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Platostoma palustre jelly is a traditional food. It has been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim of this study was want to analyze the components of commercially traditional herbal tea (P. palustre) in Taiwan. The commercial herbal tea (P. palustre) was kindly provided by Yueta Agricultural Biotechnology Inc. The detection methods of the components of commercially traditional herbal tea (P. palustre) were followed the analysis protocols in Taiwan Herbal Pharmacopeia (IV). The levels of chlorogenic acid, rosmarinic acid, caffeic acid, and rutin were detected via using high-performance liquid chromatography / photodiode array detector (HPLC-PDA). The level of astragaloside was detected by using high-performance liquid chromatography / evaporative light scattering detectors (HPLC-ELSD). In this analysis, the levels of chlorogenic acid, astragaloside, and rutin were not detected. The levels of rosmarinic acid and caffeic acid were 46.96 μg/mL and 29.29 μg/mL, respectively. Taken all results together, the components of commercially traditional herbal tea (P. palustre) were detected via HPLC-PDA and HPLC-ELSD. The major components of commercially traditional herbal tea (P. palustre) were rosmarinic acid and caffeic acid. Based on the results of this assay, it is speculated that the herbal tea has the functional properties that are considerable potential for physiological function regulations.

Inflammatory bowel diseases (IBD) are multifactorial chronic intestinal disorders. Currently, mesalamine etc. and therapeutic strategies were suggested for IBD therapy. However, the etiology of IBD remains unclear which is an ongoing challenge and side effects of therapeutic drugs must be also considered. Thus, the aim of this study was to establish an optimal mouse model of IBD for the drug and therapeutic strategy investigations. Herein, 12 mice with 2% dextran sulfate sodium (DSS)-induced colitis (the negative control group) were via oral administration. Twelve mice were administered with drinking water without 2% DSS (the normal control group) via the same method as DSS-induced mice. At the end of the experiment, the body weight (BW), the stool appearance/status, the macroscopic and microscopic colonic injuries, and myeloperoxidase (MPO) activity were monitored, measured, and scored. The results showed that BALB/c mice’ BW decreased on D6-D8 of 2% DSS induction and then BALB/c mice’ BW continuously increased until D13 of the experiment. The stool appearance/status was seen soft stool on D2 of 2% DSS induction. The soft stool was mainly occurred on D2-D6 of 2% DSS induction. In addition, the watery stool was occurred on D4 of 2% DSS induction and was continuous until the end of the experiment (D14). The macroscopic colonic injuries were showed that colon length of the negative group (2% DSS-induced group) was significantly shorter than that of the normal control group (p < 0.001). The colon weight of the negative group was significantly increase than that of the normal control group (p < 0.001). The colon weight / length ratio in the negative group was significantly higher than that of the normal control group (p < 0.001). According to the histopathologic scores (evaluation of the microscopic colonic injuries), the scores of area, ulceration, inflammation, and edema in the colon tissues of the negative group was significantly higher than that of the normal control group (p < 0.001). The total histopathologic scores in the negative group was significantly higher than that of the normal control group (p < 0.001). The myeloperoxidase (MPO) activity in the inflamed colon tissue of the negative group was significantly higher than that of the normal control group (p < 0.001). Taken all results together, a DSS-induced ulcerative disease mouse model was successfully established. We hope that this animal model may be a useful tool for the research of the better therapeutics for IBD.

Allergic rhinitis (AR) was also called hay fever which was a type of nasal inflammation when the immune system overreacts to environmental allergen exposures. AR’s clinical symptoms included a runny or stuffy nose, sneezing, red, itchy, watery eyes, and eye swelling. The fluid in the nasal cavity was usually clear. Patients with AR can affect sleep and work qualities. Seriously, the AR symptoms can also cause asthma, allergic conjunctivitis, or atopic dermatitis. Therefore, it is an important issue to attenuate AR symptoms and research the novel therapeutic drugs for AR patients. The purpose of this study was to introduce an easy-to-establish experimental mouse model of AR. In this study, the male BALB/c mice were divided respectively into as the Group A (n = 12) and the Group B (n = 12). Group A and Group B were designed as the normal control and RA, respectively. BALB/c mice in Group B were sensitized by intraperitoneal injection of ovalbumin (OVA) on day 0, day 4, day 13, and day 20, followed by continuous nasal administration of OVA solution once per day between day 21-43. BALB/c mice in Group A received sensitization of intraperitoneal injection of phosphate-buffered saline (PBS) on day 0, day 4, day 13, and day 20 and continuous nasal administration of PBS instead of OVA once per day between day 21-43. Before and after sensitization, the frequencies of nasal symptoms (sneezing, nasal rubbing) were recorded and counted. Results were showed that sneezing times in Group B were higher than Group A on D29, D30, D36, and D43 of the experiment. The sneezing times in Group A were significant higher on D29 and D30 of the experiment. However, the sneezing times in Group B were significant higher on D29, D30, D36, and D43 of the experiment. The rubbing times in Group B were higher than Group A on D29, D30, D36, and D43 of the experiment. The rubbing times in Group A were significant higher on D30 and D43 of the experiment. However, the rubbing times in Group B were significant higher on D29, D30, D36, and D43 of the experiment. Based on these results, a successful mouse model of AR has been established. We hope that this RA mouse model will provide a tool for the research of the novel AR therapeutic drugs and apply these novel AR therapeutic drugs to attenuate the AR symptoms in AR patients in the future.

