Purpose: Pigment epithelial-derived factor (PEDF) is a potent angiogenesis inhibitor with multiple other functions, some of which enhance tumor growth. Our previous studies mapped PEDF antiangiogenic and prosurvival activities to distinct epitopes. This study was aimed to determine the minimal fragment of PEDF, which maintains antiangiogenic and antitumor efficacy. Experimental Design: We analyzed antigenicity, hydrophilicity, and charge distribution of the angioinhibitory epitope (the 34-mer) and designed three peptides covering its COOH terminus, P14, P18, and P23. We analyzed their ability to block endothelial cell chemotaxis and induce apoptosis in vitro and their antiangiogenic activity in vivo. The selected peptide was tested for the antitumor activity against mildly aggressive xenografted prostate carcinoma and highly aggressive renal cell carcinoma. To verify that P18 acts in the same manner as PEDF, we used immunohistochemistry to measure PEDF targets, vascular endothelial growth factor receptor 2, and CD95 ligand expression in P18-treated vasculature. Results: P14 and P18 blocked endothelial cell chemotaxis; P18 and P23 induced apoptosis. P18 showed the highest IC 50 and blocked angiogenesis in vivo : P23 was inactive and P14 was proangiogenic. P18 increased the production of CD95 ligand and reduced the expression of vascular endothelial growth factor receptor 2 by the endothelial cells in vivo. In tumor studies, P18 was more effective in blocking the angiogenesis and growth of the prostate cancer than parental 34-mer; in the renal cell carcinoma, P18 strongly decreased angiogenesis and halted the progression of established tumors. Conclusions: P18 is a novel and potent antiangiogenic biotherapeutic agent that has potential to be developed for the treatment of prostate and renal cancer.Angiogenesis (the formation of new capillaries from established ones) is a necessary prerequisite for the exponential tumor growth. Angiogenesis is regulated by the balance between positive and negative regulators, inhibitors and stimuli, in the tumor microenvironment also termed angiogenic switch: in the normal tissue, the prevalence of inhibitors maintains vascular quiescence, whereas, in tumors, the balance is tipped in favor of the stimuli (1). Angiogenic switch can be flipped back to the ''off position'' by sequestering angiogenic stimuli with appropriate neutralizing antibodies, by blocking their signaling receptors using small-molecule inhibitors, or by employing natural antiangiogenic molecules. The advent of therapies targeting proangiogenic vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB or their receptors (Avastin, sunitinib, and sorafenib; refs. 2,3) underscores the therapeutic value of antiangiogenics but also highlights the possibility of overcoming the withdrawal of a single angiogenic factor (4). Studies of past two decades suggest that natural inhibitors of angiogenesis act as endothelial-specific tumor suppressors (5); their specificity for remodeling endothelium...
Background: Thoracic disc herniation accounts for only 0.15 to 1.8% of all spinal herniated discs. Usually present between the third and sixth decades with a female predilection. Objectives: To describe the surgical outcome and prognostic factors of post-decompression without fixation in CTDs. Patient and methods: from October 2016 to July 2019, a series of 9 patients with a CTD with demographic data, presentation, imaging findings, operative details, degree of spinal stenosis, duration of symptoms `and outcomes using ASIA scale or mFAC. Results: All patients presented with at least one sign of myelopathy. Simple laminectomy was performed, and followup was in 1st week and 6th month. In 1st week, according to ASIA grade improved in 4 (44, 4%), stationary in 3 (33.3%), deteriorated in 2 (22.2%) patients. According to ambulation, non-ambulatory in 3 (33.3%) and independent in 5 (66.6%) patients. In 6th month, according to ASIA grade improved in 5 (62.5%), stationary in 2 (25%), deteriorated in1 (12.5%) patient. According to ambulation, non-ambulatory in 1 (12.5%), independent in 3 (37.5%) and walker in 4 (50%) patients, one patient is missed in the 6th-month follow-up. Prognostic factors affected the surgical outcome, including the degree of spinal canal stenosis and duration of symptoms. Conclusions: Posterior decompression without instrumentation allowed us to decompress the compromised spinal cord. Results overall are good with the majority of patients improving at least 1 ASIA scale or mFAC. Better outcomes were affected with less degree of spinal stenosis and less duration of symptoms
Background: Atypical meningiomas differ from Grade I meningiomas in aspects of the higher rate of recurrence, more postoperative complications, and shorter life expectancy postoperatively. Objective: This study was aimed to evaluate the clinical course of atypical meningioma and prognostic factors affecting its surgical outcomes. Patients and Method: This retrospective study investigated the medical records of 45 patients who had surgical removal of atypical meningiomas at Benha University Hospitals between January 2010 and December 2021. Patients average age was (56.69± 11.11) ranged from 29 to 74 years. The follow-up period was 60 months. Analysis included multiple factors such as patient age, gender, tumor size, location, and the extent of surgical resection based on (Simpson Grading System). Results: There was significant relationship between recurrence and Simpson grade, size, and side. There was a significant relationship between rate of recurrence and type of radiation used. The mean survival time was significantly longer in Gamma knife group compared to radiotherapy. Rate of mortality was significantly higher in group radiotherapy compared to gamma knife with hazard ratio (95% CI) (5.33(0.79-36.75%). Rate of recurrence was significantly higher in group radiotherapy compared to gamma knife with hazard ratio (95% CI) (3.03(0.89-10.31%). Conclusion:It could be concluded that atypical meningiomas in elderly patients with a large size especially more than 60cc, incomplete surgical resection; frequently have poorer prognosis following surgical intervention. Postoperative radiotherapy could provide accepted local tumor control in patients with incompletely resected atypical meningioma.
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