Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Background: Several studies have highlighted hyperthermia’s ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. Materials and Methods: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia’s therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. Results: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. Conclusion: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage

Achaiki Iatriki : official publication of the medical society of western Greece and Peloponnesus

In the current issue, the editorial by Cauchi et al. argues for eco-friendly measures in endoscopy and emphasies the role of healthcare providers in reducing waste. The editorial adeptly employs the three Rs (Reduce, Reuse, Recycle) framework to tackle waste management, offering practical solutions. The editorial by Milionis et al. focuses on the reverse cascade screening for paediatric familial hypercholesterolaemia (FH), which is an upcoming tool for public health. Advantages, practices, and challenges regarding FH are thoroughly discussed. Lastly, the editorial by Fousekis et al. presents the main aspects of a chronic immune-mediated cutaneous disease, dermatitis herpetiformis (DH), which constitutes an extraintestinal manifestation of celiac disease, including its diagnosis, pathogenesis, and management. Moreover, this issue includes three review articles. The review article by Krontira et al. discusses the evolving data on the epidemiology, diagnostic approach and appropriate management of foreign body and caustic substance ingestion, based on updated guidelines published by gastroenterological and endoscopic societies. The review by Halliasos et al. provides data on the clinical presentation, diagnosis, and management of metastatic acute spinal cord compression, focusing on the importance of a multidisciplinary team approach, including spine surgeons, radiation oncologists, medical oncologists, palliative care clinicians, physiotherapists, and psychologists. Lastly, the review by Schinas et al. outlines the potential of immune modulation in the treatment of infections and the need for individualised approaches in the modern world of personalised medicine by examining some of the key strategies and immune-based therapies being developed to combat infectious diseases.peer-reviewe

Study on the expression of proteins involved in angiogenesis in gastric adenocarcinoma: correlation with clinical parameters

