Artificial Intelligence-Driven Morphology-Based Enrichment of Malignant Cells from Body Fluid.

Cell morphology is a fundamental feature used to evaluate patient specimens in pathologic analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with the high background of nonmalignant cells, restricting the ability of downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multidimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed a higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low levels or undetectable in presort patient samples. Our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multidimensional morphology analysis, and microfluidic sorting.

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT.

AIMS: Grape seed procyanidin extract (GSE), and milk thistle silymarin extract (MTE) contain structurally distinct polyphenols, and each agent has been shown to exert antineoplastic effects against lung cancer. We hypothesize that combinations of GSE and MTE will additively enhance their anticancer effects against lung cancer. MATERIALS AND METHODS: The anti-proliferative effects of GSE, MTE and combinations were evaluated in lung neoplastic cell lines. A dose range finding (DRF) study to determine safety, bioavailability and bioactivity, followed by human lung cancer xenograft efficacy studies were conducted in female nude mice with once daily gavage of leucoselect phytosome (LP), a standardized GSE, and/or siliphos, a standardized MTE. The roles of tumor suppressors miR-663a and its predicted target FHIT in mediating the additive, anti-proliferative effecs of GSE/MTE were also assessed. KEY FINDINGS: GSE with MTE additively inhibited lung preneoplastic and cancer cell proliferations. Mice tolerated all dosing regimens in the DRF study without signs of clinical toxicity nor histologic abnormalities in the lungs, livers and kidneys. Eight weeks of LP and siliphos additively inhibited lung tumor xenograft growth. Plasma GSE/metabolites and MTE/metabolites showed that the combinations did not decrease systemic bioavailabilities of each agent. GSE and MTE additively upregulated miR-663a and FHIT in lung cancer cell lines; transfection of antisense-miR-663a significantly abrogated the anti-proliferative effects of GSE/MTE, upregulation of FHIT mRNA and protein. LP and siliphos also additively increased miR-663a and FHIT protein in lung tumor xenografts. SIGNIFICANCE: Our findings support clinical translations of combinations of GSE and MTE against lung cancer.

Index-based dietary patterns and stomach cancer in a Chinese population.

OBJECTIVES: Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population. METHODS: Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored. RESULTS: Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects. CONCLUSIONS: Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

Single Cell Mechanotype and Associated Molecular Changes in Urothelial Cell Transformation and Progression.

Cancer cell mechanotype changes are newly recognized cancer phenotypic events, whereas metastatic cancer cells show decreased cell stiffness and increased deformability relative to normal cells. To further examine how cell mechanotype changes in early stages of cancer transformation and progression, an in vitro multi-step human urothelial cell carcinogenic model was used to measure cellular Young's modulus, deformability, and transit time using single-cell atomic force microscopy, microfluidic-based deformability cytometry, and quantitative deformability cytometry, respectively. Measurable cell mechanotype changes of stiffness, deformability, and cell transit time occur early in the transformation process. As cells progress from normal, to preinvasive, to invasive cells, Young's modulus of stiffness decreases and deformability increases gradually. These changes were confirmed in three-dimensional cultured microtumor masses and urine exfoliated cells directly from patients. Using gene screening and proteomics approaches, we found that the main molecular pathway implicated in cell mechanotype changes appears to be epithelial to mesenchymal transition.

Rehabilitation Therapy for Vocal Fold Paralysis Caused by Lung Cancer: A Case Report.

OBJECTIVE: Unilateral vocal fold paralysis (UVFP) can be caused by iatrogenic injury or tumor-induced damage to the recurrent laryngeal nerve. Studies of comprehensive rehabilitation therapies for patients suffering from severe UVFP are limited. The purpose of this case report is to describe an improvement in complete aphonia after comprehensive rehabilitation therapies in a patient with severe UVFP due to a lung tumor. METHODS: An 81-year-old woman with a history of bronchial adenoma had complete aphonia due to compression of the left recurrent laryngeal nerve by the tumor. Dynamic fibrolaryngoscope revealed paralysis of the left vocal fold. The patient was treated with interferential current therapy, vocal training, and kinesiology taping. Indicators of voice recovery were scored according to the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap index. RESULTS: After 10 days of comprehensive rehabilitation treatment, the patient recovered from complete aphonia to normal communication. The hoarseness and breathiness of patient were significantly improved. In addition, the grade, roughness, breathiness, asthenia, strain, and the voice handicap index scores changed from severe to mild or absent. CONCLUSION: This case provided a novel comprehensive treatment for a patient with UVFP, which was safe, cost-effective, and easy to implement in clinic.

Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China.

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.

Bioavailability and bioactivity of free ellagic acid compared to pomegranate juice.

Pomegranates are an excellent source of ellagic acid (EA), ellagitannins (ETs), anthocyanins and other phytochemicals. The health benefits of pomegranate (Pom) have been mainly related to its EA and ET content. The objective of the present study was to determine EA bioavailability and bioactivity from different sources such as pure/free or natural form (PomJ). This was a cross-over study with healthy volunteers consuming one dose of EA dietary supplement (500 mg free EA) vs. one serving of PomJ (237 mL, ∼120 mg of EA) in a random order. Our data showed that there was no difference in plasma EA concentration between PomJ and EA intake; however, urinary dimethylellagic acid glucuronide (DMEAG), normalized to creatinine, was significantly higher after the consumption of PomJ compared to EA. Plasma insulin at 1 h increased after PomJ consumption compared to the baseline while decreased after EA consumption compared to the baseline. Plasma glucose decreased below the baseline 2 h after the consumption of PomJ but not EA. Plasma leptin was significantly decreased at 1 and 2 h after PomJ and EA consumption. Plasma MCP1 decreased only after PomJ but not after pure EA consumption. To conclude, one serving of PomJ provided the same level of EA in blood, while the increase in phase II metabolism of EA and an acute suppression of plasma MCP1 were only observed after PomJ consumption, suggesting that other constituents present in PomJ, in addition to EA, are bioactive and likely play a role in regulating EA phase II metabolism.

Dietary Intake of Fatty Acids, Total Cholesterol, and Stomach Cancer in a Chinese Population.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.

Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.

Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.

A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention.

Grape seed procyanidin extract (GSE) had been reported to exert antineoplastic properties in preclinical studies. A modified phase I, open-label, dose-escalation clinical study was conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome (LP), a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Eight subjects ages 46-68 years were enrolled into the study and treated with escalating oral doses of LP for 3 months. Bronchoscopies with bronchoalveolar lavage and bronchial biopsies were performed before and after 3 months of LP treatment. Hematoxylin and eosin stain for histopathology grading and IHC examination for Ki-67 proliferative labeling index (Ki-67 LI) were carried out on serially matched bronchial biopsy samples from each subject to determine responses to treatment. Two subjects were withdrawn due to issues unrelated to the study medication, and a total of 6 subjects completed the full study course. In general, 3 months of LP, reaching the highest dose per study protocol was well tolerated and no dosing adjustment was necessary. Such a treatment regimen significantly decreased bronchial Ki-67 LI by an average of 55% (P = 0.041), with concomitant decreases in serum miR-19a, -19b, and -106b, which were oncomirs previously reported to be downregulated by GSE, including LP, in preclinical studies. In spite of not reaching the original enrollment goal of 20, our findings nonetheless support the continued clinical translation of GSE as an antineoplastic and chemopreventive agent against lung cancer.

Consumption of garlic and its interactions with tobacco smoking and alcohol drinking on esophageal cancer in a Chinese population.

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.

Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity.

MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA and protein (p21) levels. Transfection of miR-106b mimics reversed the up-regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative and anti-invasive properties in lung cancer cells. Oral gavage of leucoselect phytosome (LP), a standardized GSE to athymic nude mice down-regulated MIR106B mRNA and miR-106b expressions, and increased CDKN1A mRNA expression in tumor xenografts, correlating to significant reduction of tumor growth. To assess bioavailability, GSE and metabolites in plasma levels, between 60-90 minutes after gavage of LP were measured by LC/MS at treatment week 4 and 8. A novel bioactivity assay was also developed using lung homogenates from treated mice co-cultured with human lung cancer cells. LP-treated mouse lung homogenates significantly reduced proliferations of various lung cancer cells. Our findings reveal novel antineoplastic mechanisms by GSE, further define the pharmacokinetics and pharmacodynamics of LP, and support the continued investigation of LP against lung cancer.

Metal-organic frameworks with 1,4-di(1H-imidazol-4-yl)benzene and varied carboxylate ligands for selectively sensing Fe(iii) ions and ketone molecules.

Four new metal-organic frameworks (MOFs) [Zn(L)(bpdc)]·1.6H2O (1), [Co(L)(bpdc)]·H2O (2), [Ni3(L)2(bptc)2(H2O)10]·2H2O (3) and [Cd2(L)(Hbptc)2] (4) were achieved by reactions of the corresponding metal salt with mixed organic ligands of 1,4-di(1H-imidazol-4-yl)benzene (L) and 4,4'-benzophenonedicarboxylic acid (H2bpdc) or biphenyl-2,4',5-tricarboxylic acid (H3bptc). They exhibit varied structures: MOFs 1 and 4 are porous three-dimensional (3D) frameworks, while 2 is an infinite one-dimensional (1D) chain and 3 is a two-dimensional (2D) network. Remarkably, 1 and 4 can act as potential fluorescent materials for sensing Fe(iii) ions and different ketone molecules with high selectivity and sensitivity. In addition, MOF 1 shows selective adsorption of CO2 over N2.

Prebiotic Potential and Chemical Composition of Seven Culinary Spice Extracts.

The objective of this study was to investigate prebiotic potential, chemical composition, and antioxidant capacity of spice extracts. Seven culinary spices including black pepper, cayenne pepper, cinnamon, ginger, Mediterranean oregano, rosemary, and turmeric were extracted with boiling water. Major chemical constituents were characterized by RP-HPLC-DAD method and antioxidant capacity was determined by measuring colorimetrically the extent to scavenge ABTS radical cations. Effects of spice extracts on the viability of 88 anaerobic and facultative isolates from intestinal microbiota were determined by using Brucella agar plates containing serial dilutions of extracts. A total of 14 phenolic compounds, a piperine, cinnamic acid, and cinnamaldehyde were identified and quantitated. Spice extracts exhibited high antioxidant capacity that correlated with the total amount of major chemicals. All spice extracts, with the exception of turmeric, enhanced the growth of Bifidobacterium spp. and Lactobacillus spp. All spices exhibited inhibitory activity against selected Ruminococcus species. Cinnamon, oregano, and rosemary were active against selected Fusobacterium strains and cinnamon, rosemary, and turmeric were active against selected Clostridium spp. Some spices displayed prebiotic-like activity by promoting the growth of beneficial bacteria and suppressing the growth of pathogenic bacteria, suggesting their potential role in the regulation of intestinal microbiota and the enhancement of gastrointestinal health. The identification and quantification of spice-specific phytochemicals provided insight into the potential influence of these chemicals on the gut microbial communities and activities. Future research on the connections between spice-induced changes in gut microbiota and host metabolism and disease preventive effect in animal models and humans is needed.

Fluorescent sensing and selective adsorption properties of metal-organic frameworks with mixed tricarboxylate and 1H-imidazol-4-yl-containing ligands.

Herein, two metal-organic frameworks (MOFs), [Co4(µ3-OH)2(L)(BTB)2(H2O)3]·5.6H2O (1) and [Cd3(L)2(BTB)2(µ2-H2O)]·7.4H2O (2), based on 1,3-di(1H-imidazol-4-yl)benzene (L) and 1,3,5-tri(4-carboxyphenyl)benzene (H3BTB), respectively, have been achieved. Compound 1 is a porous three-dimensional (3D) framework with butterfly-like tetranuclear clusters as 7-connected nodes, and compund 2 is a 3D net with a different topology. Remarkably, compounds 1 and 2 exhibit selective adsorption of CO2 over N2 and methyl orange (MO) dye molecules. Magnetic measurements reveal that there are antiferromagnetic interactions within the tetranuclear cluster in 1. Furthermore, 2 was well-dispersed in different solvents, and their luminescent properties were investigated, and the results indicated that 2 could be considered as a potential luminescent probe for the detection of ketone molecules.

Health benefit of vegetable/fruit juice-based diet: Role of microbiome.

The gut microbiota is an important contributor to human health. Vegetable/fruit juices provide polyphenols, oligosaccharides, fiber and nitrate (beet juice), which may induce a prebiotic-like effect. Juice-based diets are becoming popular. However, there is a lack of scientific evidence of their health benefits. It was our hypothesis that changes in the intestinal microbiota induced by a juice-based diet play an important role in their health benefits. Twenty healthy adults consumed only vegetable/fruit juices for 3 days followed by 14 days of customary diet. On day 4 we observed a significant decrease in weight and body mass index (p = 2.0E-05), which was maintained until day 17 (p = 3.0E-04). On day 4 the proportion of the phylum Firmicutes and Proteobacteria in stool was significantly decreased and Bacteroidetes and Cyanobacteria was increased compared to baseline and was partially reversed on day 17. On day 4 plasma and urine nitric oxide was increased by 244 ± 89% and 450 ± 360%, respectively, and urinary lipid peroxidation marker malondialdehyde was decreased by 32 ± 21% compared to baseline. General well-being score was increased at the end of the study. In summary a 3-day juice-based diet altered the intestinal microbiota associated with weight loss, increase in the vasodilator NO, and decrease in lipid oxidation.

[Effects of Tengmei Decoction on the PPAR-y/NF-KB Signaling Pathway in Synovium of Collagen-in- duced Arthritis Rats].

Objective To observe the effects of Tengmei Decoction (TMD) on the expressions of peroxisome proliferator activated receptor gamma (PPARγ) , nuclear factor kappa B (NF-κB) , and IL- 17 in synovium of collagen-induced arthritis (CIA) rats, and to study its molecular mechanismpf. inhibi- ting synovial immune inflammatory injuries. Methods CIA model was established in Sprague-Dawley rats. Successfully modeled rats were randomly divided into the model group, the positive drug ,oup, high and low dose TMD groups, 6 in each group. Besides, a normal group was set up (n =6). Deionized water (10 mL . kg⁻¹ . d⁻¹) was administrated to rats in the normal group and the model group by gastro- gavage. Leflunomide (1. 87 mg . kg ⁻¹ . d ⁻¹) was administrated to rats in the positive drug group by gastro- gavage. TMD (31. 8 g crude drugs . kg ⁻¹ . d ⁻¹ and 15. 9 g crude drugs . kg ⁻¹ . d ⁻¹) was administrated to rats in high and low dose TMD groups respectively by gastrogavage. The intervention lasted for 12 suc- cessive weeks. Protein and mRNA levels of PPARy, P65, and IL-17 were detected at the end of intervention. Results Compared with the normal group, mRNA and protein expression levels of PPARγ, P65, and IL-17 were up-regulated in the model group (P <0. 01). Compared with the model group, PPARγ pro- tein expression level was up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in high dose TMD group (P <0. 01). mRNA and protein expression levels of PPARγ were up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in the positive drug group and low dose TMD group (P <0. 01). Conclusions TMD could ameliorate pathological damage of joint synovium , and inhibit expressions of immune inflammatory factors.

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways.

Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI2) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI2 and 15-lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI2 and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre- versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI2 (as measured by 6-keto PGF1α) and 15-HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSE-induced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer. Cancer Prev Res; 9(12); 925-32. ©2016 AACR.

Association of sugary beverages with survival among patients with cancers of the upper aerodigestive tract.

PURPOSE: The role of consumption of added sugars in cancers of the upper aerodigestive tract (UADT) is unclear. We examined associations between sugary beverages and susceptibility to UADT cancer as well as overall survival among UADT cancer patients. METHODS: The association between dietary added sugar and susceptibility to UADT cancers or overall survival among 601 UADT cancer cases was evaluated using data from a population-based case-control study conducted in Los Angeles County. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals (CI) for cancer susceptibility, and Cox regression was used to estimate hazards ratios (HRs) with 95 % CIs for survival, adjusting for relevant confounders. RESULTS: A total of 248 deaths were observed during follow-up (median 12.1 years). A positive association was observed with consumption of grams of sugar from beverages, including soft drinks and fruit juices, and poorer survival among UADT cancer cases (aHR, Q4 vs. Q1:1.88; 95 % CI 1.29, 2.72; p for trend = 0.002), as well as servings of sugary beverages (aHR, Q4 vs. Q1: 95 % CI 1.97, 95 % CI 1.32-2.93). This was due largely to consumption of sugars from soft drinks. Particularly, high consumption of sugary beverages was associated with poorer survival among esophageal cancer cases, driven by squamous cancers. No association was observed between sugary beverages and cancer susceptibility. CONCLUSION: These findings suggest that consumption of sugary beverages may decrease survival associated with UADT cancers. Additional studies should be conducted to examine survival among cancer patients consuming high amounts of added or refined sugars. Such studies may highlight prognostic factors for UADT cancers.