Cancer stem cell hypothesis: a brief summary and two proposals

The investigation and development of the cancer stem cell (CSC) model has received much focus during these years. CSC is characterized as a small fraction of cancer cells that have an indefinite ability for self-renewal and pluripotency and are responsible for initiating and sustaining of the bulk of cancer. So, whether current treatment strategies, most of which target the rapid division of cancer cells, could interfere with the slow-cycling CSCs is broadly questioned. Meanwhile, however, the new understanding of tumorigenesis has led to the development of new drug screening strategies. Both stem cells and mesenchymal stem cells have been vigorously used in pre-clinical studies of their anti-tumor potential, mainly due to their inherent tumoritropic migratory properties and their ability to carry anti-tumor transgenes. Here, based on the tumorigenic and tumoritropic characteristics of CSCs, we proposed two hypotheses exploring possible usage of CSCs as novel anti-tumor agents and potential sources for tissue regeneration. Further experimental validation of these hypotheses may unravel some new research topics.     

Réflexions sur la place des médecins spécialistes en médecine nucléaire dans le dispositif d’annonce en cancérologie

Nuclear medicine physicians are very involved in French's oncology announcement procedure. However, their role needs to be analysed and evaluated. Before diagnosis’ announcement, information provided by nuclear medicine physicians are never neutral for patients. Information must not increase patient's anxiety or false patient's sense of reassurance. In this context, it seems necessary to engage in ethical reflexions about nuclear medicine physicians communication challenges.     

Inhibiting PHGDH with NCT-503 reroutes glucose-derived carbons into the TCA cycle,independently of its on-target effect

The small-molecule inhibitor of phosphoglycerate dehydrogenase, NCT-503, reduces incorporation of glucose-derived carbons into serine in vitro. Here we describe an off-target effect of NCT-503 in neuroblastoma cell lines expressing divergent phosphoglycerate dehydrogenase (PHGDH) levels and single-cell clones with CRISPR-Cas9-directed PHGDH knockout or their respective wildtype controls. NCT-503 treatment strongly reduced synthesis of glucose-derived citrate in all cell models investigated compared to the inactive drug control and independent of PHGDH expression level. Incorporation of glucose-derived carbons entering the TCA cycle via pyruvate carboxylase was enhanced by NCT-503 treatment. The activity of citrate synthase was not altered by NCT-503 treatment. We also detected no change in the thermal stabilisation of citrate synthase in cellular thermal shift assays from NCT-503-treated cells. Thus, the direct cause of the observed off-target effect remains enigmatic. Our findings highlight off-target potential within a metabolic assessment of carbon usage in cells treated with the small-molecule inhibitor, NCT-503.     

Trend (1999–2009) in U.S. death rates from myelodysplastic syndromes: Utility of multiple causes of death in surveillance

BackgroundFor myelodysplastic syndromes (MDS) (formerly known as preleukemia), a diverse group of myeloid neoplasms usually involving anemia in elderly persons, trends in U.S. death rates apparently have not been reported.MethodsTrends in annual age-standardized rates per 100,000 from 1999 to 2009 were examined for MDS using multiple causes vs. underlying cause alone, coded on death certificates for U.S. residents.ResultsThe death rate (all ages combined) for MDS increased from 1999 to 2009, from 1.62 to 1.84 using underlying cause alone and from 2.89 to 3.27 using multiple causes. Rates using multiple causes were about 80% higher than those based on underlying cause alone. From 2001 to 2004 the rate for MDS using underlying cause alone (but not using multiple causes) declined, accompanied by an increase in the rate for deaths from leukemia as underlying cause with mention of MDS; this trend coincided with the advent of the 2001 World Health Organization's reclassification of certain MDS as leukemia. The MDS rate for age 65+ years increased after 2005, whereas the rate for age 25–64 years was low but declined from 2001 to 2003 and then stabilized. For deaths with MDS coded as other than underlying cause, rates did not decline for deaths from each of the two most common causes (i.e., cardiovascular diseases and leukemia).ConclusionsEvidence for decreases in MDS-related mortality rates was limited; the increase at age 65+ years is consistent with increases in incidence rates reported from cancer registries. Using multiple causes of death vs. only the underlying cause results in substantially higher MDS-related death rates, shows the impact of changes in the classification of myeloid neoplasms and emphasizes the importance of reducing cardiovascular disease mortality in MDS patients.     

The histone LSD1 demethylase in stemness and cancer transcription programs

DNA and histone chromatin modifying enzymes play a crucial role in chromatin remodeling in several biological processes. Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a relevant player in the regulation of a broad spectrum of biological processes including development, cellular differentiation, embryonic pluripotency and cancer. Here, we review recent insights on the role of LSD1 activity in chromatin regulatory complexes, its functional role in the epigenetic changes during embryonic development, in the establishment and maintenance of stemness and during cancer progression.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Patient navigation pathway and barriers to treatment seeking in cancer in India: A qualitative inquiry

Cancer is a leading cause of mortality worldwide. Early diagnosis and treatment of cancer may curb the growing burden of the disease. Understanding cancer patients’ navigation pathways for seeking treatment is important in order to facilitate early diagnosis and treatment. With this background we conducted a hospital-based cross-sectional study comprising 68 randomly selected cancer inpatients in a tertiary cancer specialty hospital in Odisha, India, to explore the treatment-seeking pathways of the cancer patients and the barriers and enablers in seeking treatment. Financial constraint is one of the major reasons for the delay in accessing treatment, even when patients are suspected of or diagnosed with cancer. Low awareness of the presenting signs and symptoms of cancer and limited knowledge of the availability of cancer diagnosis and treatment facilities are major factors contributing to delay. Family and friends’ support is found to be the major enabling factor toward seeking treatment. Generation of awareness of cancer among the general population and primary-care practitioners – including those in alternative systems of medicine – is important. Information on diagnostic and treatment services appears to be a felt need.     

Cancer incidence and mortality in people aged less than 75 years: Changes in Australia over the period 1987–2007

BackgroundAustralia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified.MethodsWe used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age–sex specific rates (average of 1986–1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006–2008). We limited the analyses to people aged less than 75 years.ResultsThere was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (?2259), bowel (?1797), breast (?773) and stomach (?577). Other notable falls were for cancers of the prostate (?295), cervix (?242) and non-Hodgkin lymphoma (?240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (?1705), bladder (?1110) and unknown primary (?904).ConclusionsThe reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.