Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Determining the Temperature-Dependent Characteristic Temperature of Beryllium from Electrical Resistance Measurements

We have developed an intermediate-level laboratory experiment to determine the temperature- dependent characteristic temperature of beryllium. The apparatus used to measure the resistance of a beryllium wire sample between liquid nitrogen and room temperatures was simple. The characteristic temperatures obtained from these data using the Block-Grüneisen model are in reasonable agreement with literature values obtained from resistivity and heat capacity experiments. The experiment introduced students to cryogenic and computer data analysis techniques and forced them to extend their knowledge of the theory of electrical resistance and of characteristic temperatures

Determining the temperature‐dependent characteristic temperature of beryllium from electrical resistance measurements

We have developed an intermediate-level laboratory experiment to determine the temperature- dependent characteristic temperature of beryllium. The apparatus used to measure the resistance of a beryllium wire sample between liquid nitrogen and room temperatures was simple. The characteristic temperatures obtained from these data using the Block-Grüneisen model are in reasonable agreement with literature values obtained from resistivity and heat capacity experiments. The experiment introduced students to cryogenic and computer data analysis techniques and forced them to extend their knowledge of the theory of electrical resistance and of characteristic temperatures

Cooling by Immersion in Liquid Nitrogen

When an object is cooled by immersion in a liquid, there is an unexpected increase in the violence of boiling just before the boiling stops. Most people seem fascinated by this phenomenon yet few are acquainted with its explanation in terms of a change in the heat‐transfer mechanism from film boiling to nucleate boiling. We have developed two variations of an intermediate level undergraduate laboratory experiment to measure the heat‐transfer rate after a sample is immersed in liquid nitrogen. The temperature of the sample, as measured by a thermocouple, is recorded as a function of time using either a potentiometer strip‐chart recorder or a digital voltmeter–microcomputer combination. The heat‐transfer rate as a function of sample temperature is computed from these results, and the reason for the effect is clearly seen

A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster

We have identified an intergenic transcriptional activity that is located between the human HOXA1 and HOXA2 genes, shows myeloid-specific expression, and is up-regulated during granulocytic differentiation. The novel gene, termed HOTAIRM1 (HOX antisense intergenic RNA myeloid 1), is transcribed antisense to the HOXA genes and originates from the same CpG island that embeds the start site of HOXA1. The transcript appears to be a noncoding RNA containing no long open-reading frame; sucrose gradient analysis shows no association with polyribosomal fractions. HOTAIRM1 is the most prominent intergenic transcript expressed and up-regulated during induced granulocytic differentiation of NB4 promyelocytic leukemia and normal human hematopoietic cells; its expression is specific to the myeloid lineage. Its induction during retinoic acid (RA)–driven granulocytic differentiation is through RA receptor and may depend on the expression of myeloid cell development factors targeted by RA signaling. Knockdown of HOTAIRM1 quantitatively blunted RA-induced expression of HOXA1 and HOXA4 during the myeloid differentiation of NB4 cells, and selectively attenuated induction of transcripts for the myeloid differentiation genes CD11b and CD18, but did not noticeably impact the more distal HOXA genes. These findings suggest that HOTAIRM1 plays a role in the myelopoiesis through modulation of gene expression in the HOXA cluster