breast cancer genesis and progression. In this study, we aimed at assessing the clinical importance of HDAC-2 in triple negative breast cancer. MATERIALS AND METHODS: A total of 138 breast cancer specimens were examined on an immunohistochemical basis. A statistical analysis was performed in order to examine the association between HDAC-2 and the survival and clinicopathological features of the patients. RESULTS: Increased HDAC-2 expression was observed in every fourth case of triple negative breast cancer with positive HDAC-2 staining, whereas only 12 out of 98 non-triple negative breast cancer samples showed high HDAC-2 expression. HDAC-2 overexpression correlated with prolonged overall survival (OS) and disease-free survival (DFS) in triple negative breast cancer. CONCLUSIONS: High HDAC-2 levels in triple negative breast cancer seem to positively influence patient survival, disease stage and recurrence.

Synchronous Insulinoma and Glucagonoma: A Review of the Literature.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

Liver Cancer and Pregnancy: A Review of the Literature.

BACKGROUND/AIM: Liver cancer constitutes one of the leading cancers globally. During pregnancy, however, liver cancer is an absolute rarity, with very few cases reported in the international literature. The aim of the present review was to provide a useful update and summarize all case studies of liver cancer in pregnancy published between 2012-2023. MATERIALS AND METHODS: A literature review was conducted using the MEDLINE, LIVIVO, and Google Scholar databases. Solely case reports and case studies written in the English language that explicitly reported on the presence of histologically confirmed HCC or intrahepatic cholangiocarcinoma during pregnancy were included in the data analysis. RESULTS: After detailed evaluation, a total of 35 reported cases of liver cancer during pregnancy were identified, hence bringing the total number of reported cases globally to 83. Oncological challenges during pregnancy call for an interdisciplinary approach. Although the desire to preserve the pregnancy should be taken into consideration, specialists need to evaluate maternal and fetal well-being and choose the optimal oncological treatment with the least dangers for both the maternal and fetal safety. CONCLUSION: The present review proves that, despite its scarcity, liver cancer may always occur during pregnancy and clinicians should, therefore, remain vigilant and endeavor to detect and evaluate any hepatic mass or symptoms of liver cancer promptly and exhaustively.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy.

Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review is to study the role of HDACIs in the treatment of cervical cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "histone deacetylase" and "cervical cancer", we managed to identify 95 studies published between 2001 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HDACIs as treatment agents for cervical cancer. Both well-established and novel HDACIs seem to represent modern, efficacious anticancer drugs, which, alone or in combination with other treatments, may successfully inhibit cervical cancer cell growth, induce cell cycle arrest, and provoke apoptosis. In summary, histone deacetylases seem to represent promising future treatment targets in cervical cancer.

FDA-Approved Monoclonal Antibodies for Unresectable Hepatocellular Carcinoma: What Do We Know So Far?

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Clinical Significance of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

BACKGROUND/AIM: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). MATERIALS AND METHODS: A total of 118 BC specimens were examined immunohistochemically. A statistical analysis was conducted in order to examine the relation between HDAC-2 and the clinicopathological features and survival of the patients. RESULTS: Higher HDAC-2 expression was related to lobular histological type of cancer, grade III, and stage III BC. In addition, the disease-free period and overall survival were curtailed and negatively related to the over-expression of HDAC-2. Other factors correlating with worse survival were histological types other than ductal or lobular, and the stage of the disease. CONCLUSIONS: This study showed a relationship between HDAC-2 and BC. Further studies are required in order to eventually potentiate the role of HDACIs as anticancer agents in BC.

Liver Transplantation and Budd-Chiari Syndrome: When the Cause Becomes the Solution.

