Metabolic reprogramming, malignant transformation and metastasis: lessons from chronic lymphocytic leukaemia and prostate cancer.

Metabolic reprogramming is a hallmark of cancer, crucial for malignant transformation and metastasis. Chronic lymphocytic leukaemia (CLL) and prostate cancer exhibit similar metabolic adaptations, particularly in glucose and lipid metabolism. Understanding this metabolic plasticity is crucial for identifying mechanisms contributing to metastasis.

Synthesis and Biochemical Evaluation of Ethanoanthracenes and Related Compounds: Antiproliferative and Pro-Apoptotic Effects in Chronic Lymphocytic Leukemia (CLL).

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells, and it is the most frequent form of leukemia diagnosed in Western countries. It is characterized by the proliferation and accumulation of neoplastic B lymphocytes in the blood, lymph nodes, bone marrow and spleen. We report the synthesis and antiproliferative effects of a series of novel ethanoanthracene compounds in CLL cell lines.

Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt's Lymphoma (BL).

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of ()-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt's lymphoma (BL) cell lines, a rare form of non-Hodgkin's immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL.

Isolation and Cryopreservation of Mononuclear Cells from Peripheral Blood and Bone Marrow of Blood Cancer Patients.

Peripheral blood and bone marrow aspirates are routinely obtained from blood cancer patients for diagnostic investigations and provide an accessible source of patient-specific cancer cells, as well as non-malignant cells, for research proposes. The simple and reproducible method presented here allows isolation of viable mononuclear cells, including malignant cells, from fresh peripheral blood or bone marrow aspirates using density gradient centrifugation. The cells obtained using the protocol described can be further purified for a variety of cellular, immunological, molecular, and functional assays.

Low CD49d expression in newly diagnosed chronic lymphocytic leukaemia may be associated with high-risk features and reduced treatment-free-intervals.

This study was carried out to assess the prognostic power of low CD49d expression (≥10%) in newly diagnosed CLL patients using a previously described cohort. Eighty-five patients were included. Median age at diagnosis; 70 years (43-88); CD49d was expressed in 33/85 (38.

A novel aryl-guanidinium derivative, VP79s, targets the signal transducer and activator of transcription 3 signaling pathway, downregulates myeloid cell leukaemia-1 and exhibits preclinical activity against multiple myeloma.

Aims: We have recently described a novel guanidinium-based compound, VP79s, which induces cytotoxicity in various cancer cell lines. Here, we aim to investigate the activity of VP79s and associated mechanisms of action in multiple myeloma (MM) cells in vitro and ex vivo.

Main Methods: The effects of VP79s on cell viability and induction of apoptosis was examined in a panel of drug-sensitive and drug-resistant MM cell lines, as well as ex vivo patient samples and normal donor lymphocytes and platelets.

Exploring the Anti-Cancer Mechanism of Novel 3,4'-Substituted Diaryl Guanidinium Derivatives.

We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e.

Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8 invariant natural killer T cells.

Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL).

BRAF V600E-Negative Hairy Cell Leukaemia.

Since the initial report of the BRAF V600E mutation in hairy cell leukemia, numerous investigators have demonstrated the presence of this activating mutation in nearly all cases of this disease. A case of hairy cell leukemia is documented with a classical clinical, morphological, immunophenotypic, and cytochemical profile in which the BRAF V600E was not detected. The diagnostic and therapeutic implications are discussed.

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells.

Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells.

Incidence of the BRAF V600E mutation in chronic lymphocytic leukaemia and prolymphocytic leukaemia.

The spectrum of underlying molecular abnormalities of clinically and biologically heterogeneous chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL) has yet to be identified. While whole genome sequencing has identified several genes implicated in the pathogenesis and progression of CLL, the molecular lesions in a substantial proportion of patients remain to be elucidated. The incidence of the BRAF V600E mutation, widely implicated in solid tumours and other B-cell malignancies, was sought in a cohort of patients with CLL and related disorders.

Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro.

Background: We proposed to investigate the radiosensitizing properties of PBOX-15, a novel microtubule-disrupting agent, in a panel of cancer cell lines.

Results: PBOX-15 treatment was associated with significant cell kill and increased radiosensitivity in all three cell lines tested. The number of surviving cells in response to the combined treatment was significantly less than PBOX -15 alone in 22Rv1 cells.

The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance.

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4.

The novel tubulin-targeting agent pyrrolo-1,5-benzoxazepine-15 induces apoptosis in poor prognostic subgroups of chronic lymphocytic leukemia.

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL.

A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin.

The ordered, directional migration of T-lymphocytes is a key process during immune surveillance, immune response, and development. A novel series of pyrrolo-1,5-benzoxazepines have been shown to potently induce apoptosis in variety of human chemotherapy resistant cancer cell lines, indicating their potential in the treatment of both solid tumors and tumors derived from the hemopoietic system. Pyrrolobenzoxazepine 4-acetoxy-5-(1-naphtyl)naphtho[2,3-b]pyrrolo[1,2-d][1,4]-oxazepine (PBOX-15) has been shown to depolymerize tubulin in vitro and in the MCF7 breast cancer cell line.