Asian Fund Research Articles

Abstract 3465: FANCD2 depletion suppresses tumor growth in esophageal squamous cell carcinoma

Abstract Introduction: Esophageal squamous cell carcinoma (ESCC) has a remarkably high incidence in Northern China. Our next-generation sequencing analysis on familial ESCC samples suggests that members of the Fanconi Anemia (FA) pathway play important roles in ESCC development. Fanconi anemia complementation group D2 (FANCD2) as a key player of FA pathway has multiple cellular functions. It is well-known for its role in DNA damage repair through the FA pathway. Patients with germline FANCD2 mutations are prone to tumor formation. Identifying roles of FANCD2 in ESCC development may enhance our foundation for future development of specific treatment regimens for this deadly disease. Methods and Results: To study the function of FANCD2 in ESCC, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technique to inhibit FANCD2 protein expression by functional knock-out (fKO). As expected, we observed increased DNA damage in FANCD2 fKO cells as shown by Comet assay, consistent with the classic role of FANCD2 in genome integrity. We also observed that the DNA damage by irradiation takes longer to be repaired in FANCD2 fKO cells, indicating that FANCD2 enhances irradiation-induced DNA damage repair but is not necessary. Similarly, cells with FANCD2 fKO are more sensitive to irradiation, as indicated by cell cycle arrest at S/G2 phase. Surprisingly, without inducing any DNA damage, FANCD2 fKO cells also show cell cycle arrest at S/G2 phase. The MTT cell proliferation assay also show that FANCD2 fKO reduces proliferation and colony-forming ability. Consistent with the in vitro data, FANCD2 fKO cells also form smaller tumors in vivo by the nude mouse tumorigenicity assay. Conclusion: These results indicate that FANCD2 plays important roles in ESCC development and suggest a pro-oncogenic feature of wildtype FANCD2 in ESCC. Further investigation is ongoing to examine the functional role and molecular mechanisms of the oncogenic FANCD2, ultimately aiming at improving ESCC disease management. Acknowledgement: We acknowledge the grant support from the Hong Kong Research Grants Council Collaborative Research Fund (C7031.15G) and the Asian Fund for Cancer Research to M.L.L. Citation Format: Chan Lei, Zhuoyou Yu, Lvwen Ning, Mun-Yee Ko, Lidong Wang, Maria Li Lung. FANCD2 depletion suppresses tumor growth in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3465.

Considerations for Asian fund managers under the US New partnership audit regime

PurposeThis paper aims to explain how the Bipartisan Budget Act of 2015, as modified by the Protecting Americans from Tax Hikes Act of 2015, changes the way the US Internal Revenue Service will conduct audits of collective investment vehicles treated as partnerships for US tax purposes.Design/methodology/approachThis study explains the entities covered by the new partnership audit regime, the effective dates of the new regime and steps to be taken by funds covered by the new audit regime.FindingsThe results show that the new regime creates a liability at the partnership level for any unpaid tax, placing the tax burden on current-year partners.Practical implicationsA fund manager should determine whether the new audit regime is applicable to any of the funds he or she is managing and, if so, amend the fund documents to accommodate the new audit rules, providing a mechanism to elect and supervise a partnership representative, a mechanism to allocate the economic burden of the tax to the appropriate partners and a procedure for selecting the method to calculate the amount of the fund’s tax liability attributable to an audit.Originality/valueThis study provides practical guidance from experienced investment, fund and tax lawyers.

