In 2009, Li, who previously had US citizenship after years working in the United States, renounced his US citizenship. He was thought to have taken up Singaporean citizenship, although Singaporean authorities did not initially provide any confirmation of this. On 28 July 2009, the chairman of One Foundation (the charity fund of Li) announced that Li had indeed become a Singaporean citizen. He was said to have chosen Singapore for its education system for his two younger daughters.
In 2009, he launched his own fitness program, Wuji. The program consists of elements of martial arts, yoga and pilates; Adidas launched a special clothing line for it that bears the initials of "JL".
Li discussed his commitment to philanthropy in an interview with the December 2009 issue of Alliance magazine, stating that "grassroots non-government organizations can help the government in its blind spots. Government relief is not always detail-oriented. Grassroots NGOs can't be as big as a government effort, but they need to be flexible and independent."
Onika Tanya Maraj-Petty (née Maraj; born December 8, 1982), known professionally as Nicki Minaj (/mɪˈnɑːʒ/ min-AHZH), is a Trinidadian-born[a] rapper, singer, and songwriter based in the United States. She is known for her musical versatility, animated flow in her rapping, alter egos and accents. Minaj first gained recognition after releasing three mixtapes between 2007 and 2009. Her debut album, Pink Friday (2010), topped the U.S. Billboard 200 chart. Its fifth single, "Super Bass", reached number three on the U.S. Billboard Hot 100 chart and was certified diamond by the RIAA. Minaj's follow-up album, Pink Friday: Roman Reloaded (2012) explored dance-pop. The lead single, "Starships", peaked in the top five worldwide.
Minaj released her first mixtape, Playtime Is Over, on July 5, 2007, and her second, Sucka Free, on April 12, 2008. She released her third mixtape, Beam Me Up Scotty, on April 18, 2009; it received favorable coverage on BET and MTV. At the time, she was managed by Debra Antney. One of its tracks, "I Get Crazy", reached number 20 on the U.S. Billboard Hot Rap Songs chart and number 37 on the Hot R&B/Hip-Hop Songs chart. After Minaj was discovered by fellow rapper Lil Wayne, she signed a recording contract with his Young Money Entertainment. That November, she appeared with Gucci Mane and Trina on the remix of "5 Star Bitch" by Yo Gotti.
In early February 2010, Minaj made her first two appearances on the U.S Billboard Hot 100 chart with her features on "Knockout" and "Up Out My Face" by Lil Wayne and Mariah Carey respectively. Minaj also appeared on "BedRock" and "Roger That" on the compilation album, We Are Young Money (2009). The singles peaked at numbers two and 56, respectively, in the U.S. Their parent album reached number nine on the U.S. Billboard 200, and was certified gold by the Recording Industry Association of America (RIAA). At Jay-Z's suggestion, Robin Thicke featured Minaj on his single "Shakin' It 4 Daddy". Allison Stewart of The Washington Post stated that, during that time, she "became the go-to girl for artists who wanted to add some skank to their tracks without sullying themselves in the process". Minaj became the first female solo artist to have seven singles simultaneously charting in the U.S.
In May 2021, Minaj released a reissue of her mixtape Beam Me Up Scotty (2009), including new songs previously unavailable on streaming services. The reissue debuted at number two on the U.S. Billboard 200, which gave it the highest debut for a female rap mixtape in the U.S. A song from the reissue, titled "Seeing Green" featuring fellow Young Money rappers Drake and Lil Wayne reached number twelve in the U.S. and appeared in the mid-year "Best Hip Hop Songs of 2021 (so far)" critics list by magazine HipHopDX. Minaj's verse on "Fractions" from the reissue appeared on the mid-year "Best Rap Verses of 2021 So Far" critics list from Complex. In July, Minaj collaborated with fellow rapper Bia on the remix of her song Whole Lotta Money. The remix appeared on several "Best Songs of the Year" lists from publications such as Rolling Stone and NPR.
Sony revealed its intention to adapt Shadow of the Colossus into a movie in 2009. At the time, screenwriter Justin Marks (The Jungle Book, Street Fighter: The Legend of Chun-li) was attached to write.
Minaj released her first mixtape, Playtime is Over, on July 5, 2007, and her second, Sucka Free, on April 12, 2008. That year, she was named Female Artist of the Year at the 2008 Underground Music Awards. She released her third mixtape, Beam Me Up Scotty, on April 18, 2009; it received favorable coverage on BET and MTV. One of its tracks, "I Get Crazy", reached number 20 on the U.S. Billboard Hot Rap Songs chart and number 37 on the Hot R&B/Hip-Hop Songs chart.
After Minaj was discovered by fellow rapper Lil Wayne, in August 2009 it was reported that she signed a recording contract with his Young Money Entertainment. That November, she appeared with Gucci Mane and Trina on the remix of "5 Star Bitch" by Yo Gotti. Minaj also appeared on "BedRock" and "Roger That" on the compilation album, We Are Young Money (2009). The singles peaked at numbers two and 56, respectively, on the U.S. Billboard Hot 100; their parent album reached number-nine on the U.S. Billboard 200, and was certified gold by the Recording Industry Association of America (RIAA). At Jay-Z's suggestion, Robin Thicke featured Minaj on his single "Shakin' It 4 Daddy".
