Do neuroendocrine cells in human prostate cancer express androgen receptor?

The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy.     

Do neuroendocrine cells come up large in small cell lung cancer?

Comment on: Park K, et al. Cell Cycle 2011; 10:2140-50.     

Fuel for cancer cells?

Comment on: Whitaker-Menezes D, et al. Cell Cycle 2011; 10:1772-83.     

Stem cells for lung cancer?

Stem cells are believed to be crucial players in tumor development. There is much interest in identifying those compartments that harbor stem cells involved in lung cancer, given the high incidence and recurrence rate of this disease. In this issue of Cell, Kim and colleagues describe a niche in the bronchioalveolar duct junction of adult mouse lung that harbors stem cells from which adenocarcinomas are likely to arise. They enriched, propagated, and differentiated these stem cells in vitro and found that they were activated by the oncogenic protein K-ras. This study provides exciting insights into how the stem cell compartment operates during both normal lung-tissue homeostasis and the development of lung cancer. The new work offers perspectives on possible therapeutic interventions to combat lung cancer.     

Do glial cells control pain?

Management of chronic pain is a real challenge, and current treatments that focus on blocking neurotransmission in the pain pathway have resulted in limited success. Activation of glial cells has been widely implicated in neuroinflammation in the CNS, leading to neurodegeneration in conditions such as Alzheimer's disease and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-a and interleukin-1b not only cause neurodegeneration in these disease conditions, but also cause abnormal pain by acting on spinal cord dorsal horn neurons in injury conditions. Pain can also be potentiated by growth factors such as brain-derived growth factor and basic fibroblast growth factor, which are produced by glia to protect neurons. Thus, glial cells can powerfully control pain when they are activated to produce various pain mediators. We review accumulating evidence that supports an important role for microglial cells in the spinal cord for pain control under injury conditions (e.g. nerve injury). We also discuss possible signaling mechanisms, in particular mitogen-activated protein kinase pathways that are crucial for glial-mediated control of pain.Investigating signaling mechanisms in microglia might lead to more effective management of devastating chronic pain.     

Are cancer cells really softer than normal cells?

Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression.     

Do mycoplasmas cause human cancer?

A linkage between mycoplasmas and malignancy was mainly proposed in the 1960s when human-associated mycoplasmas were becoming of interest given the novel characterization of the human respiratory pathogen Mycoplasma pneumoniae. Associations with leukemia and other malignancies, however, were largely ascribed to tissue-culture contamination, which is now recognized as a significant potential problem in molecular biology circles. A few epidemiological studies, however, continue to raise concern over such a linkage. As well, in vitro data have demonstrated the potential for some mycoplasmas to induce karyotypic changes and malignant transformation during chronic tissue-culture infestation. As cellular and molecular mechanisms for such transformation become studied, a resurgence of interest in this area is inevitable. A role for mycoplasmas in malignancy of any sort is conjectural, but there remains a need to continue with focussed epidemiological and laboratory investigations.     

How do tumor stem cells actively escape from host immunosurveillance?

Tumor stem cells (TSCs) are considered as the "seeds" in tumor development, metastasis and recurrence. Despite the various immunosurveillance mechanisms in the host, TSCs may possess the phenotypic and functional properties to evade host immunosurveillance and immune-mediated rejection in immunologically intact individuals. The mechanisms of TSC recognition and their consequent destruction are actively disturbed by various processes, including altered immunogenicity of TSCs, production of TSC-derived regulatory molecules, and interaction of TSCs with tumor-infiltrating immune cells. In addition to these TSC-mediated mechanisms, the diverse mesenchymal cells and cytokines in the tumor microenvironment are contribute to TSC immune escape. Recent mechanistic studies provide a more comprehensive understanding of TSCs in the biology, prevention, and therapy of solid tumors. This review will focus on the latest findings for mechanisms underlying TSCs' escape from the attack of immune system.     

Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?

Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and pro-inflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosis and malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments.     

Do NK cells regulate human autoimmunity?

Natural killer cells have been shown to regulate autoimmune responses under experimental conditions in animals. However, a similar role for human NK cells has not been investigated, although NK cells constitute a significant fraction of the infiltrating cells in a range of autoimmune diseases. This review investigates the evidence, both theoretical and experimental, for the involvement of these cells in human immunopathology.     

Do cancer cells in human and meristematic cells in plant exhibit similar responses toward plant extracts with cytotoxic activities?

We examined the effect of water extracts of Persea americana fruit, and of the leaves of Tabernamontana divericata, Nerium oleander and Annona cherimolia (positive control) on Vicia faba root cells. We had confirmed in our previously published data the cytotoxicity of these plant extracts on four human cancer cell lines: liver (HepG-2), lung (A549), colon (HT-29) and breast (MCF-7). Vicia faba roots were soaked in plant extracts at dilutions of 100, 1,250, 2,500, 5,000, 10,000, 20,000 ppm for 4 and 24 h. All treatments resulted in a significant reduction in the mitotic index in a dose dependant manner. Root cells treated with T. divericata, N. oleander and A. cherimolia exhibited a decrease in prophase cell percentage, increase in micronuclei and chromosomal abnormalities as concentration increased. The P. americana treatment showed the highest cytotoxic effect on cancer cells, prophase cell percentage increased linearly with the applied concentration and no micronuclei were detected. This study shows that root tip assay of beans can be used in initial screening for new plant extracts to validate their use as candidates for containing active cytotoxic agents against malignant cells. This will greatly help in exploring new plant extracts as drugs for cancer treatment.     

Do estrogens always increase breast cancer risk?

The etiology of breast cancer is closely linked to the female hormone estrogen, with high life-time exposure being suggested to increase breast cancer risk [Nature 303 (1983) 767]. However, there appears to be a disparity between studies attempting to establish an association between high estrogen levels and breast cancer risk. This disparity becomes smaller by taking into consideration a timing factor, and we propose that estrogens can increase, decrease, or have no effect on breast cancer risk, depending on the timing of estrogen exposure. We further propose that the timing of estrogenic exposures may play at least as important a role in affecting breast cancer risk as life-time exposure.     

LOH-proficient embryonic stem cells: a model of cancer progenitor cells?

Cancers are thought to originate in stem cells through the accumulation of multiple mutations. Some of these mutations result in a loss of heterozygosity (LOH). A recent report demonstrates that exposure of mouse embryonic stem cells to nontoxic amounts of mutagens triggers a marked increase in the frequency of LOH. Thus, mutagen induction of LOH in embryonic stem cells suggests a new pathway to account for the multiple homozygous mutations in human tumors. This induction could mimic early mutagenic events that generate cancers in human tissue stem cells.     

Do neural crest cells in the pancreas differentiate into somatostatin-containing cells?

Summary The possibility that the somatostatin cells are derived from the neurectoderm has been questioned in avian embryos. Isotopic and isochronic transplantations of the neural primordium from quail into chick embryos were made at the vagal level (somites 1 to 7). Quail and chick cells can be distinguished by the structure of their nucleus. The somatostatin cells were characterized immunocytochemically. In no case did quail cells showing the immunological reaction originate from the neural crest.     

Will cancer cells be defeated by sodium bicarbonate?

正Chao et al.reported an improved version of the transarterial chemoembolization(TACE)procedure for large hepatocellular carcinoma(HCC),in which 5%sodium bicarbonate was infused into tumors to supplement chemotherapeutic agents.In a small randomized control trial,TACE combined with bicarbonate yielded a 100%objective response rate(ORR),a significant improvement from the 63.6%ORR in the TACE alone group(Chao et al.,2016).This optimized procedure is termed targeting-intratumorallactic-acidosis TACE(TILA-TACE),as the authors expect