Angiogenesis is a complex process, depending on a great variety of angiogenic factors, one of the most important being the vascular endothelial growth factor A (VEGF-A), which acts through its specific receptors (VEGFR-1 and VEGFR-2). Several previous studies showed expression of VEGF-A in tumor cells of gastric carcinomas and correlations of VEGF-A with the micro vessel density (MVD). However, there are contradictory results as far as it concerns the prognostic value of VEGF-A, its receptors and MVD.Therefore, in the present study we analyzed 145 cases of gastric carcinomas for 1) the immunohistochemical expression of VEGF-A, VEGFR-1, VEGFR-2, p53 and Ki-67 proteins and 2) the MVD with the immunohistochemical markers CD34 and CD105 (MVD-CD34 and MVD-CD105) to gain further insight on the pathogenesis of this tumor. Moreover, the results were correlated to clinicοpathological parameters and clinical outcome of the patients.Expression of VEGF-A, VEGFR-1, VEGFR-2, p53 and Ki-67 proteins in tumor cells was detected in 123/145 (84.8%), 127/144 (88.2%), 105/143 (73.4%), 104/145 (71.7%) and 143/145 (98.6%) cases, respectively. The MVD-CD34 and the MVD-CD105 were 64.99 and 23.56, respectively. Positive correlations were found between VEGF-A and VEGFR-1, VEGFR-2, p53, Ki-67 and MVD-CD105 (p=0.002, p=0.046, p=0,045, p<0.001 and p=0.024, respectively) and between MVD-CD105 and MVD-CD34, Ki-67 and p53 (p<0.001, p<0.001 and p<0.001, respectively). Similar correlation was found between VEGFR-1 and VEGFR-2 (p<0.001).Analysis of protein expressions and MVD of the tumor with clinicopathological parameters showed that, VEGF-A expression was correlated with the clinical stage (p=0.007), VEGFR-1 expression with the histological grade and histological type of the tumor (p=0.037 and p=0.002, respectively), VEGFR-2 expression with the vascular invasion (p=0.045), and Ki-67 expression with the histological type and the vascular invasion (p=0.016 and p=0.032, respectively). In addition, the expression of VEGFR-2 and p53 proteins were correlated with prognosis. VEGFR-2 and p53 were found to be independent predictor factors of unfavourable clinical outcome.The results of the present study suggests an important role of angiogenesis in the pathogenesis of gastric carcinoma. Expression of pro-angiogenic proteins VEGF-A, VEGFR-1 and VEGFR-2 by tumor cells is a common event. VEGF-A produced by tumour cell may act as paracrine and autocrine growth factor in gastric adenocarcinoma by promoting angiogenesis and tumor cell proliferation through its receptors. Moreover, protein expression of VEGFR-2 and p53 are independent predictor factors of unfavorable clinical outcome in gastric carcinomas.Η αγγειογένεση είναι μια σύνθετη κυτταρική διαδικασία, η οποία ρυθμίζεται από διαφόρους αγγειογενετικούς παράγοντες, σημαντικότερος των οποίων είναι ο αγγειακός ενδοθηλιακός παράγοντας Α (vascular endothelial growth factor A, VEGF-A), ο οποίος δρα μέσω των εξειδικευμένων υποδοχέων του, VEGFR-1 και VEGFR-2. Αρκετές προηγούμενες μελέτες έδειξαν ότι έκφραση του VEGF-A στα νεοπλασματικά κύτταρα των γαστρικών καρκινωμάτων και συσχέτιση της έκφρασης του VEGF-A με την μικροαγγειακή πυκνότητα (micro vessel density, MVD). Τα αποτελέσματα όσον αφορά την προγνωστική αξία της έκφρασης του VEGF-A, των υποδοχέων του και της MVD είναι αντιφατικά.Στην παρούσα εργασία μελετήθηκαν σε 145 περιπτώσεις γαστρικών καρκινωμάτων 1) η ανοσοϊστοχημική έκφραση των πρωτεϊνών VEGF-A, VEGFR-1, VEGFR-2, p53 και Ki-67 και 2) η MVD με τους ανοσοϊστοχημικούς δείκτες CD34 και CD105 (MVD-CD34 και MVD-CD105) προκειμένου να διερευνηθούν περαιτέρω παθογενετικοί μηχανισμοί των καρκινωμάτων αυτών. Επιπλέον, τα ευρήματα συσχετίσθηκαν με κλινικοπαθολογοανατομικές παραμέτρους και την κλινική έκβαση των ασθενών με σκοπό την διερεύνηση της προγνωστικής αξίας της πρωτεϊνικής έκφρασης των VEGF-A, VEGFR-1 και VEGFR-2, καθώς και της MVD στα καρκινώματα του στομάχου.Έκφραση των πρωτεϊνών VEGF-A, VEGFR-1, VEGFR-2, p53 και Ki-67 στα νεοπλασματικά κύτταρα ανιχνεύθηκε σε 123/145 (84.8%), 127/144 (88.2%), 105/143 (73.4%), 104/145 (71.7%) και 143/145 (98.6%) περιπτώσεις, αντίστοιχα. Η MVD-CD34 και η MVD-CD105 ήταν 64.99 και 23.56, αντίστοιχα. Θετικές συσχετίσεις βρέθηκαν μεταξύ των VEGF-A και VEGFR-1, VEGFR-2, p53, Ki-67 και MVD-CD105 (p=0.002, p=0.046, p=0,045, p<0.001 και p=0.024, αντίστοιχα) και μεταξύ της MVD-CD105 και MVD-CD34, Ki-67 και p53 (p<0.001, p<0.001 και p<0.001, αντίστοιχα). Παρόμοια συσχέτιση βρέθηκε μεταξύ των υποδοχέων VEGFR-1 και VEGFR-2 (p<0.001).Ανάλυση της έκφρασης των πρωτεϊνών και της MVD του όγκου με κλινικοπαθολογοανατομικές παραμέτρους έδειξε ότι η έκφραση του VEGF-A συσχετίζεται με το κλινικό στάδιο (p=0.007), η έκφραση του VEGFR-1 με τον ιστολογικό βαθμό κακοήθειας και τον ιστολογικό τύπο του καρκινώματος (p=0.037 και p=0.002, αντίστοιχα), η έκφραση του VEGFR-2 με τη νεοπλασματική διήθηση αγγείων (p=0.045) και η έκφραση του Ki-67 με τον ιστολογικό τύπο και την νεοπλασματική διήθηση αγγείων (p=0.016 και p=0.032, αντίστοιχα). Επιπρόσθετα, αναδεικνύεται ότι τα επίπεδα έκφρασης των πρωτεϊνών VEGFR-2 και p53 συσχετίζονται με την πρόγνωση και αποτελούν ανεξάρτητους προγνωστικούς δείκτες δυσμενούς κλινικής έκβασης.Η πρωτεΐνη VEGF-Α και οι υποδοχείς της, VEGFR-1 και VEGFR-2, εκφράζονται στα νεοπλασματικά κύτταρα στην πλειονότητα των γαστρικών καρκινωμάτων και πιθανώς να έχουν παρακρινή και αυτοκρινή δράση επάγοντας την αγγειογένεση και τον κυτταρικό πολλαπλασιασμό των νεοπλασματικών κυττάρων. Τα επίπεδα έκφρασης των VEGFR-2 και p53 σχετίζονται με την πρόγνωση και είναι ανεξάρτητοι προγνωστικοί δείκτες δυσμενούς κλινικής έκβασης των γαστρικών καρκινωμάτων