On May 14, 2021, Minaj released a reissue of her 2009 mixtape Beam Me Up Scotty. It debuted at number two on the Billboard 200, becoming the highest debut for a female rap mixtape on the chart. A song from the reissue, titled "Seeing Green" featuring fellow rappers Drake and Lil Wayne (associated with Young Money's lineage alongside Minaj) reached number twelve on the Billboard Hot 100 and appeared on the mid-year "Best Hip Hop Songs of 2021 (So Far) critics list by HipHopDX. Minaj's verse on "Fractions" from Beam Me Up Scotty appeared on the mid-year "Best Rap Verses of 2021 So Far" critics list from Complex. On July 9, 2021, Minaj revealed herself as a feature on the remix of Whole Lotta Money with American rapper Bia. The remix appeared on several "best songs of the year" critics lists from publications such as Rolling Stone and NPR.
The Street Fighter II games were followed by several sub-series of Street Fighter games and spinoffs which include Street Fighter Alpha, Street Fighter EX, Street Fighter III, Pocket Fighter, Super Puzzle Fighter II Turbo and Capcom's Vs. series (which combined Capcom's characters with properties from other companies such as Marvel, SNK, and Tatsunoko). Capcom released Street Fighter IV for the arcades in July 2008, followed by the release for the Xbox 360 and PlayStation 3 consoles in February 2009 and for Microsoft Windows in July 2009. Most recently, Street Fighter V was released for the PlayStation 4 and PC in 2016.
Searches, data extraction, and data analyses were conducted by Dr Xuan Xia and Dr Brian H May. The draft manuscript was drafted by Dr Xuan Xia and Dr Brian H May with critical input from all other authors during the revisions the draft manuscripts. Prof. Qingchun Huang, Dist. Prof. Charlie C. Xue, Assoc. Prof. Anthony L Zhang, Prof. Xinfeng Guo and Prof. Chuanjian Lu provided expert contributions to the conception and design of the project, the methodology, and data interpretation.
In relation to fulvestrant, it is clear that AIs are non-superior in terms of efficacy and tolerability. Clinical data suggests that, in some cases, fulvestrant may increase progression-free survival and overall survival when compared to AIs (Robertson et al. 2009, 2012, 2016, Ellis et al. 2015). Despite this, its poor solubility impairs its oral delivery to the patients, meaning that the administration must be performed by intramuscular injection. This drawback limited its clinical use as first-line therapy in the adjuvant setting. Therefore, the development of new orally available SERDs is a growing field that might strengthen the use of this class of drugs, in the future, for the adjuvant setting (Lai et al. 2015, Liu et al. 2016, Zhang et al. 2017). In fact, there are several oral SERDs that are being studied in clinical trials as the phase I/II non-randomised study of GDC-0810 (Nbib1823835), the dose-escalation phase I trials of AZD9496 (Nbib2248090) and of RAD1901 (Nbib2338349) (Vries et al. 2016, Bardia et al. 2017). For these reasons, AIs remain the gold-standard treatment option in postmenopausal ER+ breast cancer therapy due to their improved clinical efficacy and manageable toxicity profile. Moreover, in recent years, AIs have begun to be administered in drug combinations that will be mentioned throughout this review.
Human aromatase belongs to the cytochrome P450 family and is the product of the CYP19A1 gene on chromosome 15. Aromatase is the only known enzyme in vertebrates that, through the aromatization of the A-ring of androgens, catalyses the biosynthesis of estrogens (estradiol and estrone) from the androgenic precursors (testosterone and androstenedione) (Ghosh et al. 2012). Ghosh et al. using X-ray crystallography solved the structure of aromatase and its enzyme-substrate interaction (Ghosh et al. 2009, 2010). The elucidation of the active site of aromatase gave new insights for the design and discovery of novel AIs (Ghosh et al. 2016).
Several studies have shown that tumours retaining ER expression can escape the limitations of estrogen deprivation, by increasing their hypersensitivity to residual levels of estrogens. Curiously, in these cases, high doses of estrogen are known to inhibit cell growth and induce apoptosis of resistant cells (Masamura et al. 1995, Ellis et al. 2009, Zucchini et al. 2015), though, recent studies have suggested that the exact mechanism of ER hypersensitivity may differ according to estrogen levels (Sikora et al. 2012). Santen et al. reported that the ER-mediated transcription of genes is different when the ER is hypersensitive (Santen et al. 2005). The main mechanisms, in this case, are the interactions with the GFR signalling pathways, together with non-genomic actions near or at the cell membrane (Santen et al. 2009). This suggested that interactions with GFR signalling pathways do not simply restore the normal ER function, but by increasing ER phosphorylation, alter and enhance ER-mediated transcription of genes. This theory is supported by the finding that elevated AKT levels can alter the genome-wide binding pattern of ER compared to the one seen in wild-type cells (Bhat-Nakshatri et al. 2008). Thus, these findings indicate that disrupting GFR signalling may be a more realistic approach in preventing ER hypersensitivity than to abrogate estrogen action. GFR signalling blockade in AI-resistant breast cancer is already under investigation and will be discussed later. 2b1af7f3a8