Abstract 423: Investigating the germline deleterious rare variants for genetic susceptibility of esophagus squamous cell carcinomas by target sequencing

Abstract Purpose: The genetic basis of esophageal squamous cell carcinoma (ESCC) still remains unclear. Several genome-wide association studies identified some common variants associated with small effects. Here we aimed to identify some rare deleterious variants in cancer predisposition genes, which may contribute to the genetic susceptibility of ESCC with a large effect, using family history-positive (FH+) samples from the Mainland China Henan high-risk region by targeted sequencing. Methods: A two-phase study was conducted, the discovery phase and the validation phase. In the discovery phase, we sequenced the blood DNAs of 214 independent family history ESCC cases and 123 non-ESCC hospital controls by Illumina HiSeq platform using a custom capture kit. The capture kit included more than 1000 genes, which were cancer-related genes, DNA repair genes, and other genes reported in some ESCC functional studies. For each gene, the exonic region plus 3'-UTR, 5'-UTR, upstream and downstream regions were designed for targeted capture with a total capture size of ~11 Mb. The sequencing reads were aligned to the human reference genome (GRCh37/hg19) using burrows-wheeler aligner (bwa). PCR duplication was marked by Picards. Local realignment was performed with genome analysis toolkit (GAKT). Annovar was used to do the annotation. Loss-of-function (LoF) variants, including splicing, stopgain, and frameshift InDel variants in the cases and controls were identified. The damaging effect of the missense variants was predicted by the combination of 4 different bioinformatics tools (CADD score, MutationTaster, SIFT, Polyphen2). We also used the 1000genomes or ExAC dataset as public controls. All the identified LoF variants in BRCA2 were validated by Sanger sequencing. Results: There was a total of 110 LoF genes identified. Pathway enrichment analysis of these genes found that they were enriched in the Fanconi Anemia (FA) pathway after the background correction of all captured genes. BRCA2 is in the FA pathway and was found to have the most LoF variants; this included 6 individuals from the 214 FH+ cases, and only 1 in the control cohort. We did not find many somatic mutations in ESCC tissues in BRCA2. BRCA2 expression was also significantly upregulated in ESCC tumor tissues, as compared to adjacent normal tissues from in-house and 3 other publicly available RNA-seq datasets. The variant spectra of candidate genes were compared with the public controls to filter out some genes. Conclusions: In the discovery study, we identified some LoF variants in BRCA2 and other genes in the FA pathway that may contribute to ESCC genetic susceptibility. Further validation with a larger sample size is now underway. Acknowledgements: This work was supported by the Research Grants Council Collaborative Research Fund grant C7031-15G and the Asian Fund for Cancer Research to MLL. Citation Format: Lvwen Ning, Josephine Mun Yee Ko, Lisa Chan Lei, Li Dong Wang, Maria Li Lung. Investigating the germline deleterious rare variants for genetic susceptibility of esophagus squamous cell carcinomas by target sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 423.

Replica localization in East Asia: the case of the Asian hedge fund industry

ABSTRACTHedge funds exemplify complex finance in the global economy and are appearing in diverse national settings. One question that follows is whether hedge funds in the Asian region have been localized and exhibit significant differences to their US/UK counterparts or whether there is predominantly one global model. The analysis here point to the importance of what is called replica localization, wherein local control has entailed little deviation from the practices of Anglo-American hedge funds. Evidence generated from databases and interviews confirms the largely equivalent structures and strategies found in the new Asian hedge fund sector. The significance is that a small but growing Asian financial space has been carved out that is funded by Asian capital and managed by Asian elites but matches external models. To further delineate globalized finance, comparative research is needed to determine when and why complex finance is either present or absent outside of Anglo-American economies.

Abstract 5234: Rare deleterious germline mutations of candidate genes associated with risk of familial esophageal squamous cell carcinoma (ESCC) by targeted sequencing