Budd-Chiari syndrome consists a rare medical entity which has an estimated incidence of 0.1 to 10 people per million every year. It is defined by the obstruction of the flow in the inferior vena cava or the hepatic veins. Various classifications have been proposed. So, it can be acute or chronic and primary or secondary. Iatrogenic, a subtype of secondary Budd-Chiari syndrome, is caused by various medical interventions, including liver transplantation. On the other hand, liver transplantation is the ultimate therapeutic management of Budd-Chiari syndrome. Finally, a medical paradox and a vicious circle has been created. Liver transplantation can potentially be both the cause and treatment of Budd-Chiari syndrome. Budd-Chiari syndrome is simultaneously the cause and complication of liver transplantation. Our aim is to describe this double role of liver transplantation in Budd-Chiari syndrome and to acknowledge that a high degree of clinical suspicion is necessary for the proper recognition and management of this life-threatening condition.

The Role of SNHG15 in the Pathogenesis of Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides which cannot be translated into proteins. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA whose dysregulation has been found to have an important impact on carcinogenesis and affect the prognosis of cancer patients in various cancer types. Hepatocellular carcinoma (HCC) is one of the most common cancers with a poor long-term prognosis, while the best prognostic factor of the disease is its early diagnosis and surgery. Consequently, the investigation of the mechanisms of hepatocarcinogenesis, as well as the discovery of efficient molecular markers and therapeutic targets are of great significance. An extensive literature search was performed in MEDLINE in order to identify clinical studies that tried to reveal the role of SNHG15 in HCC. We used keywords such as 'HCC', 'hepatocellular carcinoma', 'SNHG15' and 'clinical study'. Finally, we included four studies written in English, published during the period 2016-2021. It was revealed that SNHG15 is related to the appearance of HCC via different routes and its over-expression affects the overall survival of the patients. More assays are required in order to clarify the potential role of SNHG15 as a prognostic tool and therapeutic target in HCC.

Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.

Operating on Jehovah's Witnesses: A Challenging Surgical Issue.

Blood transfusion is often utilized in surgery. Greece is the second-highest consumer of blood components in Europe. It has been shown that at least half of all transfusions are unnecessary and could be avoided. Jehovah's Witnesses (JWs) are a Christian religion that do not accept transfusion of whole blood or the four primary components of blood-namely, red blood cells, white blood cells, platelets, and plasma. This a retrospective study from September of 2015 to January of 2018, analyzing all JWs who underwent an elective operation at the Second Department of Propaedeutic Surgery in Laiko University Hospital. Twenty-nine (Rogers et al. in NCCN Guidelines Version 2.2014 Cancer- and Chemotherapy-Induced Anemia. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network, Fort Washington, 2013) JW patients, 23 females (74.1%) and eight males, were operated on during the aforementioned period. The median ASA score was 1 (range 1-3), and only two of the patients needed postoperative monitoring in the ICU. Almost half of the patients (45.1%) needed iron infusion and EPO injection preoperatively. Two patients presented with postoperative complications, with no postoperative deaths. In conclusion, we found that surgery, in our small group of JW patients, was safe and successful despite the lack of blood transfusion. Techniques developed to treat JW patients should be more widely used to improve clinical outcomes and reduce costs to the healthcare system.

Role of histone deacetylase inhibitors in diabetic cardiomyopathy in experimental models (Review).

In diabetes, metabolic dysregulation, caused by hyperglycemia, leads to both structural and functional changes in cardiomyocytes and subsequently leads to the development of cardiomyopathy. Histone deacetylases (HDAC) are enzymes that regulate gene transcription. Their actions have been examined in the development of multiple disorders, such as cardiovascular diseases and diabetes. The use of HDAC inhibitors (HDACIs), as potential therapeutic agents against disease progression has yielded promising results. The present review article reports preclinical trials identified in which HDACIs were administered to mice suffering from diabetic cardiomyopathy (DCM), and discusses the role and mechanisms of action of HDAC and HDACIs in DCM. A review of the literature was performed using the PubMed database, aiming to identify publications in the English language concerning the role of HDACIs in DCM. More specifically, key words, separately and in various combinations, such as HDACIs, HDAC, diabetes, cardiomyopathy, heart failure and ischemia/reperfusion injury, were used. Furthermore, the references from all the articles were cross-checked in order to include any other eligible studies. The full-text articles assessed for eligibility were eight, covering the period from 2015 to 2019; finally, all of them were included. The use of HDACIs exhibited encouraging results against DCM progression through various mechanisms, including the reduction of reactive oxygen species generation, inflammatory cytokine production and fibrosis, and an increase in autophagy and angiogenesis.

