In 1918 German troops occupied the territory of Ukraine. They came to a halt in the western parts of the Don Cossack Republic. German occupation policy between various parties, mostly of them ...anti-Bolshevik and preparing for campaigns against the Red Army, was friendly and favourable towards the Cossacks, though officially neutral. The most eastern vanguard of German imperialism tried to evade any closer involvement into local affairs, but became confronted with a naval assault by Red troops from the opposite coast of the Sea of Asov. There, in the town of Eysk, a local Soviet power launched a broad attack against the occupants in their unguarded rear near Taganrog. The German command acted quickly and put down the landing forces within three days. However, of some 10 000 enemies, over 2000 were killed after they had surrendered to the Germans. Owing to a sole order of the German combat commander, this was executed after the battle was over. Questioned by the higher German command, which feared interrogation and discussion by the German parliament, the commander evolved arguments for his decision, which were identic to such used in the notorious `Kommissarbefehl' 23 years later: the enemy was to be seen outside international law due to his methods of warfare. Inconspicuous as the incident passed through historical research and investigation by international law, it obviously had its effects: when in late 1918 the Germans marched home through eastern Ukraine, all the officers of a rearguard batallion were shot by a Bolshevik detachment, `in revenge for 8000 Bolsheviks' massacred at Taganrog half a year before. A radical change of paradigms in warfare seems to have occurred twice during that year. Against the background of this incident of action and reaction on the Bay of Mius (Miusskii liman) in 1918, atrocities on the Eastern front from the start of the Soviet-German war in 1941 on may be evaluated in a new light. Abstract printed by permission of Franz Steiner Verlag, Stuttgart, Germany
Chromosome instability (CIN) is defined as an increased rate of chromosome gains and losses that manifests as cell-to-cell karyotypic heterogeneity and drives cancer initiation and evolution. Current ...research efforts are aimed at identifying the etiological origins of CIN, establishing its roles in cancer pathogenesis, understanding its implications for patient prognosis, and developing novel therapeutics that are capable of exploiting CIN. Thus, the ability to accurately identify and evaluate CIN is critical within both research and clinical settings. Here, we provide an overview of quantitative single cell approaches that evaluate and resolve cell-to-cell heterogeneity and CIN, and discuss considerations when selecting the most appropriate approach to suit both research and clinical contexts.
High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy in women with a high level of mortality, metastatic disease, disease recurrence and multi-drug resistance. Many ...previous studies have focused on characterising genome instability in recurrent resistant HGSOC and while this has advanced our understanding of HGSOC, our fundamental knowledge of the mechanisms driving genome instability remains limited. Chromosome instability (CIN; an increased rate of chromosome gains and losses) is a form of genome instability that is commonly associated with recurrence and multi-drug resistance in many cancer types but has just begun to be characterised in HGSOC.
To examine the relationship between CIN and HGSOC, we employed single-cell quantitative imaging microscopy approaches capable of capturing the cell-to-cell heterogeneity associated with CIN, to assess the prevalence and dynamics of CIN within individual and patient-matched HGSOC ascites and solid tumour samples.
CIN occurs in 90.9% of ascites samples and 100% of solid tumours, while in-depth analyses identified statistically significant temporal dynamics within the serial ascites samples. In general, aneuploidy and CIN increase with disease progression and frequently decrease following chemotherapy treatments in responsive disease. Finally, our work identified higher levels of CIN in solid tumours relative to ascites samples isolated from the same individual, which identifies a novel difference existing between solid tumours and ascites samples.
Our findings provide novel insight into the relationship between CIN and HGSOC, and uncover a previously unknown relationship existing between CIN in solid tumours and metastatic disease (ascites).
•Chromosome instability (CIN) is prevalent and dynamic in high-grade serous ovarian cancer (HGSOC).•Quantitative imaging microscopy reveals 91% of ascites (26 samples) and 100% of solid tumours (36 samples) exhibit CIN.•CIN increases with disease progression and decreases following chemotherapy treatment.•Higher levels of CIN occur in solid tumour samples relative to patient-matched ascites samples.•Data suggest that cells with lower levels of CIN may be more amendable to metastatic spread.
The AGE inhibitor pyridoxamine inhibits lipemia and development of vascular and renal disease in Zucker obese rats.
In previous studies, pyridoxamine (PM) limited the formation of advanced glycation ...end products (AGEs) and development of nephropathy in streptozotocin-diabetic rats without affecting glycemic control. However, the lipid-lowering effects of PM and the correlation of plasma cholesterol and triglycerides with AGEs in skin collagen suggested that lipids might be an important source of AGEs in the diabetic rat. This study addresses the effects of hyperlipidemia on formation of advanced glycation and lipoxidation end products (AGE/ALEs) and the effects of PM on hyperlipidemia, hypertension, AGE/ALE formation, and development of nephropathy in the nondiabetic, Zucker obese rat.
Three groups of Zucker rats were studied: lean (Fa/fa), untreated fatty (fa/fa), and fa/fa treated with PM (2 g/L drinking water). Blood pressure, plasma lipids and creatinine, and urinary albumin were measured monthly. AGE/ALEs were measured in skin collagen by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Changes in wall thickness of the aorta and renal arterioles were evaluated by light microscopy.
AGE/ALEs formation was increased two- to threefold in skin collagen of obese versus lean rats. PM inhibited the increases in AGE/ALEs in collagen, and significantly decreased the rise in plasma triglycerides, cholesterol, and creatinine, corrected hypertension and thickening of the vascular wall, and nearly normalized urinary protein and albumin excretion in Zucker fa/fa rats.
Lipids are an important source of chemical modification of tissue proteins, even in the absence of hyperglycemia. PM inhibited AGE/ALE formation and hyperlipidemia and protected against renal and vascular pathology in a nondiabetic model.
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