This paper was presented at the conference "Financial services at the crossroads: capital regulation in the twenty-first century" as part of session 2, "Credit risk modeling." The conference, held at ...the Federal Reserve Bank of New York on February 26-27, 1998, was designed to encourage a consensus between the public and private sectors on an agenda for capital regulation in the new century.
After the passage of the Financial Institutions Reform, Recovery and Enforcement Act of 1989, there was an explosion of bank acquisitions of savings and loan associations. From August 1989 through ...June 1990, banks acquired 174 thrifts. Of that number, 121 thrifts were acquired in Resolution Trust Corp. transactions. During the same time period, there were 37 ordinary acquisitions of sound stock thrifts by commercial banks and 16 nontraditional transactions involving bank acquirors of thrifts. A thrift acquisition may be attractive to a bank for either strategic or price reasons. Strategic reasons include the lack of availability of commercial bank targets in a market the commercial bank buyer wants to enter. Also, the thrift branches can make attractive vehicles for consolidation within existing markets. Since the October 1987 stock market crash, the median deal price multiples have shown thrifts to be from 15% to 50% cheaper than commercial bank deals.
The acquisition of resistance is a major obstacle to the clinical use of platinum drugs for ovarian cancer treatment. Increase of DNA damage response is one of major mechanisms contributing to ...platinum-resistance. However, how DNA damage response is regulated in platinum-resistant ovarian cancer cells remains unclear. Using quantitative high throughput combinational screen (qHTCS) and RNA-sequencing (RNA-seq), we show that dual oxidase maturation factor 1 (DUOXA1) is overexpressed in platinum-resistant ovarian cancer cells, resulting in over production of reactive oxygen species (ROS). Elevated ROS level sustains the activation of ATR-Chk1 pathway, leading to resistance to cisplatin in ovarian cancer cells. Moreover, using qHTCS we identified two Chk1 inhibitors (PF-477736 and AZD7762) that re-sensitize resistant cells to cisplatin. Blocking this novel pathway by inhibiting ROS, DUOXA1, ATR or Chk1 effectively overcomes cisplatin resistance in vitro and in vivo. Significantly, the clinical studies also confirm the activation of ATR and DOUXA1 in ovarian cancer patients, and elevated DOUXA1 or ATR-Chk1 pathway correlates with poor prognosis. Taken together, our findings not only reveal a novel mechanism regulating cisplatin resistance, but also provide multiple combinational strategies to overcome platinum-resistance in ovarian cancer.
•Providing multiple potential approaches for treatment of platinum resistant ovarian cancer.•Integrating qHTCS, RNA-seq and clinical studies to elucidate cisplatin resistant mechanism.•DUOXA1-mediated activation of ATR-Chk1 regulates cisplatin resistance in ovarian cancer.
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