Is collagenase-3 (MMP-13) expression in chondrosarcoma of the jaws a true marker for tumor aggressiveness?

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) play an important role in the modeling and remodeling of the extracellular matrix in both physiologic and pathologic states and thus plays an important role in tumor progression. Human collagenase-3 (MMP-13) is a member of matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes.</p> <p>Aim</p> <p>The present study was designed to investigate the expression MMP-13 and to correlate its expression with clinicopathological parameters in chondrosarcoma of the jaws.</p> <p>Methods</p> <p>Archival tumor tissues from 11 patients with chondrosarcoma of the jaws were analyzed by immunohistochemistry for the expression of MMP-13. Clinical information was obtained through the computerized retrospective database from the tumor registry between 1998 to 2006.</p> <p>Results</p> <p>Eight of 11 cases (72.8 %) of chondrosarcomas showed a positive reaction for MMP-13, whereas two cases of normal cartilage were negative for this collagenase. As regard the clinicopathological parameters, there was no correlation between MMP-13 expression and sex, age and tumor site. While, there were significant associations between MMP-13 expression and both of mitotic counts and necrosis. On the other hand, there was a significant difference between low and high grade tumors (P < 0.05) regarding MMP-13 expression. Also, there was no significant correlation between MMP-13 expression in primary lesions and their local recurrence.</p> <p>Conclusion</p> <p>MMP-13 is expressed in the majority of chondrosarcoma of the jaws. It is also noteworthy that the expression of MMP-13 may be related to tumor biological aggressiveness and used to aid in predicting patient's poor prognosis.</p

EVOLVING ROLE OF CAR T-CELL IN CANCER IMMUNOTHERAPY

Safety profiles of newly developed anti-cancer therapies is the main goal for efficient treatments to improve survival rates. Therefore, continuous efforts carried out to develop a therapeutic strategy with better outcomes. The concept of immune-oncology, which utilizes and enhances the capacity of human immune system was developed as an eventual opportunity to enhance remissions and limit the relaps of the disease. Later progression of cellular immunetherapies involve the introduction of genetically engineered T cells having chimeric antigen receptors (CARs) that embraced an antibody-derived antigen recognition domain connected to an internal T-cell signaling domain, so can recognize their targets with high degree of tumor selectivity. This approach showed vigorous antitumor outcomes and full recovery in end-stage patients suffering from liquid cancers as leukemia and lymphoma. However, still there is a challenge for bringing genetically modified T-cell immunotherapy to many patients with different tumor types including solid tumor. On other hand, studies indicated the potential to broaden T-cell–based therapies and foster for other possible applications beyond oncology as organ transplantation and autoimmunity. Therefore, this review aimed to illustrate the clinical applications, challenges, and approaches for more efficient clinical employment of CAR T cell therapies

The significance of Epstein Barr Virus (EBV) & DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC)

<p>Abstract</p> <p>Background</p> <p>Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood.</p> <p>Aim</p> <p>The present study was designed to investigate the role of EBV and DNA Topoisomerase II∝ (DNA-Topo II∝) during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs.</p> <p>Methods</p> <p>Using specific antibodies for EBV and DNA-Topo II∝, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry.</p> <p>Results</p> <p>DNA-Topo II∝ was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P < 0.01) in young aged labial tissues and significant (P ≤ 0.05) in gingival and not significant (P > 0.05) in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P < 0.001) and SCCs and controls (P < 0.001), also, significant differences could be observed between SCCs and OEDs. DNA-Topo II∝ expression was significantly higher in tumors of low differentiation versus tumors of moderate and high differentiation (P < 0.001), DNA-Topo II∝ expression was correlated with age, tumor size, tumor stage, node metastasis and tumor differentiation, but not with gender and tumor site. None of normal squamous epithelium (NSE) expressed EBV. Heterogenous reactivity for EBV was observed through the series of dysplasia and squamous cell carcinoma. Its expression increased progressively with lymph node metastasis and low tumor differentiation, but no significant association could be observed with other clinicopathological parameters. EBV protein expression was increased with elevated Topo II-∝ LI in OEDs and OSCCs. A tendency to positive correlation between EBV and Topo II∝ expression was observed in OEDs but not in OSCCs.</p> <p>Conclusion</p> <p>EBV and DNA Topo II-αLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.</p

Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model

<p>Abstract</p> <p>Background</p> <p>This work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).</p> <p>Methods</p> <p>Twenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.</p> <p>Results</p> <p>The reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.</p> <p>Conclusions</p> <p>Homing was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.</p

Knowledge about stroke among adults in Sharjah, United Arab Emirates

Background: In UAE, stroke is the second leading cause of disability after RTA, where annually 8,000 to 10,000 patients get a stroke. Our aim is to identify the knowledge levels of stroke among Sharjah’s adult citizens.Methods: Using self-administered questionnaires, in a cross-sectional design, a non-probability convenience sampling method was used to enrol subjects. Eligible subjects were above 18 years of age, comprehended Arabic or English, and are currently residing in Sharjah. The questionnaire was 17 questions structured in 5 sections which included: demographics, general knowledge, knowledge of signs and symptoms, risk factors, and appropriate response towards stroke. SPSS V.22 was used to analyse the data. Percentages, means, and ANOVA were used. A P-value less than 0.05 was considered to be statistically significant.Results: The study included 426 subjects, mean age was 35.1 years, 65.2% were females. 51.8% of the subjects claimed they know what stroke is, out of whom 24.3% provided incorrect descriptions. The mean knowledge level of signs and symptoms was 55.4%, and of risk factors was 40.6%. Visual disturbance was the least identified of the five signs and symptoms (38.0%). Female gender, African American race, and age above 60, were the least identified of the 8 risk factors (4.7%, 3.5%, 19.8% respectively). Better knowledge was associated with increased age and higher education. Conclusion: The majority of the sample showed an average to low level of knowledge. Such results indicate the importance of implementing more awareness programs that target younger age groups in the community

A comparative study of the effect of caudal dexmedetomidine versus morphine added to bupivacaine in pediatric infra-umbilical surgery

Background: One of the most commonly used regional anesthetic techniques in pediatric surgeries is the caudal epidural block. Its main disadvantage remains the short duration of action. Hence, different additives have been used. Dexmedetomidine is a potent as well as highly selective α2 adrenergic receptor agonist. The aim of this randomized, double-blinded, study was to compare the duration of postoperative analgesia of caudal dexmedetomidine versus morphine in combination with bupivacaine in pediatric patients undergoing lower abdominal or perineal surgery. Patients and Methods: A total of 50 pediatric patients 1-5 years old The American Society of Anesthesiologists status I, II scheduled for lower abdominal and perineal surgeries were included in the study. The patients were enrolled into 2 equal groups: Group A patients (n = 25) received dexmedetomidine with bupivacaine while Group B patients (n = 25) received morphine with bupivacaine. Patients were placed in a supine position then inhalational general anesthesia was induced, and laryngeal mask airway (LMA) was placed. Patients were then given caudal epidural analgesia. By the end of surgery reversal of muscle relaxation was done and the LMA was removed. Post-operatively, the sedation as well as pain score were observed and recorded. Results: The current study showed that minor complications were recorded in the post-anesthesia care unit; in addition, significantly longer periods of analgesia and sedation were detected in Group A. However, no significant differences in demographic data, as well as in the duration of surgery, and the time of emergence from anesthesia and patient condition during recovery were detected. Conclusion: The present study suggested that use of dexmedetomidine, during single dose injection, as an additive to the local anesthetic bupivacaine in caudal epidural analgesia prolongs the duration of post-operative analgesia following lower abdominal as well as perineal surgery compared with caudal morphine with no side-effects on the vital signs. Postoperative side effects were seen with caudal morphine injection rather than with dexmedetomidine