The Activation of Mesenchymal Stem Cells by Glioblastoma Microvesicles Alters Their Exosomal Secretion of miR-100-5p, miR-9-5p and let-7d-5p

Glioblastoma (GBM) is the most aggressive brain tumor, and despite initial response to chemo- and radio-therapy, the persistence of glioblastoma stem cells (GSCs) unfortunately always results in tumor recurrence. It is now largely admitted that tumor cells recruit normal cells, including mesenchymal stem cells (MSCs), and components of their environment, to participate in tumor progression, building up what is called the tumor microenvironment (TME). While growth factors and cytokines constitute essential messengers to pass on signals between tumor and TME, recent uncovering of extracellular vesicles (EVs), composed of microvesicles (MVs) and exosomes, opened new perspectives to define the modalities of this communication. In the GBM context particularly, we investigated what could be the nature of the EV exchange between GSCs and MSCs. We show that GSCs MVs can activate MSCs into cancer-associated fibroblasts (CAFs)-like cells, that subsequently increase their secretion of exosomes. Moreover, a significant decrease in anti-tumoral miR-100-5p, miR-9-5p and let-7d-5p was observed in these exosomes. This clearly suggests a miRNA-mediated GBM tumor promotion by MSCs exosomes, after their activation by GBM MVs.

Female Oncofertility: Current Understandings, Therapeutic Approaches, Controversies, and Future Perspectives

Recent advances in early detection and oncological therapies have ameliorated the survival rate of young cancer patients. Yet, ovarian impairment induced by chemotherapy and radiotherapy is still a challenging issue. This review, based on clinical and lab-based studies, summarizes the evidence of gonadotoxicity of chemoradiotherapy, the recent approaches, ongoing controversies, and future perspectives of fertility preservation (FP) in female patients who have experienced chemo- or radio-therapy. Existing data indicate that chemotherapeutic agents induce DNA alterations and massive follicle activation via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Meanwhile, the radiation causes ionizing damage, leading to germ cell loss. In addition to the well-established methods, numerous therapeutic approaches have been suggested, including minimizing the follicle loss in cryopreserved ovarian grafts after transplantation, in vitro activation or in vitro growing of follicles, artificial ovarian development, or fertoprotective adjuvant to prevent ovarian damage from chemotherapy. Some reports have revealed positive outcomes from these therapies, whereas others have demonstrated conflictions. Future perspectives are improving the live birth rate of FP, especially in patients with adverse ovarian reserve, eliminating the risk of malignancy reintroducing, and increasing society’s awareness of FP importance.

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

NK cell upraise in the dark world of cancer stem cells

One of the obstacles in treating different cancers, especially solid tumors, is cancer stem cells (CSCs) with their ability in resistance to chemo/radio therapy. The efforts for finding advanced treatments to overcome these cells have led to the emergence of advanced immune cell-based therapy (AICBT). Today, NK cells have become the center of attention since they have been proved to show an appropriate cytotoxicity against different cancer types as well as the capability of detecting and killing CSCs. Attempts for reaching an off-the-shelf source of NK cells have been made and resulted in the emergence of chimeric antigen receptor natural killer cells (CAR-NK cells). The CAR technology has then been used for generating more cytotoxic and efficient NK cells, which has increased the hope for cancer treatment. Since utilizing this advanced technology to target CSCs have been published in few studies, the present study has focused on discussing the characteristics of CSCs, which are detected and targeted by NK cells, the advantages and restrictions of using CAR-NK cells in CSCs treatment and the probable challenges in this process.

P-OGC60 Predicting the risk of venous thromboembolism during neoadjuvant therapy for oesophagogastric cancer

Background Locally advanced oesophageal cancer is usually treated with neoadjuvant treatment (NAT) followed by surgery. Venous thromboembolism (VTE) is a recognised complication in these patients. Those who develop VTE may have an inferior vena cava filter placed prior to surgery to reduce the risk of further complications. This study aimed to identify specific risks for VTE during (NAT) for oesophagogastric cancer (OGC) and whether this increases postoperative morbidity. Methods Patients undergoing NAT for OGC followed by surgery at a single high-volume centre between January 2015 and June 2020 were identified from a prospectively maintained database. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors for the development of VTE as well as the association between diagnosis of VTE and morbidity. Results The incidence of VTE in this cohort was 6.7% (27/406). Independent risk factors for developing VTE in multivariable analysis were BMI – OR 1.093 (p = 0.045) and age – OR 1.067 (p = 0.019). Type of chemo(radio)therapy regimen used, pT, pN stage, previous history of ischaemic heart disease or being an active smoker at diagnosis was not associated with VTE occurrence. Diagnosis of VTE during neoadjuvant treatment was not associated with a higher risk of developing a serious postoperative complication (Clavien-Dindo grade III and above) (p = 0.699). Conclusions Patients with a raised BMI or older age are at higher risk of developing VTE during NAT for OGC. These patients must be appropriately counseled on the higher risk of VTE prior to commencing NAT. However, the development of a VTE does not appear to confer any additional post-operative complication risk.