Insulin-like growth factor-I and wound healing, a potential answer to non-healing wounds: A systematic review of the literature and future perspectives.

The induction of wound healing by insulin-like growth factor-I (IGF-I) has been demonstrated in several animal studies; however, there are disproportionately fewer studies assessing its value in humans. The aim of the present review is to provide a comprehensive summary of all the available evidence pertaining to the effects of IGF-I administration on the process of wound anaplasias, both in human tissues in vivo and in cells in vitro. A systematic search of Medline, Scopus and Google Scholar was performed for relevant studies published until May 2020. Overall, 11 studies were included. Of these, 2 studies were conducted in human subjects, whereas the rest of them were performed using in vitro models of human cell lines. All studies demonstrated a positive association between IGF-I and wound anaplasias; IGF-I promoted the migration of keratinocytes, thus playing an important role in wound epithelialization as well as enabling wound bed contraction, and it also stimulated hyaluronan synthesis. The wound healing-promoting effect of IGF-I may be a great asset in dealing with the healing of challenging wounds; thus, this type of treatment could be extremely useful in addressing patients with large burn wounds, chronic diabetic ulcers and patients with impaired wound healing. Nevertheless, the route of recombinant IGF-I administration, the recommended dosage, as well as the indications for clinical use of this growth factor remain to be determined and thus, additional clinical trials are required, with a focus on the medical use of recombinant IGF-I in wound anaplasias.

MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease.

BACKGROUND: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. PATIENTS AND METHODS: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. RESULTS: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056-0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049-0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. CONCLUSIONS: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality.

BACKGROUND: Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. METHODS: One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. RESULTS: Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401-8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. CONCLUSIONS: High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

Performing modified fontan before six years of age leads to superior long-term exercise capacity.

We investigated the influence of age at Fontan completion on the exercise capacity of patients who underwent a Fontan operation. Our study demonstrated that age at the time of the Fontan operation significantly affects the peak oxygen consumption at mid-term follow up and that exercise capacity is superior in patients who have undergone Fontan completion at an earlier age. These findings provide support for recommendations to perform Fontan completion procedures relatively early.

L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease.

Background: Metastatic disease in colorectal cancer represents a major cause of significant cancer-associated morbidity and mortality. L1CAM is a stem cell marker, cell adhesion molecule, belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAM) and it is aberrantly expressed in several different types of human solid tumors. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer.Patients and methods: Surgical specimens of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry and the results were correlated with clinical and survival data.Results: L1CAM expression was significantly correlated with advanced stage of disease (p < .001), higher T classification (p = .040), the presence of lymph node (p < .001) and distant metastasis (p = .011). Patients displaying high L1CAM expression demonstrated a dismal three-year progression free survival (29.7% vs 87.1%, p < .001) and five-year overall survival (39.9% vs 87.7%, p < .001). Multivariate analysis using Cox proportional hazard models revealed high L1CAM expression as a prognostic marker of dismal progression free (HR 0.187, 95%CI = 0.075-0.467, p < .0001) and overall survival (HR 0.154, 95%CI = 0.049-0.483, p = .001) independent of other clinicopathological characteristics. Subgroup analysis comprised of patients with early stage disease only presented as well significantly worse progression free and overall survival when L1CAM exhibited high expression.Conclusions: Colorectal cancer patients displaying high expression of L1CAM harbor high risk for metastasis already in early stage disease identifying therefore a group of patients prone to dismal prognosis.