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| 2. |
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| 3. |
- Berger, Karoline, 1991, et al.
(författare)
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Reduction of Progranulin-Induced Breast Cancer Stem Cell Propagation by Sortilin-Targeting Cyclotriazadisulfonamide (CADA) Compounds
- 2021
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:17, s. 12865-12876
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotriazadisulfonamide (CADA) compounds selectively down- modulate two human proteins of potential therapeutic interest, cluster of differentiation 4 (CD4) and sortilin. Progranulin is secreted from some breast cancer cells, causing dedifferentiation of receiving cancer cells and cancer stem cell proliferation. Inhibition of progranulin binding to sortilin, its main receptor, can block progranulin-induced metastatic breast cancer using a triple-negative in vivo xenograft model. In the current study, seven CADA compounds (CADA, VGD020, VGD071, TL020, TL023, LAL014, and DJ010) were examined for reduction of cellular sortilin expression and progranulin-induced breast cancer stem cell propagation. In addition, inhibition of progranulin-induced mammosphere formation was examined and found to be most significant for TL020, TL023, VGD071, and LAL014. Full experimental details are given for the synthesis and characterization of the four new compounds (TL020, TL023, VGD071, and DJ010). Comparison of solubilities, potencies, and cytotoxicities identified VGD071 as a promising candidate for future studies using mouse breast cancer models.
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| 4. |
- Kyro, C., et al.
(författare)
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ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
- 2013
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 1207-1208
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: Few studies have investigatedthe association between whole-grain intake and colorectal cancer.Whole-grain products are one of the dietary items proneto measurement errors, making the use of objective measures,such as biomarkers, highly relevant. The objective of the studywas to investigate the association between biomarkers ofwhole-grain intake, alkylresorcinols, and colorectal cancer ina nested case-control study within the European ProspectiveInvestigation into Cancer and Nutrition (EPIC). Methods: We included 1372 first incident colorectal cancercases and 1372 individually matched controls and calculatedthe incidence rate ratios (IRR) for overall and sub-sites of colorectalcancer using conditional logistic regression adjusted forpotential confounders.Results: Plasma total alkylresorcinol concentrations werenot associated with risk of overall colorectal cancer, proximalcolon cancer or rectal cancer. However, high plasma total alkylresorcinolconcentrations were statistically significantly associatedwith lower incidence of cancer located in the distal (leftor descending) part of the colon. Adjusted IRR of distal coloncancer for highest versus lowest quartile of plasma alkylresorcinolwas 0.48 (95% confidence interval = 0.28 to 0.83). Furthermore,we observed an inverse association with colon cancerfor the Scandinavian part of the participants. Alkylresorcinolsmay be more appropriate as biomarkers in Middle Europe andScandinavia i.e. in areas where whole grains are regularly consumed.Conclusions: Whole-grain intake, assessed by alkylresorcinols,was associated with a lower incidence of distal coloncancer. Alkylresorcinols seem useful as objective biomarkersof whole-grain intake in populations where whole-grains are astaple part of the diet. Acknowledgements: This work was supportedby World Cancer Research Fund International (WCRF)and WCRF Netherlands (WCRF NL) (2011/436), and NordForsk(Centre of Excellence programme HELGA (070015)).
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| 6. |
- Munch Roager, Henrik, et al.
(författare)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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| 7. |
- Kvaerner, A. S., et al.
(författare)
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The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
- 2021
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.
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| 8. |
- Laslett, Anne-Marie, et al.
