Dendritic cells: making progress with tumour regression?

Due to their potent ability to activate the immune system, dendritic cells (DC) are showing promise as potential adjuvants for tumour immunotherapy of cancer patients. However, little is known about the effect tumour cells can have on DC function. Indeed, the discovery of different DC subsets with different immunological functions indicates that the relationship between tumour cells and tumour-infiltrating DC subtypes is likely to be complex. There remains a lot to be understood about the effects of tumours on DC before we can expect to benefit from DC-based tumour immunotherapy of cancer patients. Here we review the recent advances being made in understanding DC phenotype and function in relation to interactions with different types of tumours.     

Embryonic stem cells: are useful in clinic treatments?

It is not uncommon to find statements in the social media and even in some scientific journals declaring that embryonic stem cells can be used in human medicine for therapeutic purposes. In our opinion, this statement does not fit the medical reality. To go into this subject in depth, and if possible to clarify it, we reviewed the most recent literature on clinical trials conducted with embryonic stem cells, concluding that up to the present time, there is only one ongoing clinical trial being carried out with these types of cells to treat a small group of patients with spinal cord injury. The results of this trial have still not been published. In conclusion, at present, there is only evidence of one phase I clinical trial conducted with embryonic stem cells, in comparison to the numerous trials conducted with adult stem cells.     

Macrophage fusion: are somatic and cancer cells possible partners?

Macrophages are present in all tissues and can fuse with themselves to differentiate into multinucleate osteoclasts or giant cells that play a central role in osteoporosis and chronic inflammatory diseases, respectively. Yet, the mechanism by which they fuse remains uncharacterized. The macrophage fusion receptor (MFR) and its ligand CD47 might mediate homotypic fusion of macrophages and allow for their recognition as 'self' before fusion. Although a novel process and controversial idea, macrophages might exploit a similar mechanism for fusion with somatic cells or tumor cells, with resultant organ repair or metastasis, respectively. Hence, macrophages might be the 'double-edged swords' of tissues.     

Macrophage fusion: are somatic and cancer cells possible partners?

The fusion of cells is a fundamental biological event that plays a central role in a variety of developmental and homeostatic processes. Macrophages are present in all tissues and can initiate interaction and fusion. The putative macrophage-fusion machinery is still poorly understood, but some of its components have been identified. Macrophages recognize each other as < self > in order to fuse but some essential questions remain: do macrophages fuse with somatic cells to repair tissues and organs? Do macrophages fuse with tumor cells to trigger metastasis? Agnès Vignery discusses these novel and challenging ideas in this review.     

Towards a blood-stage vaccine for malaria: are we following all the leads?

Although the malaria parasite was discovered more than 120 years ago, it is only during the past 20 years, following the cloning of malaria genes, that we have been able to think rationally about vaccine design and development. Effective vaccines for malaria could interrupt the life cycle of the parasite at different stages in the human host or in the mosquito. The purpose of this review is to outline the challenges we face in developing a vaccine that will limit growth of the parasite during the stage within red blood cells--the stage responsible for all the symptoms and pathology of malaria. More than 15 vaccine trials have either been completed or are in progress, and many more are planned. Success in current trials could lead to a vaccine capable of saving more than 2 million lives per year.     

The stem cells of small intestinal crypts: where are they?

Recently, there has been resurgence of interest in the question of small intestinal stem cells, their precise location and numbers in the crypts. In this article, we attempt to re-assess the data, including historical information often omitted in recent studies on the subject. The conclusion we draw is that the evidence supports the concept that active murine small intestinal stem cells in steady state are few in number and are proliferative. There are two evolving, but divergent views on their location (which may be more related to scope of capability and reversibility than to location) several lineage labelling and stem cell self-renewing studies (based on Lgr5 expression) suggest a location intercalated between the Paneth cells (crypt base columnar cells (CBCCs)), or classical cell kinetic, label-retention and radiobiological evidence plus other recent studies, pointing to a location four cell positions luminally from the base of the crypt The latter is supported by recent lineage labelling of Bmi-1-expressing cells and by studies on expression of Wip-1 phosphatase. The situation in the human small intestine remains unclear, but recent mtDNA mutation studies suggest that the stem cells in humans are also located above the Paneth cell zone. There could be a distinct and as yet undiscovered relationship between these observed traits, with stem cell properties both in cells of the crypt base and those at cell position 4.     

