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

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

Adhesion, Spreading and Fragmentation of Human Megakaryocytes Exposed to Subendothelial Extracellular Matrix: A Scanning Electron Microscopy Study

Platelet agonists and subendothelial extra-cellular matrix (ECM) induce morphological and biochemical changes in animal megakaryocytes, reminiscent of the response of platelets to the same substances. We have examined the behavior of human megakaryocytes exposed for up to 36 hours to the ECM produced by cultured bovine corneal endothelial cells. By phase contrast and scanning electron microscopy these megakaryocytes demonstrated non-reversible adherence and flattening with formation of long filopodia, thus confirming that human megakaryocytes acquire platelet functional capacities. In addition, megakaryocyte fragmentation into prospective platelets was apparently induced by the ECM. Up to 50% of the adherent megakaryocytes underwent spontaneous fragmentation into small particles which individually reacted like platelets on the ECM. The interaction of the megakaryocytes with the ECM was specific since no adherence, flattening or fragmentation occured upon incubation of the megakaryocytes on regular tissue culture plastic or glutaraldehyde fixed ECM. Thus we have demonstrated platelet like behaviour of human megakaryocytes in response to this physiological basement membrane and a possible role of the subendothelium in platelet production which may occur in vivo as megakaryocytes cross the sinusoid walls and enter the blood stream