scholarly journals The dual inhibitor of the phosphoinositol-3 and PIM kinases, IBL-202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment

2018 ◽  
Vol 182 (5) ◽  
pp. 654-669 ◽  
Author(s):  
Kyle Crassini ◽  
Yandong Shen ◽  
Michael O'Dwyer ◽  
Michael O'Neill ◽  
Richard Christopherson ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Tumour Microenvironment ◽  
Dual Inhibitor ◽  
Pim Kinases

scholarly journals Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases

2019 ◽  
Vol 12 (2) ◽  
pp. 69 ◽  
Author(s):  
Daniel A. Rodrigues ◽  
Fernanda S. Sagrillo ◽  
Carlos A. M. Fraga
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Chronic Lymphocytic Leukaemia ◽  
Drug Administration ◽  
Small Molecule ◽  
Lymphocytic Leukaemia ◽  
Food And Drug Administration ◽  
Small Lymphocytic Lymphoma ◽  
Dual Inhibitor ◽  
Systemic Therapies

Duvelisib (Copiktra®) is a dual inhibitor of phosphoinositide 3-kinases (PI3Kδ and PI3Kγ). In 2018, duvelisib was first approved by the Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma (SLL) after at least two prior therapies. Duvelisib has also been approved under accelerated track for relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. In this review, we provide a series of information about duvelisib, such as the development of clinical trials for LLC/SLL and FL and the steps used for its synthesis.

scholarly journals Microenvironment‐induced PIM kinases promote CXCR 4‐triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration

2018 ◽  
Vol 22 (7) ◽  
pp. 3548-3559 ◽  
Author(s):  
Emilia Białopiotrowicz ◽  
Patryk Górniak ◽  
Monika Noyszewska‐Kania ◽  
Bartosz Puła ◽  
Hanna Makuch‐Łasica ◽  
...  
Keyword(s):  
Cell Migration ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Mtor Pathway ◽  
Leukaemia Cell ◽  
Pim Kinases ◽  
Chronic Lymphocytic Leukaemia Cell

scholarly journals Protoporphyrin IX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and induces apoptosis in B-cell chronic lymphocytic leukaemia cells

2019 ◽  
Author(s):  
Liren Jiang ◽  
Natasha Malik ◽  
Pilar Acedo ◽  
Joanna Zawacka-Pankau
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Lymphocytic Leukaemia ◽  
Aminolevulinic Acid ◽  
Tumor Regression ◽  
Protoporphyrin Ix ◽  
Photodynamic Diagnosis ◽  
Dual Inhibitor ◽  
Normal Cells ◽  
Cell Chronic Lymphocytic Leukaemia

Abstractp53 is a tumor suppressor, which belongs to the p53 family of proteins. The family consists of p53, p63 and p73 proteins, which share similar structure and function. Activation of wild-type p53 or TAp73 in tumors leads to tumor regression, and small molecules restoring the p53 pathway are in clinical development.Protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid, is a clinically approved drug applied in photodynamic diagnosis and therapy. PpIX induces p53- and TAp73-dependent apoptosis and inhibits TAp73/MDM2 and TAp73/MDM4 interactions. Here we demonstrate that PpIX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and activates apoptosis in B-cell chronic lymphocytic leukaemia cells without illumination and without affecting normal cells. PpIX stabilizes p53 and TAp73 proteins, induces p53-downstream apoptotic targets and provokes cancer cell death at doses non-toxic to normal cells.Our findings open up new opportunities for repurposing PpIX for treating lymphoblastic leukaemias withwtTP53.

scholarly journals A Boolean Model of the Formation of Tumour Associated Macrophages in an in-vitro Model of Chronic Lymphocytic Leukaemia

2020 ◽  
Author(s):  
Malvina Marku ◽  
Flavien Raynal ◽  
Nina Verstraete ◽  
Marcin Domagala ◽  
Miguel Madrid-Mencía ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Cancer Cells ◽  
Lymphocytic Leukaemia ◽  
Tumour Progression ◽  
Macrophage Polarization ◽  
Tumour Microenvironment ◽  
Boolean Model ◽  
Specific Receptors ◽  
Vitro Model

AbstractThe tumour microenvironment is the collection of cells in and surrounding cancer cells in a tumour including a variety of immune cells, especially neutrophils and monocyte-derived macrophages. In a tumour setting, macrophages encompass a spectrum between a tumour-suppressive (M1) or tumour-promoting (M2) state. The biology of macrophages found in tumours (Tumour Associated Macrophages) remains unclear, but understanding their impact on tumour progression is highly important. In this paper, we perform a comprehensive analysis of a macrophage polarization network, following two lines of enquiry: (i) we reconstruct the macrophage polarization network based on literature, extending it to include important stimuli in a tumour setting, and (ii) we build a dynamical model able to reproduce macrophage polarization in the presence of different stimuli, including the contact with cancer cells. Our simulations recapitulate the documented macrophage phenotypes and their dependencies on specific receptors and transcription factors, while also elucidating the formation of a special type of tumour associated macrophages in an in-vitro model of chronic lymphocytic leukaemia. This model constitutes the first step towards elucidating the cross-talk between immune and cancer cells inside tumours, with the ultimate goal of identifying new therapeutic targets that could control the formation of tumour associated macrophages in patients.

Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia

2000 ◽  
Vol 111 (1) ◽  
pp. 230-238 ◽  
Author(s):  
Mohammad Reza Rezvany ◽  
Mahmood Jeddi-Tehrani ◽  
Hodjattallah Rabbani ◽  
Ulla Ruden ◽  
Lennart Hammarstrom ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Lymphocytic Leukaemia ◽  
Cell Chronic Lymphocytic Leukaemia ◽  
Cdr3 Region

Pharmacokinetics of Chlorambucil in Patients with Chronic Lymphocytic Leukaemia: Comparison of Different Days, Cycles and Doses

2000 ◽  
Vol 87 (5) ◽  
pp. 223-228 ◽  
Author(s):  
Raija Silvennoinen ◽  
Kimmo Malminiemi ◽  
Outi Malminiemi ◽  
Erkki Seppala ◽  
Juhani Vilpo
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia
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