Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selectedKras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) andStreptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

Ginseng has always been the typical export item in Korean history. Until the 18th century, exporting ginseng was wild ginseng from the mountains. Since the 19th century, exporting ginseng became red ginseng, which was red due to steaming and drying process. Red ginseng was produced by Gaesung merchants, so that these merchants were able to gain the control of the output. Gaesung merchants of the 19th century exported red ginseng to China and made huge economic success. However, when the Korean Empire and Japanese colonical government established red ginseng monopoly, it essentially blocked Gaesung traders from manufacturing and exporting any further of its prized commodity. Then, the traders turned to sun-dried white ginseng as a substitute to red ginseng. As a result, white ginseng production dramatically increased after 1914, which in turn made Gaesung merchants newly aware of the commercial value of white ginseng, which was previously ignored. The traders made good use of the traditional medicine herb market, which opened annually, to promote the expansion of white ginseng sales. Moreover, the merchants also adopted modern marketing techniques, as they founded companies to handle solely white ginseng sales, refreshed packaging to raise commodity values, and made an effort in advertising and mail order sales. Due to such endeavors, demand for white ginseng grew exponentially both in domestic and foreign markets, which generated steady growth of white ginseng prices despite the rapid increase of its supply. This phenomenon naturally brought about the rich economic accomplishments of Gaesung merchants. Through the white ginseng sales activities of Gaesung merchants in post-1910s era, two facts can be newly uncovered. First, the mass consumption of white ginseng today in Korean society took a full-scale step after the 1910s. Second, it was a widely-held view that during the Japanese rule, majority of Korean traditional merchants were economically ruined, while a small minority collaborated with the colonical government to obtain economic success. However, Gaesung merchants in 1910s successfully commercialized white ginseng not with the aid of the Japanese but with their own efforts alone. Such fact reveals that there were other types of traditional merchants during the Japanese colonial period who cannot be explained with the common theory.
Commerce/*history ; History, 20th Century ; Panax/*chemistry ; Plants, Medicinal

Since the late 18th century, the Korean traditional medicine trade witnessed a steady growth. There were lots of stores which sold Korean medicinal herbs in Seoul and every major towns had at least one or more stores in Korea, which led to a subsequent growth of people involved in the trade. However, Korean medicine merchants encountered a new environment with the influx of western medicines after the Opening of Ports and the execution of modern medicine policies. Such change of atmosphere led the merchants to seek new breakthroughs. Some of the merchants found the answer in producing and selling patent medicine. The people in the industry had little knowledge of western medicine, so that they had little choice but to combine their experience of Korean medicine with whatever information they had about western counterpart. Such resolution generated a new kind of medicine known as patent medicine. Patent medicine businessmen observed the new medicine policies of the Korean Empire. Some visionary ones even sought to eagerly utilize the trademark system to secure the selling route. The Japanese colonial government strengthened the medicine policies. It revised the legislature and mobilized administrative powers to manage and control the industry. However, such colonial policies in the 1910s implicated certain limits due to its lack of understanding of Korean medicine industry. Also, the colonial government showed poor efforts in introducing modern medicine facilities and systems, so that the ground was set for the patent medicine business to flourish. Patent medicine enjoyed a high turnover. So, the entrepreneurs endeavored to promote the sales in whatever means necessary. The most basic form of advertisement was through the newspaper. Indirect promotion through newspaper articles, issuing medicine flyers, free gift draw, reputation of an influential expert were widely used for its sales. Consequently, patent medicine industry in the 1910s saw a healthy prosperity. One example of such golden days was the case of Hwapyungdangyakbabg(one of the biggest patent medicine companies), which won a third place along with Kyungsungbangjik, which was the top Korean company at that time, in the advertisement design contest hosted by the classified department of Dong-a Daily in 1926. But actually, a few Japanese medicine merchants led the industry. So prosperity of Korean medicine merchant had its limits.
*Plants, Medicinal ; Legislation, Drug/history ; Korea ; Japan ; Humans ; History, 20th Century ; History, 19th Century ; Government Regulation/history ; Drugs, Non-Prescription/*history ; Colonialism/history ; Advertising/history