Faced with the impact of extreme climate, countries have proposed carbon dioxide emission reductions, hoping to achieve carbon neutrality by 2050, and Taiwan’s industries must also face the transformation of low-carbon green energy. Light-emitting diode (LED) is a cost effective semiconductor device that produces light within a narrow bandwidth of wavelength through electroluminescence. Recently, LED technology has attention to apply in the area of food production, preservation, and safety. At present, some researches have been demonstrated that the antimicrobial LED visible light is less anti-microbial efficacy than ultraviolet (UV) light. However, the antimicrobial LED visible light has been recognized as an alternative technology to UV light since it is an environmentally friendly and safe technology for human and animals. For this reason, LED technology has recently received attention for applying in many test fields as laboratory, pig farms, computer, bio-medical industries etc. In this study, this novel clean and disinfect tool-novel environment-cleaned LED devices were tested in the various fields and obtained the positive results as the application of novel environment-cleaned LED devices on anti-fungal efficacy, and ethylene, PM2.5, and harmful gas degradations in laboratory, anti-bacterial and virus efficacy in laboratory and/or pig farms, anti-microbial notebook panel development, and anti-colorectal cancer in vitro. In the future, we wish this novel environment-cleaned LED devices will friendly used in human and animal environments to decrease the harmful matters in the environments.

Platostoma palustrejelly is a traditional food.Platostoma palustrehas been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim ofin vivostudy was to determine the effects of herbal tea (Platostoma palustre) on blood glucose regulation. The commercial herbal tea (Platostoma palustre) was kindly provided by Yueta Agricultural Biotechnology Inc. Adult male 18 Institute of Cancer Research (ICR) mice [8 weeks old; body weight (BW) between 31-33 g] with specific pathogen-free conditions were used for this study. All ICR mice were divided respectively the normal control group (n = 6), the negative control group (n = 6), and the herbal tea group (n = 6). The ICR mice (the negative control group and the herbal tea group) were intraperitoneally injected with streptozotocin (65 mg/kg BW) and nicotinamide (230 mg/kg BW) for inducing the symptoms of hyperglycemia. In the herbal tea group, the herbal tea (10 mL/kg BW) was administrated to ICR mice by gavage. To monitor the blood glucose levels in ICR mice, blood was obtained from the tail of ICR mice, and blood glucose levels were determined using the external glucometer. Blood glucose measurements were conducted once in ICR mice before the experiment and were detected once per month after the experiment. Additionally, the change of ICR mice’ BW, the blood glucose of ICR mice, and the observation of ICR mice’ behavior were monitored and detected during the experiment. The results of this experiment showed · Weight change: the weight gain of the negative control group and the herbal tea group were significantly lower than those of the normal control group and there was no significant difference between the negative control group and the herbal tea group. · Fasting blood glucose and postprandial blood glucose: the fasting blood glucose of the negative control group was significantly higher than that of the normal control group, while the herbal tea group had a tendency to lower the fasting blood glucose, but there was no significant difference compared with the negative control group. The postprandial blood glucose level results showed that the negative control group was significantly higher than the normal control group. The postprandial blood glucose level of the herbal tea group was between the normal control group and the negative control group at the 4thweek administration with the herbal tea. At the 8thweek administration with the herbal tea, there was a significant difference compared with the negative control group. · Oral glucose tolerance test (OGTT): 4 to 12 weeks after hyperglycemia was induced, the blood glucose levels of the negative control group at each OGTT test point were significantly higher than those of the normal control group. The blood glucose level at the test point tended to decrease, but there was no significant difference from the negative control group. By calculating the area under the OGTT curve, it was found that the area under the curve of the negative control group was significantly higher than that of the normal control group, while the results of the herbal tea group at the 8thand 12thweeks were significantly lower than those of the negative control group. Taken all results together, the hyperglycemia was successfully induced in the experimental ICR mice. After administrating with the herbal tea, the fasting blood glucose level of the ICR mice tended to improve. In addition, a significant improvement was seen in the results of postprandial blood sugar and oral glucose tolerance test effectiveness. Therefore, based on the results of this experiment, it is speculated that drinking the herbal tea for 3 months has considerable potential for blood glucose regulation, which can be used as the basis for the development of related products of the herbal tea in the future.

Supplementary Materials and Methods from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

Supplementary Figure 1 from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

Supplementary Figure 3 from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

Supplementary Figure 5 from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

Supplementary Figure 4B from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

Supplementary Figure 2 from Activation of DNA Methyltransferase 1 by EBV LMP1 Involves c-Jun NH2-Terminal Kinase Signaling

EBV latent membrane protein 1 (LMP1) activates cellular DNA methyltransferases, resulting in hypermethylation and silencing of E-cadherin. However, the underlying mechanism remains to be elucidated. In this study, we show that LMP1 directly induces the dnmt1 promoter activity through its COOH-terminal activation region-2 YYD domain. Using (i) LMP1 mutants, (ii) dominant negative mutants c-jun NH2-terminal kinase (JNK)-DN, p38-DN, and constitutive active mutant IκB, as well as (iii) dsRNAs targeting c-Jun, JNK, and tumor necrosis factor receptor–associated death domain protein, and (iv) signal transduction inhibitors, we show that LMP1-mediated DNA methyltransferase-1 (DNMT1) activation involves JNK but not nuclear factor κB and p38/mitogen-activated protein kinase signaling. In addition, LMP1 is unable to activate dnmt1-P1 promoter with activator protein-1 (AP-1) site mutation. Chromatin immunoprecipitation assay results also confirm that LMP1 activates P1 promoter via the JNK-AP-1 pathway. Furthermore, chromatin immunoprecipitation assay data in LMP1-inducible cells disclose that LMP1 induces formation of a transcriptional repression complex, composed of DNMT1 and histone deacetylase, which locates on E-cadherin gene promoter. Treatment with JNK inhibitor, SP600125, prevents the formation of this repression complex. Statistical analyses of the immunohistochemical staining of 32 nasopharyngeal carcinoma (NPC) biopsies show LMP1 expression (18 of 32, 56.25%), DNMT1 expression (31 of 32, 97%), and phospho-c-Jun (27 of 32, 84.38%), suggesting that overexpression of these proteins is observed in NPC tumor. Overall, these results support a mechanistic link between JNK-AP-1 signaling and DNA methylation induced by the EBV oncogene product LMP1. (Cancer Res 2006; 66(24): 11668-76)