Abstract Background and aims: Esophageal cancer (EC) is a deadly disease with poor survival rates of only ∼10%. The EC incidence remains highest in the Shanxi and Henan regions near the Tang Hang Mountain area in Northern China. In endemic esophageal squamous cell carcinoma (ESCC) regions, common familial clustering and historical migration patterns suggest an inherited ESCC genetic susceptibility. We hypothesize that cancer predisposition gene(s) (CPGs) carrying rare deleterious variants play a crucial role in ESCC genetic susceptibility and aim to identify the underlying CPGs of familial ESCC from Henan by applying the targeted sequencing approach. Methods: Our discovery set utilized NGS technology to capture a comprehensive gene panel critical for ESCC by targeted re-sequencing of 1271 selected genes (11 Mb) and sequenced for the germline variants in the blood DNA from 222 familial ESCC individuals and 124 Henan non-cancer controls. Familial ESCC was defined as at least two family members developed ESCC. The custom designed panel contains a cancer panel of 578 gene list (4Mb) and a custom list of 693 (7Mb) ESCC-specific genes derived from various approaches including microarray profiling in FH+ ESCC primary tissues, homozygosity-by-descent (HBD), SNP array-based analysis by both GWAS and candidate gene approaches of our own set of MassArray SNP association data. The data from 346 individuals were processed using the analysis pipeline following the GATK guideline. Briefly, raw fastq reads were mapped using the Burrows-Wheeler Aligner (BWA). PCR duplicates are marked using Picard. The raw variants are called by GATK HaplotypeCaller using a joint genotyping of all samples. Results: Preliminary data analysis for the 346 samples resulted in the final call set comprised of 52328 rare variants. There are 26486 rare variants present in the 222 FH+ ESCC cases, but absent in the 124 controls. The average sequencing coverage was 88X. Principal component analysis (PCA) and multidimensional scaling (MDS) indicated a homogenous population structure between the case and the control populations. Targeted re-sequencing results of the 1271 selected genes in 222 familial ESCC individuals identified a recurrent missense variant in AIM1L (Absent in Melanoma 1-like) in 14/222 (6.3%) of FH+ ESCC patients but absence in the 124 non-cancer control. Data obtained by a melting curve-based genotyping platform by LC480 and LightSNiP assay for high throughput validation of this recurrent SNP in larger sample cohort are underway and will be presented. Conclusions: A SNP in AIM1L may be associated with higher risk for ESCC in Henan and validation in larger cohort is required. The data may provide valuable insight for understanding genetic susceptibility to this deadly cancer. Acknowledgements: We acknowledge the Asian Fund for Cancer Research for grant support. Citation Format: Josephine Mun Yee Ko, Lu wen Ni, Sheyne, Sta Ana Choi, Lisa Chan Lei, Li Dong Wang, Maria Li Lung. Rare deleterious germline mutations of candidate genes associated with risk of familial esophageal squamous cell carcinoma (ESCC) by targeted sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5234.

