Tough Opponent Research Articles

Combretastatin A-4 disodium phosphate and low dose gamma irradiation suppress hepatocellular carcinoma by downregulating ROCK1 and VEGF gene expression.

Hepatocellular carcinoma (HCC) is a tough opponent. HCC contributes to 14.8% of all cancer mortality in Egypt. There are many choices for management of HCC; however tumor relapse has been reported in animal and clinical studies. This study was conducted to investigate the impact of low dose γ-irradiation (LDR) and combretastatin A-4 disodium phosphate (CA-4DP) on HCC recurrence. HCC was induced in male Wistar albino rats by oral administration of N-nitrosodiethylamine (NDEA) for 17 weeks. We evaluated the expression of the endothelial cell marker (CD31) by immunostaining. Expression of Rho Associated Coiled-Coil Containing Protein Kinase 1(ROCK1) and Vascular endothelial growth factor (VEGF) expression was assessed by real-time PCR after (6, 24 and 48 h). Our results showed that expression of CD31 and gene expression of ROCK1 and VEGF was significantly repressed at all-time intervals by combination therapy ofLDR and CA-4DP as compared with untreated NDEA/HCC group and NDEA/HCC groups treated with either LDR or CA-4DP alone, (P < 0.05). Our study demonstrated the additive effect of LDR in combination with CA-4DP in suppression of HCC.

Disseminated cancer cells in the peritoneal cavity: what can we do when we detect them?

washes obtained at surgery was recognized. Results of the examination are currently incorporated in the local stage classifi cation as the CY category, in which CY1 stands for positive cytology and classifi es the patient automatically into Stage IV [3]. The prognostic signifi -cance of free cancer cells in the peritoneal washes was also observed among patients who were entered onto the Dutch D1 vs D2 trial [4]. However, this was not suf-fi cient to arouse enough interest to cause Western inves-tigators to consider revising the Tumor Node Metastasis (TNM) classifi cation. One of the reasons may have been that accurate diagnosis of peritoneal washing samples through morphology of the fl oating cells was a formi-dable task. A more quantitative method may have been preferable but was not available at that time.Beginning in the early 1990s, several investigators turned to molecular diagnosis by immunostaining and reverse-transcriptase polymerase chain reaction (RT-PCR) to detect minimal residual disease and occult metastasis in various body components [5]. Of these, an attempt to apply the RT-PCR technique for detection of free cancer cells in the peritoneal cavity was a success [6] — much more so than detection in the bone marrow aspirates and peripheral blood whose association with clinical outcome was inconsistent for gastric cancer [7]. The relevance of detecting carcinoembyonic antigen (CEA) mRNA in the peritoneal washes as a prognostic determinant and predictor of peritoneal carcinomatosis was confi rmed not only through an independent valida-tion study by the same investigators [8] but more soundly among other institutions from numerous countries. The positive predictive value of CEA RT-PCR has not been fl awless [6], however, and the pursuit of an optimal target mRNA is ongoing. Several attempts have been reported using various target mRNAs, among which a combination of markers that are less sensitive but highly specifi c could be the most promising [9]. Ultimately, a good marker or set of markers may in due course be ling studies. Other issues that Cancer recurrence after surgery apparently is due to regrowth of microscopic residual disease that could neither be seen at surgery nor visualized with preopera-tive imaging studies. Gastric cancer is feared for its capacity to metastasize through various metastatic pathways, of which metastasis through the lymphatic pathway is the most frequently observed. However, it is believed in some countries, including Japan, that a certain degree of lymphatic metastasis can be controlled by conducting extended lymphadenectomy. Most sur-geons in Japan have actually seen numerous occasions when gastric cancer with pathologically confi rmed nodal metastasis is cured by D2 dissection alone, and are educated to believe that a failure to perform adequate nodal dissection will result in locoregional recurrence. Postoperative irradiation of the gastric bed would there-fore be a logical solution to augment a suboptimal surgery, of which D0 dissection is a notable example, and was actually found to signifi cantly improve survival of resectable gastric cancer in North America where locoregional recurrence is commonly observed after the curative surgery [1].Peritoneal metastasis, on the other hand, is a tough opponent. This could be a consequence of free cancer cells shed from the serosa of the T3 stage cancer. In addition, cancer cells could also be mechanically scraped off from the stomach or may leak out from the lymphat-ics during surgical manipulation. Peritoneal carcinoma-tosis has been reported to be the most frequent pattern of disease failure after D2 dissection [2], which, as men-tioned above, eradicates the cause for local recurrence. For several decades, Japanese surgeons have been exploring whether detection of free cancer cells in the peritoneal cavity could predict the risk for recurrence and hence lead to any alteration of the treatment strat-egy for that particular patient. Consequently, the rele-vance of a histopathologic examination of the peritoneal