Sunlight contains ultraviolet (UV) light that causes sunburn and makes the skin age faster, leading to more wrinkles as older. The UV light can come from the natural and artificial sources. Moreover, UV light has shorter wavelengths than the visible light. Therefore, people’ eyes can’t see UV, but people’ skin can feel it. In this study, the in vivo skin health test efficacy modules have been established via the detection of skin’s moisture retention (%), skin’s cytokine expression levels, enzymatic expressions in the skin, the expression levels of hyaluronic acid (HA), collagen type I, melanin, and malondialdehyde (MDA) in the skin, and the experimental mice’ skin thickness and lesions via histo-pathologic examination. According to the results, the clinical behavior observation indexes of Institute of Cancer Research (ICR) mice in each group were normal during the experiments. Moreover, all ICR mice were survival until the end of the experiments. The moisture retention (%) of skin in ICR mice in UVB group was significant decrease after D1, D3, and D5 of UVB irradiation compared to the normal control group. Based on the IL-1β, IL-6 and TNF-α analysis expressions, both IL-1β and IL-6 expressions in UVB group were significantly increase than the control group, while there was no significant difference in the TNF-α expression between the groups. ICR mice’ skin enzymatic expressions in each group presented that catalase (CAT) expression and superoxide dismutase (SOD) activity in UVB group were significantly lower than the control group. The MDA expression in UVB group were significantly higher than the control group. The HA and collagen type I expressions in UVB group were significantly lower than the control group. However, the melanin expressions in UVB group and the control groups were not significantly different. The matrix metalloproteinase 2 (MMP-2) expressions in UVB group was significantly higher than the control group. The skin epidermal thickness in UVB group was significantly thicker than the control group. The dermal thickness in two groups was not significantly different. The number of sunburn cells in the derma in UVB group was significantly increase than the control group. The solar elastosis in the derma in two groups was not significantly different. Based on the above results, we have successfully established in vivo skin health test efficacy modules to evaluate the status of skin health. We hope the modules should be provide for the research and development (R&D) of the effective treatment included drugs and therapeutic strategies.

Many studies have been verified that human retina contains a large amount of carotenoids such as lutein and zeaxanthin, especially the concentrations of lutein and zeaxanthin in the retina and macula are 1,000 times higher than other tissues in human. Therefore, lutein and zeaxanthin play an important role in the health of human vision. The research and development (R&D) of agricultural functional materials or products for eye protection is urgently needed. In this experiment, except for the normal control group, the other groups were irradiated with light-emitting diode (LED) light at the range of 600-1,000 lux for 12 hours / day for 6 weeks. All BALB/c mice were fed with the normal composition for 6 weeks during the experiment. BALB/c mice in the negative control group and three sweet potato leaf ethanolic extracts (SPLEE) groups were fed SPLEE [0.31, 0.62, and 1.23 mg/kg body weight (BW), respectively] for 6 weeks by gavage during the experiment. During the experiment, the eye status of BALB/c mice in each group were observed every week. At the end of the experiment, the BALB/c mice were sacrificed and their eyes in each group were collected for hematoxylin & eosin (H&E) staining, immunohistochemical (IHC) staining, free radical detection, and the detection of cytokine gene expressions (IL-6; interleukin-6 and TNF-α; tumor necrosis factor-α) and caspase-3 gene expression. Based on the results of this experiment, no obvious lesions by ophthalmoscopy were observed in the eyes of BALB/c mice in three SPLEE groups. H&E and IHC staining results showed that the consumption of high dose (1.23 mg/kg BW) of SPLEE significantly improved retinal outer nuclear layer (ONL) thickness, which was compared to the negative control group. Other evaluation indicators included retinal out segments-inner segments (OS/IS) thickness, glial fibrillary acidic protein (GFAP) staining, and middle-wavelength opsin (M-opsin) staining, showed no significant difference among three SPLEE groups and the negative control group. The free radical detection results showed that no statistical difference between all groups (p > 0.05), however, the trend showed that the free radicals in the high and middle doses (1.23 and 0.62 mg/kg BW) of SPLEE groups were lower than those in the negative control group and the low dose (0.31 mg/kg BW) of SPLEE group. The results of IL-6 and TNF-α gene expression showed that the normal control group and three SPLEE groups were significantly lower than the negative control group (p < 0.05), while the gene expression of caspase-3 was not significantly differences between all groups (p > 0.05). Taken these results together, the high dose SPLEE (1.23 mg/kg BW) has the better potential for improving the retinal ONL thickness and anti-inflammatory effects under LED irradiation.

