Clinical Significance of BCL2, C-MYC, and BCL6 Genetic Abnormalities, Epstein-Barr Virus Infection, CD5 Protein Expression, Germinal Center B Cell/Non-Germinal Center B-Cell Subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 Proteins in Diffuse Large B-Cell Lymphoma : A Clinical and Pathological Correlation Study of 120 Patients

Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion: c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements

Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain

Specimen Shrinkage and Its Influence on Margin Assessment in Breast Cancer

The determination of tumour-free margin in breast cancer is crucial in deciding subsequent patient management. To exemplify the phenomenon of margin contraction during specimen preparation for histopathological analysis, we quantified the shrinkage of breast specimens as a result of formalin fixation. Methods: Fifty consecutive mastectomy and wide excision specimens were prospectively appraised. The closest free margin and maximal tumour diameter of fresh, unprepared specimens were recorded. These measurements were compared with the corresponding parameters following tissue fixation. Results: Following formalin fixation, the mean closest free margin of the specimens was found to have decreased from 10.28 mm to 6.78 mm (34%). The reduction of the mean diameter of the tumour itself was less significant, from 41.74 mm to 39.88 mm (4.5%). Conclusion: Breast specimens undergo shrinkage after histological fixation, losing more than a third of their original closest free margin, whilst the tumour itself does not shrink substantially. This phenomenon has vital implications in the accuracy of margin analysis and consequent decisions on further management, including re-operation and the institution of adjuvant radiotherapy

Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment?

Heat shock protein 27 (HSP27), induced by heat shock, environmental, and pathophysiological stressors, is a multi-functional protein that acts as a protein chaperone and an antioxidant. HSP27 plays a significant role in the inhibition of apoptosis and actin cytoskeletal remodeling. HSP27 is upregulated in many cancers and is associated with a poor prognosis, as well as treatment resistance, whereby cells are protected from therapeutic agents that normally induce apoptosis. This review highlights the most recent findings and role of HSP27 in cancer, as well as the strategies for using HSP27 inhibitors for therapeutic purposes

The Efficacy and Safety of ‘Inverted Omega En-bloc’ Holmium Laser Enucleation of the Prostate (HoLEP) for Benign Prostatic Hyperplasia: A Size-Independent Technique for the Surgical Treatment of LUTS

Purpose: To evaluate the safety, efficiency, and size-dependency of the ‘Inverted omega En-bloc (Ʊ)’ holmium laser enucleation of the prostate (HoLEP) in benign prostate hyperplasia (BPH) with lower urinary tract symptoms. Materials and Methods: A retrospective analysis of 716 consecutive patients who underwent HoLEP under the care of a single surgeon from 2014–2021. These patients were treated using the ‘Inverted omega En-bloc’ HoLEP technique for BPH. The patients were divided into 3 groups: Group 1 (<40 mL, n=328), Group 2 (40–60 mL, n=221), and Group 3 (≤60 mL, n=167). Perioperative parameters, safety, and functional outcomes were assessed and analyzed. Results: The perioperative parameters, like enucleation time (45.8±26.9 min), morcellation time (13.2±47.5 min), and catheterization duration (1.6±1.2 d) significantly differed to favor smaller prostate sizes (p<0.01). Significant improvements in the IPSS (total, voiding, storage, and quality of life), post-void residual urine, and maximum flow rate were observed 3 months post- HoLEP and continued during the 1-year follow-up period in all groups (p<0.01). The postoperative complications included urethral stricture in 11 patients (1.5%), bladder neck contracture in 12 (1.7%), urinary incontinence in 14 (2.0%), and bladder injuries in 4 (0.6%). Bladder neck contractures occurred only in Group 1. The postoperative surgical management for complications included urethral sounding (n=9, 1.3%), endoscopic internal urethrotomy (n=2, 0.3%), and re-HoLEP for bladder neck contractures in (n=12, 1.7%). The rate of re-HoLEP for regrowing adenomas was 15 (2.1%). Postoperative medications exceeding 6 months were α-blocker (n=22, 3.1%), cholinergics (n=16, 2.2%), anticholinergics (n=58, 8.1%), antidiuretics (n=18, 2.5%), and daily PDE5 inhibitor (n=38, 5.3%). Thirty-four patients (4.7%) had postoperative incidental prostate cancer. Conclusions: The inverted omega En-bloc HoLEP technique is safe and effective for the treatment of BPH. Moreover, ‘Inverted omega En-bloc’ HoLEP is a size-independent and effective method for all prostate sizes