The Empirical Evidence on Government Bond Market Integration in East Asia

I. INTRODUCTIONSince the 1997 Asian financial crisis, bond market development has been the central pillar of financial cooperation in East Asia. Many scholars argue that while individual countries strive to develop the domestic bond markets, it is also necessary to build a regional bond market, where governments, corporates or other institutions can finance themselves through the regional capital pool in a minimum cost (Shimizu, 2007; Rhee, 2003). From the perspective of investors, bond market integration enables them to diversify the country-specific risks through holding a wide range of bonds both inside and outside the country in a very low cost. (Baele et al., 2004). From the perspective of bond issuers, entrepreneurs with little initial capital or facing credit constraint in small economies can turn to broader capital markets, which implies a strong correlation between the bond market integration and economic growth (Levine, 1997). Less dependency on the long- term borrowing from overseas banks offers East Asia the potential to migrate the double mismatch problem and enhances the region's resilience to negative external shocks.To this end, a number of initiatives have been pursued to promote the regional bond market development in East Asia. Asian Bond Markets Initiative (ABMI) in 2003 is the milestone for the regional governments' cooperation to develop the regional bond market. In the following years, ASEAN+3 economies have continued to move forward through upgrading arrangements, harmonizing institutions and regulations within the region to promote the regional bond market integration. For example, Credit Guarantee and Investment Facility (CGIF) was launched, under the framework of ABMI, to facilitate East Asian corporations to issue local currency denominated bonds by providing credit enhancement in 2010.Asian Bond Fund is another major initiative to promote regional bond market development. The Executive Meetings of East Asia and Pacific Central Banks (EMEAP) launched the ABF 1 with a capitalization of USD 1 billion in 2003. However, due to its small size, ABF 1 had little effect on the market for dollar-denominated government bonds in East Asia. Later, ABF 2, introduced in 2004 with a capital of USD 2 billion, was implemented to purchase local currency bonds from Asian countries. One of their aims is to increase the demand for the regional bonds by investing in a large pool of US dollar denominated government bonds issued by local governments or organizations in eight EMEAP economies, namely, China, Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore and Thailand.Furthermore, because the bond markets in East Asian economies are relatively independent due to different regulations and currencies, to build a regional bond market, East Asian countries try to harmonize bond standards and practices at the national levels to encourage more intra-regional issuance and transaction. As a result, ASEAN+3 Bond Market Forum (ABMF) was established under the framework of ABMI to harmonize the market regulations concerning cross-border transactions in September 2010. The ABMF is constituted of two sub-forums. Sub-Forum 1 (SF1) collects and compares bond market regulations in East Asia, in the meanwhile, Sub-Forum 2 (SF2) tries to standardize regional transaction procedures and harmonize market regulations.Despite the numerous benefits bond market integration may bring to East Asia, the potential risks should not be ignored, such as the financial contagion. The financial instability in one country can be transmitted to the neighboring countries quickly. For example, the Asian financial crisis in November 1997 started in Thailand with the collapse of the Thai baht and rapidly swept over Indonesia, Malaysia, Korea and beyond, generating serious impact on the world economy as a whole. Another example is the outbreak of the European debt crisis, which also reveals the potential risks from the financial integration in the Eurozone. …

Trades of dangers: A study of asbestos industry transfer cases in Asia

In a study of asbestos industry transfers in Asia, we examined the transfer of health and safety measures at the time of industry transfer and resulting health outcomes thereafter. Field surveys were conducted in Japan, Germany, Indonesia, and South Korea over a 5 year period beginning in 2007. The surveys involved interviews and field assessments of health and safety conditions. Even when there were transfers of entire engineering plant processes, we observed that the health and safety measures that should have accompanied the transfer, including technical capacities of risk assessment and management, regulatory protection, and cultural practices, were not actually transferred. According to work environment assessment records, there were differences in airborne asbestos levels of approximately 5-6 fibers/cc between the exporting and importing sides of the transfer. This amounted to a 10 years of time delay in comparable health and safety conditions. These differences resulted in repeated adverse health consequences at each factory operation site. Dangerous transfers of asbestos industry technology have occurred repeatedly over the years with the result that Asia has become the largest consumer of asbestos in the world. No effective internationally accepted safety measures have been introduced in the region. The study results support the need for both improved public awareness and international cooperation, such as sharing of substitute material technologies by the exporting countries, and provide the rationale for the creation of an Asian fund for asbestos victims.

Five outstanding young Chinese scholars received the Third Scholar Award from the Asian Fund for Cancer Research (AFCR) and the US Chinese Anti-Cancer Association (USCACA)