EARLY ROUND UPSETS AND CHAMPIONSHIP BLOWOUTS

I. INTRODUCTION Popular discussions of tournament play often celebrate the success of underdogs in early rounds and decry the prevalence of unexciting finals. Such a pattern might be just a statistical illusion. There are many early round matches, so some upsets are inevitable, and there is only one final, so it is unlikely to be the most exciting match of the tournament. In this article we consider instead whether the pattern might have a real foundation in the strategic allocation of effort by tournament participants. We analyze a two-round tournament in which a favorite and underdog play in each of the two semifinals, and then one player from each match advances to the final. Victory in a match is probabilistic in that the chance of winning is increasing in each player's relative quality and in his relative effort expenditure. (1) Each player has a fixed amount of effort to exert over the two rounds, unused effort is of no value, and the only payoff is from winning the tournament. To maximize the chance of winning, each player must balance out the benefits of expending more effort in the semifinal against the opportunity cost of having less effort available for the final. Favorites and underdogs both have an incentive to conserve resources for the final, but the trade-offs they face are different. A favorite plays a weak opponent in the semifinal, but is likely to face a tough opponent in the final, so it has a strong incentive to hold back. Conversely, an underdog already plays a tough opponent in the semifinal, so it has less incentive to conserve effort for the final. (2) Because of these different incentives, we find that in any symmetric Nash equilibrium underdogs exert more effort than favorites do in the semifinal. The extra effort does not fully compensate for lower ability, and underdogs are still likely to lose, but the chance of an upset rises. In the final round each player expends all its remaining resources, so differences in abilities are no longer compressed by strategic considerations. Instead, an underdog who makes it to the final has fewer resources left to spend than the favorite, so differences in abilities are amplified and the chance of a blowout by the favorite rises. If a favorite loses to an underdog in the early rounds it is often accused of looking past the underdog to its next match. Even if a player's strategy is optimal ex ante, it might turn out to be unsuccessful ex post, so such criticism is often unfair. Our results imply that it is rational for the favorite to hold back on resources in the semifinal even if it correctly anticipates that in equilibrium the underdog will be playing harder. Sometimes the strategy will backfire, but on average the favorite benefits from being in a better position for the final. These results are derived using a standard contest model in which each player's probability of victory in a match is a strictly increasing function of his ability and effort. (3) Such models were first developed to analyze rent-seeking (Tullock 1967, 1980), and similar models appear in a wide variety of areas including patent races (Loury 1979), election campaigns (Snyder 1989), compensation schemes (Nalebuff and Stiglitz 1983), career ladders (Lazear and Rosen 1981), lobbying (Baye et al. 1993), and sports contests (Szymanski 2003). (4) More specifically, we model the contest as a sequential elimination ladder tournament in which players first compete in separate groups and the winners then compete against each other (Rosen 1986). Our result that underdogs do indeed try harder than favorites in the semifinals contrasts with that of Rosen (1986, P. 707-8). Because the favorite has a better chance of victory in the final, Rosen finds that winning a semifinal match is more valuable to the favorite, so the favorite tries harder than the underdog. We reach the opposite conclusion because we assume that there is a fixed supply of effort to be used across rounds and unused effort in the tournament has no value. …

The CP Molecule Labyrinth: A Paradigm of How Endeavors in Total Synthesis Lead to Discoveries and Inventions in Organic Synthesis

AbstractFor Abstract see ChemInform Abstract in Full Text.

The CP molecule labyrinth: a paradigm of how endeavors in total synthesis lead to discoveries and inventions in organic synthesis.

Imagine an artist carving a sculpture from a marble slab and finding gold nuggets in the process. This thought is not a far-fetched description of the work of a synthetic chemist pursuing the total synthesis of a natural product. At the end of the day, he or she will be judged by the artistry of the final work and the weight of the gold discovered in the process. However, as colorful as this description of total synthesis may be, it does not entirely capture the essence of the endeavor, for there is much more to be told, especially with regard to the contrast of frustrating failures and exhilarating moments of discovery. To fully appreciate the often Herculean nature of the task and the rewards that accompany it, one must sense the details of the enterprise behind the scenes. A more vivid description of total synthesis as a struggle against a tough opponent is perhaps appropriate to dramatize these elements of the experience. In this article we describe one such endeavor of total synthesis which, in addition to reaching the target molecule, resulted in a wealth of new synthetic strategies and technologies for chemical synthesis. The total synthesis of the CP molecules is compared to Theseus' most celebrated athlos (Greek for exploit, accomplishment): the conquest of the dreaded Minotaur, which he accomplished through brilliance, skill, and bravery having traversed the famous labyrinth with the help of Ariadne. This story from Greek mythology comes alive in modern synthetic expeditions toward natural products as exemplified by the total synthesis of the CP molecules which serve as a paradigm for modern total synthesis endeavors, where the objectives are discovery and invention in the broader sense of organic synthesis.

A Contingency Approach to Understanding Negotiator Behavior as a Function of Worldmindedness and Expected Future Interaction

Abstract A contingency approach was taken to investigate the effects of worldmindedness and expected future interaction on negotiators' behavioral reactions to a tough opponent. Results showed that internationalists (individuals who favor a worldview of the problems of humanity) who expected to have future interactions with a tough opponent were more conciliatory early in negotiations, relative to internationalists not expecting future interactions. Nationalists who expected to have future interactions with a tough opponent were more contentious early in negotiations, relative to nationalists not expecting future interactions. This pattern of results is attributed to the different concerns and cognitive structures of internationalists and nationalists.

Kuga Katsunan (1857-1907)

The purpose of my paper is to introduce Kuga Katsunan's works on local autonomy and notables in modern Japan.(1) Kuga Katsunan is well known as one of the conservative and nationalistic journalists. He made a lot of comments on social, political and economic reform in modern Japan. He also made a big contribution to the heated controversy on what local government should be. He was really a tough opponent to bureaucratism in Meiji era.(2) After Meiji Restoration in 1868, Japanese leaders considered it necessary to establish a Western legal system as well as Western frame of government in order to achieve modernization. It was remarkable that within a few years Westernization became a national goal and was carried out rapidly even with a considerable degree of popular enthusiasm. But resistance on the part of conservative nationalists appeared in the late 19 century. The nationalists insisted that Japan should reconcil traditional elements with Westernization in order to keep national identity. Kuga Katsunan wrote in his newspaper that the form of local government is far less important than the spirit (Japanese tradition and custom) in which it is worked.(3) Until the end of World War II there was a history of lack of autonomy in Japanese communities. As the result of postwar refom, autonomy was given to local administrative units down to the village level. But autonomy still remains weak in Japan. So I believe that Kuga Katsunan's view on local autonomy gives us some suggestions even today.