Effect of Palliative Radiotherapy in controlling pain of Malignancy

Background: Radiation therapy reported to be an effective in palliating pain. Objective: To describe roles of palliative radiotherapy in controlling pain in metastatic cancerous patients, and evaluation of radio-therapy doses in pain management. Methods: A prospective observational study carried out at the Baghdad Radiotherapy and Nuclear Medicine Center/Baghdad Medical City Complex, Baghdad, Iraq, from 1st of December 2018 to 30th of May 2019. 88 Patients, were included. Patients were assessed before applying radiotherapy, and at the end of treatment. Pain scoring used from 0 to 10. Kaplan Meier survival curve used. Result: The mean±SD of age was 55.44±11.1 years, and the most frequent age group was 41-50years as 37(42.1%). Breast cancer come in 1st rank cases studied in our research as 35(39.8%). 42(47.7%) of patients received radio-therapy on metastatic spine vertebral lesions. Sharp pain, frequent pain, pain at night were the commonest. Before treatment, the most common scoring was (8) in 33(37.5%) patients, while after palliative radio-therapy the scoring shift downward. Radio-therapy dose of 1200 cGy improved overall survival of patients in this study to 21.5 weeks (95%CI= 20.2-22.8). Conclusion: Radiotherapy is effective in palliative therapy. A dose of 1200 cGy improved overall survival of patients in this study to 21.5 weeks.

Knowledge about Prescription of the Antibiotic for Endodontic’s Treatment among Final Year Students.

Background: Since antibiotic’s discovery, they have been widely utilized for treatment of the odontogenic infections. Writing a prescription is a vital determining factor of the good doctor/clinician. Drug Prescription is a dynamic and personalized clinical process, which is established as a result of necessities of the patient & acquaintance of practitioner & is also the component of curriculum of graduation. Aim: To evaluate and assess knowledge about prescription of the antibiotic during the endodontics’s treatment and the errors made by final year students at the dental hospital. Setting: Multan Medical & Dental College Multan Methodology: This survey-based research was led among 48 students of Multan Dental College Multan. A form was designed, regarding pattern of the antibiotic’s prescription & conditions/situations for which the drugs were recommended by students of final year. Results: The medication of choice was mostly Amoxicillin alone (75%) and Amoxicillin + clavulanic acid (55%). Most of antibiotic prescriptions were written for Perio-endo lesion (85%), acute apical abscess (80%). Chronic apical abscess with sinus tract (80%), Ch. apical abscess with periodontitis (65%), Patients with swelling & difficulty in swallowing (62%). In this study the greatest numbers of antibiotics prescribed were prophylactically for congenital cardiac sicknesses 69.7%, and uncontrolled diabetes mellitus 60%. Prosthetic joint in past 2 years 40% & Chemo/radio therapy 30%. Conclusion: There is a dearth of knowledge as well as information concerning the suitable indication, kind, & dose of the antibiotics in practice of dentistry. The curriculum should propose great accent on prescription, and decent prescription practices should also be taught in clinical rotation’s, using actual or imaginary cases. Keywords: Antibiotics, Endodontics, Prescription writing, prophylaxis, Root canal treatment (RCT)

Impact of chemotherapy and radiotherapy on the survival of elderly esophageal cancer patients undergoing surgery: a SEER database analysis

Background Esophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis. Methods A total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram’s risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared. Results A better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45–0.68, P < 0.001), especially for those with tumors characterized by poor differentiation, large tumor size, advanced T staging, lymphatic metastasis, and distant metastasis (HR: 0.48, 95% CI 0.39–0.59, P < 0.001), while no benefit was observed among the low-risk patients. Furthermore, the newly established nomogram model might be better than the TNM (6th revision) staging system but more data needed. Conclusion Aggressive treatments, such as surgery, chemotherapy, and radiotherapy, were considered effective for selected elderly patients with EC according to the newly established nomogram model.

Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma – A Review

Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.

Esophageal microbiota composition and outcome of esophageal cancer treatment: a systematic review

Summary Background: The role of esophageal microbiota in esophageal cancer treatment is gaining renewed interest, largely driven by novel DNA-based microbiota analysis techniques. The aim of this systematic review is to provide an overview of current literature on the possible association between esophageal microbiota and outcome of esophageal cancer treatment, including tumor response to (neo)adjuvant chemo(radio)therapy, short-term surgery-related complications, and long-term oncological outcome. Methods: A systematic review of literature was performed, bibliographic databases were searched and relevant articles were selected by two independent researchers. The Newcastle-Ottawa scale was used to estimate the quality of included studies. Results: The search yielded 1303 articles, after selection and cross-referencing, five articles were included for qualitative synthesis and four studies were considered of good quality. Two articles addressed tumor response to neoadjuvant chemotherapy and described a correlation between high intratumoral Fusobacterium nucleatum levels and a poor response. One study assessed surgery-related complications, in which no direct association between esophageal microbiota and occurrence of complications was observed. Three studies described a correlation between shortened survival and high levels of intratumoral F. nucleatum, a low abundance of Proteobacteria and high abundances of Prevotella and Streptococcus species. Conclusions: Current evidence points towards an association between esophageal microbiota and outcome of esophageal cancer treatment and justifies further research. Whether screening of the individual esophageal microbiota can be used to identify and select patients with a predisposition for adverse outcome needs to be further investigated. This could lead to the development of microbiota-based interventions to optimize esophageal microbiota composition, thereby improving outcome of patients with esophageal cancer.