LONGITUDINAL CLONAL LINEAGE DYNAMICS AND FUNCTIONAL CHARACTERIZATION OF PANCREATIC CANCER CHEMO-RESISTANCE AND METASTASIZATION

In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones to improve clinical outcomes. Clonal replica tumors (CRTs) is an in vivo platform created specifically to enable robust tracing and functional study of clones within a tumor. The establishment of CRTs is built upon our current concept of tumor heterogeneity, intrinsic cancer cell hierarchy and clonal self-renewal properties. The model allows researchers to create large cohorts of tumors in different animals that are identical in their clonal lineage composition (clonal correlation amongst tumors \u3e0.99). CRTs allow simultaneously tracking of tens of thousands of clonal lineages in different animals to provide a high level of resolution and biological reproducibility. CRTs are comprised of barcoded cells that can be identified and quantified. A critical feature is that we have developed a systematic method to isolate and expand essentially any of the clonal lineages present within a CRT in their naïve state; that is, we can characterize each sub-clonal lineage at the molecular and functional levels and correlate these findings with the behavior of the same lineage in vivo and in response to drugs. Here, based on the CRT model and its concept, we studied differential chemo-resistance among clones, where we identified pre-existing upregulation in DNA repair as a mechanism for chemo-resistance. Furthermore, through stringent statistical testing, we demonstrated orthotopic CRTs to be a powerful and robust model to quantitatively track clonal evolution. Specifically, we longitudinally tracked clones in models of pancreatic ductal adenocarcinoma (PDAC) from primary tumor expansion through metastasization, where we captured unexpected clonal dynamics and “alternating clonal dominance” naturally occurring in unperturbed tumors. Moreover, by characterizing pro- and none-metastasizing clones, we were able to identified key clonal intrinsic factors that determined the nature of tumor metastases. Finally, I will discuss distinct clonal evolution patterns that emerged under different environmental pressures, leading to the hypothesis of “tumor clonal fingerprint”, where the characteristic of a tumor could be defined by actively maintained ratio of different tumor lineages, which could provide measurable insights to how we approach treatments

An Economy-wide Analysis of Impacts of WTO Tiered Formula for Tariff Reduction on Taiwan

In this study we use Taiwan as a case study to provide an economy-wide analysis of impacts on Taiwan of WTO tariff reduction schemes with different combinations of thresholds and reduction rates. The model we utilized in this study is Taiwan General Equilibrium Model with a WTO module (TAIGEM-WTO, hereafter) that is a multi-sectoral computable general equilibrium (CGE) model of the Taiwan's economy derived from Australian ORANI model (Dixon, Parmenter, Sutton and Vincent, 1982). Simulation results show that results are more sensitive to the scheme of tariff-reduction (i.e., Category 1, 2, and 3) than the tiered levels (i.e., A, B, C, and D) and as a strategy we should pay more attention to the arguments related to the amounts of tariff-reduction. Moreover, changes in nominal average tariff rates are more sensitive and shocks to the economy are more severe when we change the tariff reduction categories rather than the tiered levels. This conclusion also applies to the tiered reduction case when only sensitive products are considered. Finally, simulations with sector's bound rate calculated using arithmetic means have bigger effects than those using import values as weights. Therefore, sector's bound rate using import values as weights would be preferred.International Relations/Trade,

Does Long-Term Use of Silver Nanoparticles Have Persistent Inhibitory Effect on H. pylori Based on Mongolian Gerbil’s Model?

It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian gerbil's model

Increasing Ceftriaxone Resistance in Salmonellae, Taiwan

In Taiwan, despite a substantial decline of Salmonella enterica serotype Choleraesuis infections, strains resistant to ciprofloxacin and ceftriaxone persist. A self-transferable blaCMY-2-harboring IncI1 plasmid was identified in S. enterica serotypes Choleraesuis, Typhimurium, Agona, and Enteritidis and contributed to the overall increase of ceftriaxone resistance in salmonellae

Coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (HPV 31)

AbstractObjectiveAdenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection.Case reportWe present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up.ConclusionA literature review revealed that this was a rare case of combined ABC–SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion

Gender Difference in the Relationship of Albuminuria and Arterial Stiffness in Chinese Adults - a 6.6-Year Follow-Up Longitudinal Study

Background/Aims: Brachial–ankle pulse wave velocity (baPWV) reflects the stiffness of muscular arteries. Albuminuria is recognized as a marker of vascular dysfunction. We assessed the association between arterial stiffness and albuminuria in a population-based longitudinal study. Methods: 1116 adults aged ≥ 40 years in the Taichung Community Health Study (TCHS) in 2004 attended a follow-up visit in 2011. Albuminuria was defined as an urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Arterial stiffness was defined as BaPWV ≥ 1540 cm/sec in males and BaPWV ≥ 1480 cm/sec in females, respectively. ∆baPWV was calculated as baPWV at follow-up minus baPWV at baseline, while ∆UACR was calculated as UACR at follow-up minus UACR at baseline. Multiple linear and logistic regression analyses were used to explore the relationship between albuminuria and arterial stiffness. Results: Among 652 subjects without arterial stiffness at baseline, 209 (32%) subjects developed incident arterial stiffness after an average of 6.6 years. In male subjects, baseline albuminuria was associated with development of arterial stiffness (odds ratio: 4.47, 95% confidence interval [CI]: 1.04–19.31) and ∆baPWV was modestly positively associated with ∆UACR. Conclusion: Our results indicated that male adults with albuminuria had an increased risk for developing arterial stiffness

Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is composed of cardiovascular risk factors including insulin resistance, obesity, dyslipidemia, and hypertension. Most of the components of MetS have been linked to the development of neoplasm. The purpose of this study was to evaluate the relationship between individual components of MetS and colorectal adenoma.</p> <p>Methods</p> <p>The study subjects were recruited from a pool of 4872 individuals who underwent a health check-up examination during the period January 2006 to May 2008. Each participant fulfilled a structured questionnaire. MetS was defined based on the America Heart Association and National Heart Lung Blood Institute criteria. Subjects with history of colon cancer, colon polyps, colitis, or prior colonic surgery were excluded.</p> <p>Results</p> <p>A total of 4122 subjects were included for final analysis (2367 men and 1755 women; mean age, 49.6 ± 11.7 years). Of them, MetS was diagnosed in 708 men (29.9%) and in 367 women (20.9%). Among the patients with MetS, 34.6% had adenoma, 31.7% had hyperplastic polyps and 23.3% were polyp-free (p < 0.0001, Chi-square test). The adjusted OR for colorectal adenoma was significantly higher in the subjects with MetS (OR, 1.31, CI: 1.09-1.57). A stronger association between MetS and colorectal adenoma was found in men (OR:1.44, CI:1.16-1.80) than in women (OR:1.04, CI:0.74-1.46). The adjusted OR for adenoma increased as the number of MetS components increased (p for trend = 0.0001 ). When the individual components of MetS were analyzed separately, only central obesity (OR:1.36, CI:1.14-1.63), low HDL cholesterol levels (OR:1.30, CI:1.10-1.54) and high triglyceride levels (OR:1.26, CI:1.04-1.53) were independently associated with colorectal adenoma.</p> <p>Conclusions</p> <p>Of the components of MetS analyzed in this study, central obesity and dyslipidemia are independent risk factors for colorectal adenoma. With regard to the prevention of colorectal neoplasm, life-style modification such as weight reduction is worthwhile.</p

Joint relationship between renal function and proteinuria on mortality of patients with type 2 diabetes: The Taichung Diabetes Study

Abstract Background Estimated glomerular filtration rate (eGFR) is a powerful predictor of mortality in diabetic patients with limited proteinuria data. In this study, we tested whether concomitant proteinuria increases the risk of mortality among patients with type 2 diabetes. Methods Participants included 6523 patients > 30 years with type 2 diabetes who were enrolled in a management program of a medical center before 2007. Renal function was assessed by eGFR according to the Modification of Diet in Renal Disease Study equation for Chinese. Proteinuria was assessed by urine dipstick. Results A total of 573 patients (8.8%) died over a median follow-up time of 4.91 years (ranging from 0.01 year to 6.42 years). The adjusted expanded cardiovascular disease (CVD)-related mortality rates among patients with proteinuria were more than three folds higher for those with an eGFR of 60 mL/min/1.73 m2 or less compared with those with an eGFR of 90 mL/min/1.73 m2 or greater [hazard ratio, HR, 3.15 (95% confidence interval, CI, 2.0–5.1)]. The magnitude of adjusted HR was smaller in patients without proteinuria [1.98 (95% CI, 1.1–3.7)]. An eGFR of 60 mL/min/1.73 m2 to 89 mL/min/1.73 m2 significantly affected all-cause mortality and mortality from expanded CVD-related causes only in patients with proteinuria. Similarly, proteinuria affected all outcomes only in patients with an eGFR of <60 mL/min/1.73 m2. Conclusion The risks of all-cause mortality, as well as expanded and non-expanded mortality from CVD-related causes associated with proteinuria or an eGFR of 90 mL/min/1.73 m2 or greater are independently increased. Therefore, the use of proteinuria measurements with eGFR increases the precision of risk stratification for mortality.http://deepblue.lib.umich.edu/bitstream/2027.42/112804/1/12933_2012_Article_558.pd

Wafer-scale growth of large arrays of perovskite microplate crystals for functional electronics and optoelectronics

Methylammonium lead iodide perovskite has attracted intensive interest for its diverse optoelectronic applications. However, most studies to date have been limited to bulk thin films that are difficult to implement for integrated device arrays because of their incompatibility with typical lithography processes. We report the first patterned growth of regular arrays of perovskite microplate crystals for functional electronics and optoelectronics. We show that large arrays of lead iodide microplates can be grown from an aqueous solution through a seeded growth process and can be further intercalated with methylammonium iodide to produce perovskite crystals. Structural and optical characterizations demonstrate that the resulting materials display excellent crystalline quality and optical properties. We further show that perovskite crystals can be selectively grown on prepatterned electrode arrays to create independently addressable photodetector arrays and functional field effect transistors. The ability to grow perovskite microplates and to precisely place them at specific locations offers a new material platform for the fundamental investigation of the electronic and optical properties of perovskite materials and opens a pathway for integrated electronic and optoelectronic systems.Comment: 8 pages, 4 figure