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient’s disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum β-human chorionic gonadotropin enabled a correct diagnosis

Antitumor Potential of Lippia citriodora Essential Oil in Breast Tumor-Bearing Mice

Lippia citriodora is a flowering plant cultivated for its lemon-scented leaves and used in folk medicine for the preparation of tea for the alleviation of symptoms of gastrointestinal disorders, cold, and asthma. The oil extracted from the plant leaves was shown to possess antioxidant potential and to exert antiproliferative activity against breast cancer. The aim of this study was to further investigate potential antitumor effects of L. citriodora oil (LCO) on breast cancer. The in vitro antiproliferative activity of LCO was examined against murine DA3 breast cancer cells by the sulforhodamine B assay. We further explored the LCO’s pro-apoptotic potential with the Annexin-PI method. The LCO’s anti-migratory effect was assessed by the wound-healing assay. LCO was found to inhibit the growth of DA3 cells in vitro, attenuate their migration, and induce apoptosis. Finally, oral administration of LCO for 14 days in mice inhibited by 55% the size of developing tumors in the DA3 murine tumor model. Noteworthy, in the tumor tissue of LCO-treated mice the apoptotic marker cleaved caspase-3 was elevated, while a reduced protein expression of survivin was observed. These results indicate that LCO, as a source of bioactive compounds, has a very interesting nutraceutical potential

Intraoperative Flow Cytometry for the Rapid Diagnosis and Validation of Surgical Clearance of Non-Melanoma Skin Cancer: A Prospective Clinical Feasibility Study

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in humans, with a high global incidence. We present a prospective clinical feasibility study on the use of intraoperative flow cytometry (iFC) for the instant diagnosis of NMSC and its complete surgical clearance. Flow cytometry, a laser-based technique, quantifies cell features, which has applications in cancer research. This study aim is to explore the potential applicability of iFC in detecting and characterizing NMSC and its surgical margins. In total, 30 patients who underwent diagnosis for NMSC were recruited. The method demonstrated high sensitivity (95.2%) and specificity (87.1%), with an accuracy of 91.1%, as confirmed with a receiver operating characteristic curve analysis. The results also indicated that most tumors were diploid, with two cases being hypoploid. The average G0/G1 fractions for normal and tumor tissue samples were 96.03 ± 0.30% and 88.03 ± 1.29%, respectively, with the tumor index escalating from 3.89 ± 0.30% to 11.95 ± 1.29% in cancerous cells. These findings underscore iFC’s capability for precise intraoperative NMSC characterization and margin evaluation, promising enhanced complete tumor excision rates. Given the technique’s successful application in various other malignancies, its implementation in NMSC diagnosis and treatment holds significant promise and warrants further research in clinical trials

Circulating Tumor DNA in the Management of Early-Stage Breast Cancer

Liquid biopsies refer to the isolation and analysis of tumor-derived biological material from body fluids, most commonly blood, in order to provide clinically valuable information for the management of cancer patients. Their non-invasive nature allows to overcome the limitations of tissue biopsy and complement the latter in guiding therapeutic decision-making. In the past years, several studies have demonstrated that circulating tumor DNA (ctDNA) detection can be used in the clinical setting to improve patient prognosis and monitor therapy response, especially in metastatic cancers. With the advent of significant technological advances in assay development, ctDNA can now be accurately and reliably identified in early-stage cancers despite its low levels in the bloodstream. In this review, we discuss the most important studies that highlight the potential clinical utility of ctDNA in early-stage breast cancer focusing on early diagnosis, detection of minimal residual disease and prediction of metastatic relapse. We also offer a concise description of the most sensitive techniques that are deemed appropriate for ctDNA detection in early-stage cancer and we examine their advantages and disadvantages, as they have been employed in various studies. Finally, we discuss future perspectives on how ctDNA could be better integrated into the everyday oncology practice

Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models

Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituentsproliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrceneinduced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer

Nueva Alcarria: Año XXXI Número 1642 - 1970 mayo 23

In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia’s therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction