Drug resistance, a reversible state of cancer cells?

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prezzo Viagra professional (Stem Cells, Dec 2012) Researchers suggest that resistance to drug treatments may be a normal part of a cancer stem cell’s life.

omprare viagra generico 25 mg consegna rapida a Parma One of cancer’s deadliest features is the development of drug resistance. Scientists have known for a long time that all it takes for an untreatable cancer to grow back is time and a small number of cancer cells that can withstand the drug treatment. More specifically, and in keeping with current theories about cancer progression, cancer recurrence could result from a small number of drug-resistant (or CSCs) that can survive a treatment and regrow the tumor. A recent Stem Cells article by Shinta Kobayashi and a team of collaborators from several Japanese pharmaceutical companies led by Tatsumi Yamazaki reports intriguing findings on how colon CSCs become resistant to drugs (1).

http://cinziamazzamakeup.com/?x=dove-comprare-viagra-generico-200-mg To support the cancer stem cell hypothesis, scientists have been trying to discover new CSC-specific markers for different cancers. In the case of colon cancer, a gene named Lgr5 had been a good CSC marker candidate, because it is specifically expressed in healthy colon stem cells and it is thought that CSCs share some features with the healthy stem cells from the corresponding tissue. Therefore, Yamazaki’s team decided to investigate Lgr5 further.

acquistare viagra generico 50 mg a Firenze Firstly, to detect the expression of Lgr5 in tissues, the researchers raised against Lgr5, which were notoriously unavailable until now. With this tool in hand, the researchers observed that cells from colon cancers that express the Lgr5 gene (Lgr5+) could regrow a tumor when injected into mice much more frequently than cells from the same cancer that do not express the gene (Lgr5-). The observation that Lgr5- cells could form tumors at all may have seemed to undermine the usefulness of Lgr5 as a good CSC marker. But this story was about to get much more interesting.

enter When the authors established Lgr5+ cell lines from cancer samples, they sought to determine if these cells could develop drug-resistance. By exposing Lgr5+ cells in culture to a drug called irinotecan, about half of the cells stopped dividing but survived the treatment. Most notably, these drug resistant cells had lost expression of Lgr5, even though they maintained expression of other known colon CSC markers. Contrarily, when the researchers removed irinotecan from the culture media and re-plated the Lgr5- survivors, the cells recovered Lgr5 expression, proliferative capacity and tumorigenic potential in mice.

follow site Kobayashi and colleagues could also see this drug-induced interconversion of CSCs in vivo; when Lgr5+ cells were injected into mice treated with irinotecan, there was no tumor growth and the cells quickly lost Lgr5 expression. Stopping the irinotecan treatment, however, allowed the cells to recover Lgr5 expression and form tumors indistinguishable from those obtained with Lgr5+ cells that were never exposed to the drug.

http://cinziamazzamakeup.com/?x=acquistare-viagra-generico-a-Verona Previous studies had already shown that healthy colons have a pool of slowly Lgr5- stem cells that can replace faster cycling Lgr5+ stem cells that were lost from the intestinal . Using their antibody on cancer samples, Yamazaki’s team observed both Lgr5+ and Lgr5- stem cells that appeared to be randomly scattered throughout , raising the interesting possibility that drug-sensitive and resistant cells coexist prior to the use of chemotherapy.

source What’s next? One of the most pressing needs may be to find out if Lgr5 expression is simply a surrogate marker for a given CSC regulatory state (drug-sensitive vs. -resistant), or part of the cellular mechanism related to drug resistance. In another intriguing finding, the researchers report that if primary cultures from the cancer samples were denied attachment to a substrate and grown as , only a few of the cells expressed Lgr5 and could initiate tumor growth; but if the cells were grown as on a solid surface, virtually all of them expressed Lgr5 and showed a much greater tumorigenic capacity in mice.

enter site One thing is for sure: Yamazaki’s research team is anything but short of options.

georgia accutane side effects (1) Kobayashi S et al. LGR5-Positive Colon Cancer Stem Cells Interconvert with Drug-Resistant LGR5-Negative cells and are Capable of Tumor Reconstitution. Stem Cells, 2012 Dec;30(12):2631-44. doi: 10.1002/stem.1257.


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When stem cells divide, they give rise to a daughter that becomes any of a number of specialized cell types and another that is identical to its mother (a process known as ‘self-renewal’ of the stem cell). It’s a way that organs have to replenish damaged cells while maintaining a pool of stem cells for future use. Though this is a hotly debated idea, some scientists think that the same happens in cancers: many cells in a cancer do not divide, but cancers grow unrelentessly nonetheless. That is, they argue, because a small number of cancer stem cells keep producing new cancer cells while self renewing, which ensures future waves of tumorous growth.
Antibodies are proteins made by cells of the immune system that recognize and bind foreign proteins found on invading pathogens. In the body, antibodies aid in mounting an immune attack against these foreign invaders. But in the lab, researchers use antibodies to detect proteins of interest. Monoclonal antibodies are all identical to each other because they are produced by a group of identical cells (or clones) derived from one original immune cell (hence the mono-clonal name). By contrast, “poly-clonal” antibodies are a mixture of different antibody proteins produced by the descendants of several non-identical immune cells. Because all antibodies can occasionally recognize and bind additional targets, the more antibody types in a mix, the higher the chance of what scientists call cross-reactivity. Therefore, and given their higher target specificity, researchers tend to prefer ‘monoclonals’ in the lab.
Researchers frequently talk about ‘in vitro’ and ‘in vivo’. in vitro is latin for ‘in glass’, and it’s a historical remnant from the time when researchers did their experiments in glass vials, tubes and culture plates. By contrast, in vivo refers to experiments done with live animals or plants. And what about experiments with cells in culture? Some scientists will refer to them as in vivo, taking into account the bewildering complexity within cells, whereas others can’t overlook the fact that cultured cells are not a living organism and refer to them as in vitro.

As of late, we should add in silico to the list, in reference to biological simulations within computers.

Often, scientists will refer to dividing cells as ‘cycling’ (ie. slowly cycling cells are cells that divide slowly). ‘Cycling’ is short for cells completing their cell cycle (everything that happens from the moment a cell is born until it divides again).
An epithelium is a sheet of cells tightly bound to each other that lines the outer or inner surface of an organ (or a whole organism, in the case of the skin). Thus, the intestinal epithelium is the sheet of cells lining the inside wall of a gut. Epithelia (pl. for epithelium) can be made of one or many layers of tightly packed cells which, in most cases, are of diverse types and fulfill diverse functions. Intestinal epithelia, for instance, are formed by cells that absorb nutrients, cells that produce digestive enzymes and cells that use hormones to inform the rest of the digestive system (and the body) of what is being digested.
Within cancers, some cells differentiate forming structures that somewhat resemble anatomical features of the corresponding organ under normal conditions. In colon cancers, for instance, some cells will attempt to form colonic crypts. In the context of a cancer, these ill-formed structures appear as short hollow ducts within the cancerous mass.
Cells in culture are normally plated on rigid surfaces that allow them to attach and spread. But researchers can pretreat their culture plates and flasks in ways that prevent such cell attachment. In these cases, some floating cells will start agglomerating and form balls of cells that scientists call spheroids.
When researchers plate epithelial cells in culture, they tend to form the type of epithelium from which they were derived. For instance, intestinal epithelial cells will form a single layer of cells, known as a monolayer.

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