Over-nutrition rather than under-nutrition is an important public health challenge in some developed countries. However, the under-nutrition is a major problem according to the global perspective. Therefore, the research and development (R&D) of agricultural functional materials or products for the prevention of fat accumulation is urgently needed. In this experiment, Sprague Dawley (SD) rats in the normal control group were fed with the normal composition for 8 weeks during the experiment. SD rats in the negative control group and three sweet potato fermented products (SPFP) groups were fed a high fat diet for 8 weeks during the experiment. According to the experimental design, three doses SPFP [250, 500, and 1,000 mg/kg body weight (BW)] will be administered after 4 weeks of feeding the high fat diet. During the experiment, BW of the SD rats was recorded every week and blood, liver, and body fat were collected for analysis of body fat rate, blood lipid content, blood glucose content, liver lipid content, and liver and renal functions. Based on the results, the consumption of SPFP does not affect liver and kidney functions, indicating that SPFP is a safe and edible agricultural material. BW change of the normal control group was significantly lower than that of the negative control group and three SPFP groups (p < 0.05). In addition, there was no significant difference in the BW change rate among the groups eat the high fat feed (p > 0.05), but the trend of BW change rate in the low and middle doses of SPFP groups was lower than that in the other high fat feed groups. The food utilization rate of the high fat diet group was significantly higher than that of the normal diet group (p < 0.05). The body fat rate of the normal control group was significantly lower than that of the high fat feed groups (p < 0.05). There was no significant difference between the high fat feed groups (p > 0.05). However, the trend showed that the body fat rate of the low and middle doses of SPFP groups were lower than that of the negative control group and the high dose of SPFP group. In addition, the results of other measurement indicators such as blood lipid content, blood glucose content, and liver lipid content did not show any negative effects of SPFP. Based on the above results, although SPFP on the prevention of body fat accumulation was not significantly exhibited, however, the trend shows that the low and middle doses of SPFP can decrease body fat production. Taken these results together, SPFP may has the potential for the prevention of fat accumulation.

Platostoma palustrejelly is a traditional food.Platostoma palustrehas been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim of this study was to determine the effects of ethanolic extracts and commercial herbal tea ofPlatostoma palustrein inhibiting colorectal cancer cell viability. The ethanolic extracts ofPlatostoma palustreby using 90% ethanol for extraction. In this study, 2-fold serial dilution of 100 mg/mLPlatostoma palustreextracts were applied. On other hand, the same dilution fold was also performed for 100% commercial herbal tea withPlatostoma palustre. Additionally, CT-26 and HT-29 colorectal cancer cell lines were also used in this study. After co-culturing for 24 hours, the cell viability of CT-26 and HT-29 colorectal cancer cell lines were performed by using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. According to these data, the 1.56-100 mg/mLPlatostoma palustreextracts possessed the significant inhibition effects of CT-26 colorectal cancer cell viability. The 3.13-100% commercial herbal tea withPlatostoma palustrepossessed the significant inhibition effects of CT-26 colorectal cancer cell viability. The 6.25-100 mg/mLPlatostoma palustreextracts possessed the significant inhibition effects of HT-29 colorectal cancer cell viability. The 25-100% commercial herbal tea withPlatostoma palustrepossessed the significant inhibition effects of HT-29 colorectal cancer cell viability. However, the 0.39-3.13 mg/mLPlatostoma palustreextracts possessed the significant promoting effects of HT-29 colorectal cancer cell viability. The 0.39-12.5% commercial herbal tea withPlatostoma palustrealso possessed the significant promoting effects of HT-29 colorectal cancer cell viability. Comparison of CT-26 and HT-29 cell lines was on the cell viability afterPlatostoma palustreethanolic extracts and commercial herbal tea treatments, CT-26 cell line was better sensitive than HT-29 cell line on the inhibition of cell viability after treatment ofPlatostoma palustreethanolic extracts and the commercial herbal tea. Taken these results together,Platostoma palustreethanolic extracts and commercial herbal tea may have a potential for inhibiting the growth of colorectal cancer cells.

Eukaryotic cells can store and converse excess lipid to the cytosolic lipid droplets. Adipogenesis of preadipocytes has been often used to study the molecular basis and the effect of obesity drugs on fat cell conversion. Many methods were developed for the detection of the cytosolic lipid droplets as Nile red, BODIPY 493/503 (4, 4-difluoro-1, 3, 5, 7, 8-pentamethyl-4-bora-3a, 4adiaza-s-indacene), BODIPY 665/676, 1,6-diphenylhexatriene (DPH), DAPI, Hoechst, Sudan III, and Oil-red O. The differences in the spectral properties of these lipophilic dyes and their advantages of each are discussed. In this study, an in vitro flow cytometric detection method was established for the detection of lipid-accumulated cells. Commonly, the longer the period of adipogenic induction, the greater the quantity of lipid in fat cell can accumulate. Thus, to determine whether increasing the fat stored within a cell would result in the greater granularity. 3T3-L1 cells in culture were hormonally induced for adipogenesis. Then, these cells were dissociated and analyzed in a flow cytometer at 0, 5, and 10 days post-induction. After adipogenic induction, the cells had become increasingly heterogeneous in their cellular granularity. The cells containing greater granular structure were markedly increased, and this increase in granularity positively correlated with the time of the post-adipogenic induction. On the other analysis, the 0 and 10 days post adipogenic induction of 3T3-L1 cells were gated for 4 regions. The R1 region contains cells with a level of granularity similar to that seen in the control cells (non-adipogenic induction), whereas R2 to R4 regions contain cells with increasing granularity. According to all data, we have successfully established an in vitro flow cytometric detection method for the detection of lipid-accumulated cells. We wish this method will be applied on the research of obesity drugs and the design of therapeutic strategies for obesity in the future.

Platostoma palustre (Pp) jelly is a traditional food. Pp has been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim of this study was to evaluate the ethanolic extracts of Pp’ genotoxicity. The ethanolic extracts of Pp by using 40% ethanol for extraction. Evaluation of genotoxicity of ethanolic extracts of Pp by micronucleus assay was performed in vivo. During the in vivo genotoxicity-evaluated experiment, the experimental animal’s clinical behavior, body weight (BW), food consumption, and the percentage of RET/RBCs (reticulocytes/red blood cells) and MN-RET/RETs (micronucleated reticulocytes/reticulocytes) after the treatments of Pp ethanolic extracts were evaluated. Both sexes Institute of Cancer Research (ICR) mice were given three daily treatments by intraperitoneal injection of 2 mg/kg of mitomycin C (genotoxicity induction) or by oral route of 200 μL of PBS (normal control group). Until 48 h after the last treatment, K2-EDTA-anticoagulated peripheral blood specimens were collected. These blood samples were processed for the microscopy-based analysis using Giemsa stain and the percentage of reticulocytes and micronucleated reticulocytes was determined. The results were shown that the experimental animal’s clinical behaviors were normal in all groups. The BW and food consumption were no significant difference between all groups. RET/RBCs (‰) in male or female ICR mice in the negative control group, the normal control group, the high dose of Pp ethanolic extract group, the middle dose of Pp ethanolic extract group, and the low dose of Pp ethanolic extract group were respectively 7.8 ± 0.8 / 8.6 ± 0.8, 23.2 ± 1.5 / 22.1 ± 1.3, 22.8 ± 1.6 / 22.1 ± 1.7, 23.2 ± 1.5 / 22.6 ± 1.0 and 22.2 ± 1.9 / 23.9 ± 1.9; MN-RET/RETs (‰) in male or female ICR mice in the negative control group, the normal control group, the high dose of Pp ethanolic extract group, the middle dose of Pp ethanolic extract group, and the low dose of Pp ethanolic extract group were 2.0 ± 0.0 / 2.0 ± 0.0, 43.2 ± 10.6 / 39.6 ± 10.9, 1.8 ± 0.4 / 1.6 ± 0.5, 1.6 ± 0.5 / 1.4 ± 0.5, and 1.8 ± 0.4 / 1.6 ± 0.5, respectively. Both RET/RBCs (‰) and MN-RET/RETs (‰) in male or female ICR mice in the negative control group were significantly difference than the other groups (p < 0.001). Taken all results together, Pp ethanolic extracts were without genotoxicity. Therefore, Pp ethanolic extracts were safety.

Background Single incision laparoscopic colectomy (SILC) and single incision robotic colectomy (SIRC) are both advanced minimally invasive operative techniques. However, studies comparing these two surgical methods have not been published. The purpose of this study is to compare and evaluate the short-term outcomes of SIRC with those of SILC. Methods A total of 21 consecutive patients underwent SIRC and 136 consecutive patients underwent SILC in separate institutes between January 2013 and December 2019. We used retrospective cohort matching to analyze these patients. Results Prior to matching, patients who underwent SIRC had a lower percentage of American Society of Anesthesiologists (ASA) grades III–IV (5% vs. 19%, P = 0.11) compared with patients who underwent SILC. The SIRC group revealed a higher proportion of sigmoid colon lesions and anterior resections than the SILC group (61% vs. 45%, P = 0.16). After 1:4 cohort matching, 21 patients were enrolled in the SIRC group and 84 patients were enrolled in the SILC group. No statistically significant difference in terms of operative time (SIRC: 185 ± 46 min, SILC: 208 ± 53 min; P = 0.51), estimated blood loss (SIRC: 12 ± 22 ml, SILC: 85 ± 234 ml; P = 0.12), and complications (SIRC: 4.7%, SIRC: 7.1%; P = 0.31) was observed between these groups. Length of postoperative hospital stay (SIRC: 8.3 ± 1.7 days, SILC: 9.3 ± 6.5; P = 0.10) and number of harvested lymph nodes (SIRC: 21.3 ± 10.3, SILC: 21.3 ± 9.5; P = 0.77) were also similar between the two groups. In subgroup analysis, numbers of harvested lymph node is less in SIRC than SILC (SIRC: 18.1 ± 4.7 vs. SILC: 18.9 ± 8.1, P = 0.04) in anterior resection. Conclusion SIRC and SILC are safe and feasible procedures with similar surgical and pathological outcomes for right- and left-side colectomy.

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA PIK3CA N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the PIK3CA N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant PIK3CA N345K might be associated with everolimus sensitivity.

The effectiveness of transversus abdominis plane block (TAP) on pain management after laparoscopic colorectal surgery (CRS) remains unclear since the only relevant meta-analysis on this topic did not separate laparoscopic CRS from open CRS. The aim of the study was to compare the analgesic efficacy and safety of TAP with non-TAP in patients undergoing laparoscopic CRS.Four databases were searched for randomized controlled trials (RCTs) on this topic using relevant keywords. Two authors independently completed evidence selection, data extraction, and critical appraisal. Available data were pooled in the random-effects model, and point estimates with 95% confidence interval (CI) were reported for postoperative pain at rest and on coughing, opioid consumption, length of hospital stay, and adverse events.A total of 14 RCTs (n = 1216) contributed to the present synthesis. Pooled result showed that patients in the TAP group had lower pain at rest than those in the non-TAP group at postoperative 2-h (mean difference [MD] = -1.42; P 0.05), 4-h (MD = -0.97; P 0.05), 12-h (MD = -0.75; P 0.05), and 24-h (MD = -0.61; P 0.05). Patients in the TAP group also had lower postoperative pain on coughing than those in the non-TAP group on the first day (MD = -1.02; P 0.05). Moreover, TAP had lesser postoperative opioid consumption than non-TAP (standardized mean difference, -0.26; P 0.05; I-square = 20%), and there were non-significant differences in hospital stay and adverse event between the two groups.Intraoperative TAP is a safe and feasible pain management for laparoscopic CRS, particularly it is recommended when patient-controlled analgesia is not delivered. Therefore, laparoscopic TAP block might be a favorable administered strategy.

Background: Prostate Cancer (PCa) is the second most common male cancer worldwide and the most common cancer in males over 65 years old. PCa is the sixth most common cancer in Taiwan, and its incidence rate has increased gradually over the past 30 years. PAPR inhibitors are the only type of targeted drug approved by the FDA to treat advanced castration-resistant prostate cancer (CRPC) that has grown after the hormone therapy drugs. This study aimed to characterize the genomic profile of Taiwanese PCa and explore whether there are potential treatment guidances derived. Methods: Formalin-fixed paraffin-embedded (FFPE) tumor tissues from 99 patients diagnosed with PCa and collected at Chi-Mei Medical Center (CMMC) were subject to next-generation sequencing using ACTOnco® CGP panel that cover coding regions of 440 cancer-related genes. Genomic alterations (GAs) and signatures, including single nucleotide variations (SNVs), short insertions and deletions (InDels), copy-number variations (CNVs), fusion genes, tumor mutations burden (TMB), and microsatellite instability (MSI) status were retrieved. The gene mutation prevalence was compared with the Western population using the TCGA prostate cancer dataset. Results: A total of 1558 variants was identified, including 215 SNVs, 22 InDels, 1178 CN gain and 135 homozygous deletions. Similar to the Western population, the most frequently mutated genes were SPOP (21.2%), KMT2C (10.1%), MUC16 (8.1%), TP53 (6.1%), ARID2 (5.1%), IDH1 (5.1%), PTGS2 (5.1%). Further analysis showed that 12 patients harbored deleterious/likely deleterious mutations in genes implicated in homologous recombination (HRR) DNA repair pathway, including three BRCA2, two CDK12, BRAD1 and ARID1A, respectively, and one ATR, ATM and PALB2, respectively. All BRCA2 mutations were predicted to be germline origin and only one-third of 12 HRR mutants had a biallelic gene loss. Median TMB calculated from NGS data is 0.6 muts/Mb (range 0 to 4.5) and all samples are microsatellite-stable (MSS). Therapeutically actionable gene and pathway analysis revealed that up to 24.2% of patients harbored at least one aberration against FDA-approved targeted drugs, such as MET copy number (CN) gain (11.1%), mTOR pathway aberration (6.1%), HRR gene biallelic loss (4%), BRAF activating mutation (4%), IDH1 activating mutations (4%), EGFR CN gain (3.0%), FGFR1 CN gain (2.0%), MET fusion (1.0%) and BRAF fusion (1%). Conclusion: This CGP study unraveled the genomic profile of Taiwanese prostate cancers, and the results showed that GAs identified could serve as a potential biomarker to guide personalized, targeted therapies in one-fourth of patients. Citation Format: Kien Thiam Tan, Chia-Ling Wu, Yen-Jung Lu, Ka-Po Tse, Chien-Feng L Li. Characterization of the genomic landscape and actionable mutations in Taiwanese prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5103.

Background Genetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients. Methods We sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets. Results Postulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target. Conclusions Genetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.

Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in both immunocompetent and immunocompromised patients. CMV is a ubiquitous Herpesviridae virus with a wide spectrum of pathologies in humans. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome, whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised. The clinical manifestations of CMV colitis or proctitis are demarcated by bloody diarrhea, ulcerations, ulcero-infiltrative changes, and pseudomembranous formation on colonoscopy. Gastrointestinal CMV infections complicated with deep rectal ulcer and fistula formation are rare in patients with systemic lupus erythematosus. Ganciclovir is also the gold standard therapy for CMV colitis or proctitis.

Purpose To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. Methods and materials A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U test were used to make nonparametric comparisons. Results Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. Conclusion TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.

Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up. Via pathway-driven massive parallel genomic sequencing, a germline mutation at FANCA D1359Y was identified. We identified several recurrent mutations in DNA methylation (TET1, V873I), the β-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) by comparing the genetic events between benign and malignant gastric polyps. Furthermore, we revealed gastric polyposis susceptible genes and genetic events promoting malignant transformation using pathway-driven targeted gene sequencing.

Background Patient-derived xenograft (PDX) tumor model has become a new approach in identifying druggable tumor mutations, screening and evaluating personalized cancer drugs based on the mutated targets. Methods We established five nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome sequencing (WES) and genomic mutation analyses were performed to search for genetic alterations for new drug targets. Potential drugs were applied in two NPC PDX mice model to assess their anti-cancer activities. RNA sequencing and transcriptomic analysis were performed in one NPC PDX mice to correlate with the efficacy of the anti-cancer drugs. Results A relative high incident rate of copy number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in > 90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients’ plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with liver metastatic was treated with Palbociclib, had stable disease response and a drop in Epstein Barr virus (EBV) EBV titer. Conclusions Our integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC.

Background and Objectives: To evaluate the predictive factor for and patterns of distant metastasis in patients with rectal adenocarcinoma receiving total mesorectal excision (TME). Methods: We enrolled 217 consecutive patients who had histologically confirmed rectal adenocarcinoma and underwent surgery at Taipei Medical University- Wanfang Hospital between January 2000 and December 2014. TME was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. We performed univariate and multivariate Cox regression analyses of the distant metastasis rate in all patients to evaluate predictive factors. Overall survival (OS) rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: A multivariate Cox regression analysis of the distant metastasis rate in patients with rectal adenocarcinoma identified tumor locations and American Joint Committee on Cancer (AJCC) stages as prognostic risk factors. The adjusted hazard ratios (aHRs) of distant metastasis for the upper-third, middle-third, and AJCC stage I-II cancers were 0.08 (95% CI, 0.01-0.69; p = 0.021), 0.41 (95% CI, 0.15-0.99; p = 0.047), and 0.20 (95% CI, 0.10-0.66; p = 0.008), respectively. The 5-year lung metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 0%, 3.37%, and 13.33%, respectively (log-rank, p = 0.001), and the 5-year liver metastasis rates among patients with upper-, middle-, and lower-third rectal cancers were 2.12%, 9.10%, and 11.76%, respectively (log-rank, p = 0.096). The 5-year OS rates also differed with different rectal adenocarcinoma locations. The 5-year OS rates for upper, middle, and lower rectal cancers were 96%, 86%, and 64%, respectively (log-rank, p < 0.001). Conclusion: A poor OS rate and high lung or liver metastasis rate were observed in distal rectal adenocarcinoma. Longer intensive surveillance of the chest, abdomen, and pelvis after TME in distal rectal adenocarcinoma could be necessary.

Accompanying with the rapidly increasing scarcity of the Earth's limited resources, the recycling-based society is an imperative objective of sustainable development and is also the future worldwide trend. Forestry waste can be regarded as important environmental resources. The potential applications of forestry waste resources in green energy included the biomass-derived fuel, bio-ethanol, and bio-diesel. Forest waste is the by-product of the wood utilization industry in Taiwan. In this study, the forest waste derived fuels were prepared with the waste cooking oil. The combustion behaviors of the forest waste derived fuels were also investigated. The characteristics of the derived fuel made from forest waste with 20% waste cooking oil showed that the ash content is less than 10% and its calorific value reached 5,000 kcal/kg. The results show that the fuel prepared in this work from the forest waste mixed with waste cooking oil is suitable for use as an alternative fuel and also reduces the global greenhouse gas emissions.

Background and Objectives: To investigate critical prognostic factors for local recurrence in patients with rectal adenocarcinoma. Methods: We enrolled 221 consecutive patients who had histologically confirmed adenocarcinoma of the rectum and underwent surgery in our hospital between January 2000 and December 2014. Total mesorectal excision was performed in all patients undergoing a sphincter-sparing procedure or abdominal perineal resection of rectal cancer. To evaluate prognostic factors for local recurrence, we performed univariate and multivariate Cox regression analyses of the local recurrence rate in all patients. Overall survival rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test. Results: After the inclusion of only model variables of local recurrence with the highest or lowest univariate risk, a tumor size of

TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.

// Hung-Chih Hsu 1, 2 , Tan Kien Thiam 3 , Yen-Jung Lu 3 , Chien Yuh Yeh 2, 4 , Wen-Sy Tsai 2, 4 , Jeng Fu You 2, 4 , Hsin Yuan Hung 2, 4 , Chi-Neu Tsai 5 , An Hsu 3 , Hua-Chien Chen 3 , Shu-Jen Chen 3 , Tsai-Sheng Yang 1, 2 1 Division of Hematology-Oncology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan 2 College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan 3 ACT Genomics, Neihu Dist., Taipei 114, Taiwan 4 Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333, Taiwan 5 Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan Correspondence to: Shu-Jen Chen, e-mail: sjchen@actgenomics.com Tsai-Sheng Yang, e-mail: a481124@cgmh.org.tw Keywords: BRAF, metastatic colorectal cancer, RAS, mutation, cetuximab resistance Received: July 17, 2015 Accepted: February 18, 2016 Published: March 12, 2016 ABSTRACT Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF , PIK3CA , KRAS (exons 3 and 4), NRAS , PTEN , and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS , NRAS , or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS , and BRAF mutations predict response to cetuximab treatment in mCRC patients.

Background: With more hormonal therapies (HT) based treatment (tx) available, predictive markers that could lead to a selection of the optimal tx is necessary. The predictive role of ctDNA mutations in ER+/HER2- MBC after prior HT is less well characterized in Asian patients (pts). Methods: ER+/HER2- MBC pts starting HT based salvage tx after refractory to at least one-line of HT were eligible. ctDNA was extracted from pre- and post-tx plasma and prepared for next-generation sequencing (NGS) analysis. The targeted NGS mutations included regions of ESR1 ligand-binding domain, PIK3CA mutation hotspots, and TP53 mutation hotspots. 96% of the samples were sequenced at an average depths >10000x using the Ion Torrent platform. Progression-free survival (PFS) was defined from the start of the salvage tx to the date of progression. Results: From 2015/08 to 2019/04, a total of 129 and 70 pts treated with HT based tx had pre- and post-tx ctDNA tested, respectively. The median age is 60 (32-92). 14%, 7%, 55%, and 19% of pts received HT only, HT + CDK4/6 inhibitor, HT + everolimus, and HT + metronomic chemotherapy, respectively. With mutation ctDNA > 0.5% as a threshold for positive calling, 79 (61.2%), 33 (25.6%), and 23 (17.8%) pts have at least one ESR1, PIK3CA, and TP53 mutation, respectively and 48 (37.3%) pts have >1 ESR1 mutation genotypes. When compared to other clinical trial data, Asian ER+ MBC pts had significantly higher ESR1 mutation rate as compared to the Western population (p < 0.001) (Table 1). Detectable PIK3CA and TP53 mutation pre-tx was significantly (median PFS 9.8 vs 4.8 months (mos), p= 0.002) and marginally (median PFS 7.9 vs 5.2 mos, p = 0.08) associated with shorter PFS, respectively; but neither the presence of at least one single or multiple clones of ESR1 mutation(s) was associated with PFS (p = 0.52). Conversely, pts without any detectable ctDNA mutation had marginally better PFS (median 12.0 vs 6.5 mos, p = 0.051). With respect to the impact of each ESR1 mutation genotype, the presence of E380Q is associated with significantly shorter PFS (median PFS 7.9 vs 3.4 mos, p = 0.033) while Y537S, D538G, and Y537C were not. When the threshold for the positive calling of ctDNA was raised to 2.5%, ESR1 Y537S mutation became a significant factor for shorter PFS (median PFS 9.1 vs 4.4 mos, p = 0.041); PIK3CA remained as a significant factor for shorter PFS (median 9.3 vs 4.4 mos, p Conclusion: PIK3CA and ESR1 Y537S and E380Q mutations detected by ctDNA had predictive impact for late-line HT based tx but PIK3CA mutation is a better predictor marker than ESR1 mutation in pts treated with HT + everolimus. Table 1 A comparison of the proportion and distribution of ESR1 mutation genotypes among the Taiwan cohort and other clinical trial studiesStudiesESR1 mutation (%)% of ESR1-positive patients withY537SD538GY537CPALOMA3 (n = 360) Fribbens et al. 201691(25.3)25565SoFEA (n = 161) Fribbens et al. 201663(39.1)25465FERGI (n = 156) Spoerke et al. 201657(37.3)33545Taiwan cohort (n = 129)79(61.2)538153 Citation Format: Tom Wei-Wu Chen, Ming-Shen Dai, Dwang-Ying Chang, Ching-Hung Lin, I-Chun Chen, Ming-Yang Wang, Ling-Yi Huang, An Hsu, De-Wei Zhuo, Kien Thiam Tan, Yen-Jung Lu, Shu-Han Chang, Ann-Lii Cheng, Yen-Shen Lu. PIK3CA and ESR1 mutations detected in circulating tumor DNA (ctDNA) are predictive factors for late-line hormone-based therapies in ER+/HER2- metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-21.

Background: Bevacizumab-based regimens are used as standard treatments for colorectal cancer. Unfortunately, there are no established predictive markers for bevacizumab response. Methods: Tumor samples from 36 metastatic colorectal cancer patients treated with bevacizumab plus chemotherapy were analyzed by next-generation sequencing of all coding exons of more than 400 genes. Single gene and signaling pathway analyses were performed to correlate genomic data with response. Results: Among the genes most frequently mutated in our cohort, only mutations in PTPRT, a phosphatase involved in JAK/STAT signaling, were associated with response status, with deleterious mutations being enriched in non-responders. Pathway analysis revealed that deleterious mutations in genes of the JAK/STAT pathway, namely in PTPRT and the related gene PTPRD, correlated with resistance. Mutations in RTK/PI3K/RAS, Wnt and TGF&beta, pathways did not associate with response. Lack of response was observed in all patients with deleterious mutations or copy number loss of PTPRT/PTPRD (n = 10), compared to only 30.8% (n = 8) of patients without such alterations (relative risk, 3.25, 95% CI, 1.83&ndash, 5.79, p = 0.0003). Similarly, PTPRT/PTPRD deleterious alterations were associated with shorter progression-free survival, an association that was retained in multivariate analysis (HR, 3.33, 95% CI, 1.47&ndash, 7.54, p = 0.0038). Conclusion: Deleterious alterations in PTPRT/PTPRD are potential biomarkers for bevacizumab resistance.

Background and Objectives: To investigate whether multidisciplinary team (MDT) intervention is associated with improved survival for patients with colorectal adenocarcinoma with liver or lung metastasis (CRA-LLM). Methods: We enrolled 161 consecutive patients with histologically confirmed CRA-LLM at Taipei Medical University-Wan Fang Hospital between January 2007 and December 2017. In total, 75 patients with CRA-LLM received MDT intervention, and 86 patients did not receive MDT intervention. To evaluate prognostic factors for overall death, we performed univariate and multivariate Cox regression analyses of the overall death rate in all patients. Overall survival rates were calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were compared using the log-rank test (P < .001). Results: A multivariate Cox regression analysis of the overall death rate in patients with CRA-LLM showed that age ≤ 65 years, systemic chemotherapy, curative-intent treatments, and MDT intervention are strong prognostic factors. The adjusted hazard ratio of death risk for age ≤ 65 years, systemic chemotherapy, curative-intent treatments, and MDT intervention were 0.60 (95% confidence interval [CI], 0.40-0.92; P = .019), 0.19 (95% CI, 0.12-0.32; P = .001), 0.25 (95% CI, 0.13-0.50; P = .001), and 0.40 (95% CI, 0.25-0.65; P = .001), respectively. The 3-year overall survival rates in patients with CRA-LLM receiving MDT intervention and not receiving MDT intervention were 48.75% and 24.21%, respectively. Conclusion: MDT intervention is associated with improved survival for patients with CRA-LLM.

Table S3. The summary of the cancer-related somatic mutations and CCND1 CNV gain and CDKN2A CNV loss of the 5 NPC-PDX tumors. (PDF 314 kb)

Table S7. Immnunohistochemical (IHC) staining of cyclin D1 in 139 NPC tissues from year 2002 to 2016. (PDF 415 kb)

Figure S3. C666.1 cells and PDX-C666.1 xenograft drug screening. Drug sensitivity tests in (A) C666.1 cells and (B-D) PDX-C666.1 xenograft. The changes in PDX-C666.1 (B) tumor volume, (C) tumor weight (g), and (D) mice body weight are indicated. Abbreviation, GSK, GSK126; DEC, decitabine; GEM, gemcitabine; PAL, palbociclib. (E) Flow cytometry analysis of C666.1 cells in the presence of PAL (0, 0.1, 0.5 and 1Â ÎźM). (PDF 485 kb)

Figure S4. Drug screening in PDX-LN (NPC02F12). PDX-LN (A) tumor volume; (B) tumor weight; and (C) mice body weight change in the presence of DMSO (control), DEC (reduced dose) and PAL. (PDF 395 kb)