Pathology and genetics of tumors of soft tissue and bone

Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.

http://science.sciencemag.org/content/sci/328/5986/1662.full.pdf

Reconstituting Organ-Level Lung Functions on a Chip

/pdf/pathology-and-genetics-of-tumours-of-the-digestive-system-3xy9cwrc3c.pdf

Pathology and genetics of tumours of the digestive system

Background Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stag...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a “receptive substance,” from which the idea of a “receptor” came to light. Subsequent studies...

/pdf/mammalian-nicotinic-acetylcholine-receptors-from-structure-1woeprh7qg.pdf

Mammalian nicotinic acetylcholine receptors: from structure to function.

https://www.rima.org/web/medline_pdf/LiverTranspl2006Aug1281260-7.pdf

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma

Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—what limits limited disease?

The non-neuronal cholinergic system in humans: expression, function and pathophysiology.

https://www.jstage.jst.go.jp/article/jjp/85/1/85_1_2/_pdf

The Non-neuronal Cholinergic System

Sepsis is a frequent complication of multiple organ dysfunction syndrome and remains a major problem of intensive care medicine. It is also a common factor in the final cause of death in hospital populations. Clinical observations, assisted by invasive monitoring techniques as well as pathological-anatomical studies, clearly indicate that microcirculatory dysfunction lies at the centre of sepsis pathogenesis. Numerous animal models, from rodents to primates, many of which employ bacteria or their toxins, especially endotoxins, have helped to shed light on the pathomechanisms leading to this dysregulation in the peripheral circulation. Among these are activation of humoral and cellular inflammatory mediator systems, with special emphasis on neutrophil-endothelial interactions, affecting endothelial barrier function and vasoregulation and ultimately leading to severely perturbed oxygen transport and utilization. In vitro studies have provided more insight into the molecular mechanisms involved in this microcirculatory dysfunction, although much more attention must be directed towards microvascular endothelial cells and the role of heterogeneity of response in various vascular beds. These experimental data must in turn be validated by comparing with the human in situ situation, both clinical and morphological. This review aims at a critical appraisal of the clinical and experimental evidence for sepsis-induced dysregulation of the microcirculation and how knowledge of the underlying cellular and molecular pathology could be used to make therapy more rational and effective. To date, therapeutic approaches, such as anti-cytokine and anti-oxidant regimens, which have been highly successful in experimental models, have failed to demonstrate clinical efficacy. Newer approaches, such as targeting the coagulation system, nitric oxide synthesis or intracellular signal transduction, are also discussed. The necessity to focus on the role of anti-inflammatory mediators, as well as the pathogenetic significance of important molecular groups, such as the heat shock proteins, which until now have been given scant attention, will be stressed.

Fernando Bittinger

Papers

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma

Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—what limits limited disease?

The non-neuronal cholinergic system in humans: expression, function and pathophysiology.

The Non-neuronal Cholinergic System

Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy?