![]() ![]() Since MCF-7 cells are representative of cancer cells that do not readily undergo apoptosis, consideration of senescence pathways may play a role in targeting stem cells from such tumors.Īnalysis of double strand break repair in MCF-7 monolayer and mammosphere populations. ![]() No significant difference was seen in the rates of double-strand break repair (DSBR) between the two cell types, but DSBR in mammospheres appears to by-pass the need for H2AX phosphorylation.Įnhanced survival of MCF-7 tumor-initiating cells in response to ionizing radiation is primarily dependent on an inherent down-regulation of the senescence pathway. Our data demonstrate that in comparison to the bulk population of MCF-7 cells (predominantly CD24+/CD44+), the MCF-7 mammosphere cells benefit from a multifaceted approach to cellular protection relative to that seen in monolayer cells, including a reduced level of reactive oxygen species, a more active DNA single-strand break repair (SSBR) pathway, possibly due to a higher level of expression of the key SSBR protein, human AP endonuclease 1 (Ape1), and a significantly reduced propensity to undergo senescence as a result of increased telomerase activity and a low level of p21 protein expression. Expression of key DNA repair and cell cycle regulatory proteins was detected and quantified by western blot analysis. We employed the telomeric repeat amplification protocol to quantify telomerase activity. Apoptosis was quantified by flow-cytometric analysis of annexin V-binding and senescence was analyzed on the basis of cellular beta-galactosidase activity. The latter was also examined by phosphorylation of histone H2AX and formation of 53BP1 and Rad51 foci. Single and double-strand break repair was measured by single-cell gel electrophoresis. To test this hypothesis, we isolated CD24-/low/CD44+ tumor-initiating cells (as mammospheres) from MCF-7 breast cancer cells grown in adherent monolayer culture, and carried out a comprehensive comparison of cell death and DNA damage response pathways prior to and after exposure to ionizing radiation in mammospheres and monolayer MCF-7 cells. The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins, as well as a reduced propensity to undergo apoptosis or senescence. ![]() The Police Benevolent Association said it has, "serious concerns about the message these types of policies send to both police officers and criminals," adding it will, "look forward to discussing these issues with District Attorney Bragg.A subpopulation of cancer cells, tumor-initiating cells, is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy. The Legal Aid Society said in a statement it, "welcomes this memo as a substantive first step to reform an office that long resorted to making excessive bail requests and overcharging our clients," adding, "Meaningful reform demands that these newly announced policies become standard operating procedure officewide, and we urge judges to not stand in the way of these long overdue and necessary reforms." These policies mark a major shift for an office that's earned a reputation for being more heavy handed in its approach to criminal justice. We can have the justice we deserve with the public safety we need," Adams said. "We want everyone to get in the room and operate off of the same playbook. I have not looked over and analyzed exactly what he is calling for," Adams said.īut on the campaign trail, Adams advocated for more services, and also higher bail and incarceration for offenders.Īdams said he hopes to convene a meeting with lawmakers, district attorneys, and law enforcement. What does Mayor Eric Adams think of the new policies? But there are some people out there who are committing violent felonies," City Council member Joe Borelli told CBS2's Dick Brennan. There is nothing wrong with saying you want to exercise stronger discretion in who we sent to prison. "There's nothing wrong with saying you want to decrease the amount of people in our prisons. The new guidelines are framed by principals, including investing more in programs to keep offenders out of jail, reducing the pre-trail jail population, limiting the number of youth tried as adults, and providing more programs to those returning home after incarceration.Ĭritics fear the effects on the people who live or work in Manhattan. ![]() "I had a shootout on my block a month ago. "Obviously, there is going to be a government response, but for fare evasion it's not going to be incarceration, not in Manhattan," Bragg said. The DA said the changes will allow attorneys more time to prosecute violent offenses. ![]()
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