Chinese researchers and physicians are being increasingly recognized for making significant contributions that advance biomedical research, including cancer research, in both China and the world. To facilitate and strengthen collaborations among cancer researchers and physicians in the United States and China, the US Chinese Anti-Cancer Association (USCACA) and the US National Foundation for Cancer Research (USNFCR) have established the Scholar Excellence Award for the USNFCR-USCACA Scholar Exchange and Fellowship Program in Basic, Translational, and Clinical Studies. Since 2010, 5 young Chinese researchers and physicians have received the Scholar Excellence Award for their outstanding achievements in cancer research performed while in the United States, as well as their continuous contributions to eradicate cancer after their return to China. This year, the USCACA joined the Asian Fund for Cancer Research, Ltd. (AFCR) in selecting 5 promising individuals for their excellence in basic or clinical cancer research. Here, we are proud to introduce the 5 winners of the 2012 AFCR-USCACA Scholar Excellence Award: Dr. Xiuli Bi at the College of Life Science, Liaoning University, Shenyang; Dr. Binghui Li in the Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin; Dr. Lina Zhang in the Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin; Dr. Yi Zhang in the Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu; Dr. Yuhua Zhao in the Department of Biochemistry and Molecular Biology, Sichuan University, Chengdu, Sichuan. We have invited these awardees to contribute a short essay that summarizes their achievements in cancer research. As illustrated in their essays, these outstanding young scholars have received excellent training under their US mentors. They have not only made impressive discoveries in the mechanisms underlying the causes or progression of human cancers but also discovered new approaches for improving treatment for cancer patients. Our ultimate goal is to expedite novel cancer drug development by stimulating the translation of lab discoveries into novel cancer treatments, fostering collaborations in clinical cancer drug development, and sharing expert knowledge and medical practices between China and the United States.

The Fund Management Industry in Hong Kong and Asia-Pacific

Hong Kong has the largest number of fund managers, one of the largest fund management industries in Asia-Pacific, and the largest exchange-traded funds (ETFs) market by trading value in East Asia. Nevertheless this sector in common with some others examined in this study, reveals the huge impact the Chinese mainland has had on Hong Kong in terms of activity created and concurrently a relatively modest development of its international position. Some of the main themes to be developed in what follows turn on the following summary observations:Unlike the two other major regions of the world economy, there is no cooperation infrastructure nor even comparable statistics for the fund management industry in Asia-Pacific. Unlike the United States and Europe that have a national or regional industry association to advocate regulation and policy recommendations to the industry, there is no such kind of regional cooperation in Asia. In turn, is a dire lack of comparable statistics in this area across economies in the region not only impedes research but more importantly hinders the development of initiatives, strategies and policies for the region.Internationalism and diversifications. Hong Kong’s and Singapore’s industry survey reports show that the combined fund management industry is larger in Hong Kong, but (as of 2008) it appears to be more internationalized and diversified in Singapore. However, things have gradually changed. Since 2009 large banks and fund houses have started to expand their teams in Hong Kong and/or relocate senior executives to the city. While this relative but notable reconfiguration in the last year or two appears to result from the impact of the China factor, given the sector’s relative preference for greater concentration of expertise the result is also an improved the level of regional importance and internationalism for the Hong Kong fund management industry.The China factor. The enormous and underdeveloped Chinese market is without doubt one of the biggest opportunities for the Hong Kong fund management industry. China’s capital market is still subject to exchange and capital controls and its fund management industry is short of seasoned fund managers. Hong Kong, an open economy with good financial infrastructure and many experienced fund managers, is in pole position to capture the opportunity to service the Chinese market, particularly its new middle-class and expanding wealthy population. Further, it will be beneficial for Hong Kong to deepen its private investors market. In addition to be the gateway for Chinese funds to invest abroad, Hong Kong should also be the gateway for foreign companies that are interested in the Chinese market. An onshore fund management industry. Following the global financial crisis, there is greater appetite in the region and globally for the use of onshore regulated vehicles, which provide greater investor protection and ability to assess and manage risk. In this connection recent changes in European Union directives on investment funds may have a big impact on the Asian fund management industry, which relies heavily on the European market; indeed the offer of funds originating and sold in Asia but registered and marketed from Europe has expanded notably in the recent past. These developments, alongside the concurrent strengthening of Hong Kong’s fund management industry in the same period noted above, strongly suggest a good opportunity for Hong Kong to develop an onshore fund management industry and to seek to become the centre of Asia domiciled funds. However, there is limited information how local authorities want to pursue these goals.