We have studied the mechanism by which lysosomotropic detergents kill baby hamster kidney cells. Lysosomotropic detergents are lysosomotropic amines (compounds with pK between 5 and 9, such as imidazole or morpholine) containing straight-chain hydrocarbon "tails" of 9-14 carbon atoms (Firestone, R. A., J. M. Pisano, and R. J. Bonney. 1979, J. Med. Chem., 22:1130-1133). Using lucifer yellow CH a...

Abstract Bispecific T-cell engagers (BiTEs) redirect endogenous populations to cells expressing tumour associated antigens induce cell killing. This inherently relies upon a cytotoxic population that is able be recruited. In many cancers, immune checkpoints and other immunosuppressive factors in the microenvironment lead of anergic T-cells which cannot redirected killing thus impede efficacy Bi...

Cervical cancer is a malignant transformation of keratinocytes initiated by the E7 oncoprotein of human papillomavirus (HPV). These tumors are characterized by keratinocyte hyperproliferation and are often infiltrated with activated CD8 T cells. HPV infection confers changes to gain immunological advantage to promote chronic infection, and these persist with malignant transformation. We investi...

Despite the continued importance of tuberculosis as a world-wide threat to public health, little is known about the mechanisms used by human lymphocytes to contain and kill the intracellular pathogen Mycobacterium tuberculosis. We previously described an in vitro model of infection of human monocytes (MN) with virulent M. tuberculosis strain H37Rv in which the ability of peripheral blood lympho...

Computer simulations of bacterial transformation are used to show that, under a wide range of biologically reasonable assumptions, transforming populations undergoing deleterious mutation and selection have a higher mean fitness at equilibrium than asexual populations. The source of transforming DNA, the amount of DNA taken up by each transforming cell, and the relationship between number of mu...

By representing damage induction by ionising particles and its repair by the cell, the probabilistic two-stage model provides a detailed description of the main processes involved in cell killing by radiation. To link this model with issues of interest in hadron radiotherapy, a simple Bragg peak model is used. Energy-loss, its straggling and the attenuation of the primary particle fluence are r...

Radiobiological models, such as the lethal and potentially lethal (LPL) model and the repair-misrepair (RMR) model, have been reasonably successful at explaining the cell killing effects of radiation. However, the models have been less successful at relating cell killing to the formation, repair and misrepair of double-strand breaks (DSBs), which are widely accepted as the main type of DNA dama...