The co-carcinogenic effect of topical vitamin A palmitate on 9, 10-dimethyl-1, 2-benzathracene (DMBA)-induced carcinoma in the buccal pouch of the syrian golden hamster

Salley in 1954, (122) was the first worker to use the hamster cheek pouch as a model for experimental carcinogenesis and to produce squamous cell carcinomas in this organ. For a number of reasons, the pouch is most suitable for sequential studies of carcinogenesis, and these include the fact that it is easily accessible and can be everted simply, facilitating macroscopic examination. Furthermore, its anatomic situation makes it a simple model for topical application of any carcinogen. Each animal has two pouches, thus providing its own control. In addition, the pouch serves as a storehouse and is lined only by stratified squamous epithelium with no glands or hair follicles in its wall, thus rendering it less susceptible to cyclic changes than more complex tissues, in which accessory structures are present

Absolute monocyte count and lymphocyte-monocyte ratio predict outcome in nodular sclerosis Hodgkin lymphoma: Evaluation based on data from 1450 patients

Objective: To verify whether absolute monocyte count (AMC) and lymphocyte-monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL). Patients and Methods: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007. Results: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm3, and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; P<.001). The overall survival (OS) at 10 years for an AMC of more than 750 cells/mm3 was 78% (70%-85%), and the OS at 10 years for an AMC of 750 cells/mm(3) or less was 88% (84%-90%; P=.01). In multivariate analysis, both AMC and LMR maintained prognostic significance for PFS (hazard ratio [HR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3). Conclusion: This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice

Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option

Ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients. More recently, data from the phase III ALPINE trial, which directly compared zanu with ibrutinib, demonstrated that zanu’s advantages include an improved safety profile as well as enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and the most recent German CLL algorithm suggest that zanu may replace first-generation BTKis as a preferred therapeutic option for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile. Some drug class-related characteristics such as drug resistance, low complete remission (CR) rates, and indefinite treatment duration still remain with zanu, and the results from recently completed and ongoing fixed-duration clinical trials, combining zanu with an anti-BCL2 agent, are eagerly awaited with the possible promise of a reduced treatment duration and lower financial burden

Phorbol Ester (TPA)-Induced Surface Membrane Alterations in B-Type Hairy Cell and Lymphocytic Leukemia Cells

This report documents phorbol ester (TPA)-induced changes in cell morphology, and in vitro growth patterns in 9 patients with hairy cell leukemia (HCL), 21 with B-type CLL and non-Hodgkin\u27s lymphoma in leukemic phase (NHL), and 10 with acute non lymphoblastic leukemia (ANLL). TPA caused cells from HCL to adhere strongly and produce elongated cytoplasmic extensions. Many of these cells had an appearance resembling fibroblasts, while others showed marked surface ruffling and spreading containing increased dense bodies, and phagolysosomal vacuoles as seen by transmission electron microscopy. This HCL in vitro growth pattern after TPA exposure differed from that seen in B-CLL and NHL cells, which only adhered moderately after 72 hours and readily detached in clumps. CLL and NHL-cells did not show ultrastructural features of macrophages but had either plasmacytic or HCL features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias. The expression of surface markers, tartrate resistant acid phosphatase (TRAP) and Ig secretion were studied in some B-CLL, NHL and HCL cells after exposure to different concentrations of TPA for up to 6 days. Results showed that the documented changes were frequently both dose and time dependent and the most striking HCL-features were encountered after 6 days incubation with higher concentrations of TPA. However, individual variation from case to case was noted. Nevertheless, it seems that TPA induces neoplastic B-cells to mature into secreting plasmacytoid lymphocytes, and cells with features of HCL with variable expression of surface markers and TRAP

Topical Modes in the Preparation of Human Spleen Specimens for Routine Scanning Electron Microscopy Studies

Various preparatory techniques were used to improve scanning electron microscopy images of the fine structure of vascular, cellular, and cordal-reticular components of normal human spleens. The progressive method of fixation (GTGO) applied in the present study, allowed air drying of the tissues and rendered the specimens conductive even in newly fractured surfaces. Vascular perfusion proved necessary only in studies of the splenic blood vessels, while a simple immersion of tissue blocks in the washing solution resulted in better images of the white pulps. Interstitial (trans-splenic) perfusion was found to be superior to vascular perfusion for routine preparation of spleen tissues, and freeze-cracking did not necessarily lead to improved images of the specimen\u27s surfaces. Combined with proper washing and shaping protocols, the GTGO procedure is shown to be a superior mode of specimen preparation, abolishing most traditional artifacts and obtaining clear images of the complex splenic tissue

Exploring factors influencing low back pain in people with non-dysvascular lower limb amputation: a national survey

Background: Chronic low back pain (LBP) is a common musculoskeletal impairment in people with lower limb amputation. Given the multifactorial nature of LBP, exploring the factors influencing the presence and intensity of LBP is warranted. Objective: To investigate which physical, personal, and amputee-specific factors predicted presence and intensity of low back pain (LBP) in persons with non-dysvascular transfemoral (TFA) and transtibial amputation (TTA). Design: A retrospective cross-sectional survey. Setting: A national random sample of people with non-dysvascular TFA and TTA. Participants: Participants (N = 526) with unilateral TFA and TTA due to non-dysvascular aetiology (i.e. trauma, tumours, and congenital causes) and a minimum prosthesis usage of one year since amputation were invited to participate in the survey. The data from 208 participants (43.4% response rate) were used for multivariate regression analysis Methods (Independent variables): Personal (i.e. age, body mass, gender, work status, and presence of comorbid conditions), amputee-specific (i.e. level of amputation, years of prosthesis use, presence of phantom limb pain, residual limb problems, and non-amputated limb pain), and physical factors (i.e. pain provoking postures including standing, bending, lifting, walking,sitting, sit-to stand, and climbing stairs). Main outcome measures (Dependent variables): LBP presence and intensity. Results: A multivariate logistic regression model showed that the presence of two or more comorbid conditions (prevalence odds ratio (POR) = 4.34, p = .01), residual limb problems (POR 22 = 3.76, p<.01), and phantom limb pain (POR = 2.46, p = .01) influenced the presence of LBP. Given the high LBP prevalence (63%) in the study, there is a tendency for overestimation of PORand the results must be interpreted with caution. In those with LBP, the presence of residual limb problems (beta = 0.21, p = .01), and experiencing LBP symptoms during sit-to-stand task (beta = 0.22, p = .03) were positively associated with LBP intensity, while being employed demonstrated a negative association (beta = - 0.18, p = .03) in the multivariate linear regression model. Conclusions: Rehabilitation professionals should be cognisant of the influence that comorbid conditions, residual limb problems, and phantom pain have on the presence of LBP in people with non-dysvascular lower limb amputation. Further prospective studies could investigate the underlying causal mechanisms of LBP