Kidney atrophy vs hypertrophy in diabetes: which cells are involved?

One of the first structural changes in diabetic nephropathy (DN) is the renal enlargement. These changes resulted in renal hypertrophy in both glomerular and tubular cells. Shrink in the kidney size, which described as kidney atrophy resulted from the loss of nephrons or abnormal nephron function and lead to loss of the kidney function. On the other hand, increase in kidney size, which described as hypertrophy resulted from increase in proximal tubular epithelial and glomerular cells size. However overtime, tubular atrophy and tubulointerstitial fibrosis occurs as subsequent changes in tubular cell hypertrophy, which is associated with the infiltration of fibroblast cells into the tubulointerstitial space. The rate of deterioration of kidney function shows a strong correlation with the degree of tubulointerstitial fibrosis. A consequence of long-standing diabetes/hyperglycemia may lead to major changes in renal structure that occur but not specific only to nephropathy. Identifying type of cells that involves in renal atrophy and hypertrophy may help to find a therapeutic target to treat diabetic nephropathy. In summary, the early changes in diabetic kidney are mainly includes the increase in tubular basement membrane thickening which lead to renal hypertrophy. On the other hand, only renal tubule is subjected to apoptosis, which is one of the characteristic morphologic changes in diabetic kidney to form tubular atrophy at the late stage of diabetes.     

Small molecule compounds targeting the p53 pathway: are we finally making progress?

Loss of function of p53, either through mutations in the gene or through mutations to other members of the pathway that inactivate wild-type p53, remains a critically important aspect of human cancer development. As such, p53 remains the most commonly mutated gene in human cancer. For these reasons, pharmacologic activation of the p53 pathway has been a highly sought after, yet unachieved goal in developmental therapeutics. Recently progress has been made not only in the discovery of small molecules that target wild-type and mutant p53, but also in the initiation and completion of the first in-human clinical trials for several of these drugs. Here, we review the current literature of drugs that target wild-type and mutant p53 with a focus on small-molecule type compounds. We discuss common means of drug discovery and group them according to their common mechanisms of action. Lastly, we review the current status of the various drugs in the development process and identify newer areas of p53 tumor biology that may prove therapeutically useful.     

Radial glial cells. are they really glia?

During the development of the cerebral cortex, radial glia serve as a scaffold to support and direct neurons during their migration. This view is now changing in the light of emerging evidence showing that these cells have a much more dynamic and diverse role. A recent series of studies has provided strong support for their role as precursor cells in the ventricular zone that generate cortical neurons and glia, in addition to providing migration guidance.     

Anaesthesia and post-operative analgesia following experimental surgery in laboratory rodents: are we making progress?

Current attitudes to the use of animals in biomedical research require that any pain or distress should be minimised. This can often be achieved by the use of appropriate anaesthetic and analgesic regimens. There, is however, little information on the peri-operative regimens used. A literature review was conducted to estimate how commonly analgesics are administered to laboratory rodents, the most widely used species of laboratory animals, and to assess the anaesthetic regimens employed. Studies describing potentially painful experimental procedures involving rodents were identified from peer-reviewed journals published from 1990 to 1992 and from 2000 to 2002. In papers published between 2000 and 2002, if analgesic administration was not specified, the institutional veterinary surgeons or authors of the papers were contacted by e-mail to obtain additional information on analgesic use. From 1992 to 2002, there was an increase in the reported prevalence of analgesic administration to laboratory rodents from 2.7% to 19.8%. Although the use of analgesics has increased over the past ten years, the overall level of post-operative pain relief for laboratory rodents is still low. Anaesthetic methodology changed markedly between the two time-periods sampled. Notably, there was an increase in the use of isoflurane and of injectable anaesthetic combinations such as ketamine/xylazine, whereas the use of ether and methoxyflurane decreased.     

Why are dendritic cells central to cancer immunotherapy?

Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable alternative to radiation or chemotherapy in the treatment of cancer. The resurgence of interest in cancer immunotherapy reflects the promising results that have been obtained in both animal models and early clinical trials with the DC-based approach. Here I suggest that this optimism is justified because the efficient capture and presentation of antigens by DCs is central to the induction of an immune response. I argue that the mechanism by which DCs capture antigen suggests that the immune system might actually be 'blind' to tumours, thereby challenging the theory of immune surveillance.