(författare)
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A Multi-Country Study of Harms to Children Because of Others' Drinking
- 2017
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 78:2, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aims to ascertain and compare the prevalence and correlates of alcohol-related harms to children cross nationally. Method: National and regional sample surveys of randomly selected households included 7,848 carers (4,223 women) from eight countries (Australia, Chile, Ireland, Lao People's Democratic Republic [PDR], Nigeria, Sri Lanka, Thailand, and Vietnam). Country response rates ranged from 35% to 99%. Face-to-face or telephone surveys asking about harm from others' drinking to children ages 0-17 years were conducted, including four specific harms: that because of others' drinking in the past year children had been (a) physically hurt, (b) verbally abused, (c) exposed to domestic violence, or (d) left unsupervised. Results: The prevalence of alcohol-related harms to children varied from a low of 4% in Lao PDR to 14% in Vietnam. Alcohol-related harms to children were reported by a substantial minority of families in most countries, with only Lao PDR and Nigeria reporting significantly lower levels of harm. Alcohol-related harms to children were dispersed sociodemographically and were concentrated in families with heavy drinkers. Conclusions: Family-level drinking patterns were consistently identified as correlates of harm to children because of others' drinking, whereas sociodemographic factors showed few obvious correlations.
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| 9. |
- Monfort-Pires, M., et al.
(författare)
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Serum short-chain fatty acids are associated with brown adipose tissue metabolism in humans
- 2023
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Ingår i: Diabetologia. - 1432-0428 .- 0012-186X. ; 66:SUPPL 1, s. S297-S298
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Short-chain fatty acids (SCFAs) result from the fermentation of dietary fibre in the colon and are shown to play an important role in energy metabolism. The relationship between circulating SCFA and brown adipose tissue (BAT) in humans remains to be clarified. We investigated the associations between circulating SCFA and BAT function in humans.
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| 10. |
- Skeie, G., et al.
(författare)
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Intake of whole grains and incidence of gastric and oesophageal cancer in the HELGA cohort
- 2013
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 198-199
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: Whole grains are a good sourceof dietary fibre, but beneficial effects might also stem fromother components of the grain. Very few studies exist on intakeof whole grains and incidence of stomach and oesophagealcancer, but studies on dietary fibre and these cancers suggesta protective effect. The objective of this work was to study theassociation between intake of whole grains and incidence ofoesophageal and gastric cancer. Methods: The Helga cohort has 120 000 participants fromthe Norwegian Women and Cancer study, The Northern Sweden Health and Disease study and the Danish Diet, Cancerand Health study, recruited in 1992-1999. After exclusions, 112cases of oesophageal cancer, 185 cases of gastric cancer and 113700 other cohort members were included in the analyses. Theyprovided dietary information in semi-quantitative FFQs at baseline,and also information about other risk factors. Cancer information was obtained by linkage to the respective cancerregistries. The association between whole grain intake and cancerwas analysed with Cox proportional hazards models. Results: The median whole-grain intake was 47.4 g/day(5th-95th percentile: 13.3-101.1) in the non-cases, 37.5 g/day(10.8-87.2) in oesophageal cancer cases, and 45.1 g/day (8.1-99.1) in gastric cancer cases. A decreased risk of oesophagealcancer was observed, HR=0.83 (CI 0.69-0.99) p=0.04 per 20g of whole grains. The HR for highest compared with lowesttertile of intake was 0.56 (0.32-0.97) p=0.03. The analyses wereadjusted for country, smoking status, age at baseline, sex, processedmeat, alcohol and vitamin C. No association was foundfor whole grains and gastric cancer.Conclusion: In this study, higher intake of whole grains wasassociated with lower risk of oesophageal cancer. Acknowledgements: This work was supported by NordForsk– Centre of excellence programme HELGA (070015).
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| 11. |
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| 12. |
- Andersson, Daniel, 1979, et al.
(författare)
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Properties of targeted preamplification in DNA and cDNA quantification
- 2015
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Ingår i: Expert Review of Molecular Diagnostics. - : Informa UK Limited. - 1473-7159 .- 1744-8352. ; 15:8, s. 1085-1100
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Forskningsöversikt (refereegranskat)abstract
- Objective: Quantification of small molecule numbers often requires preamplification to generate enough copies for accurate downstream enumerations. Here, we studied experimental parameters in targeted preamplification and their effects on downstream quantitative real-time PCR (qPCR). Methods: To evaluate different strategies, we monitored the preamplification reaction in real-time using SYBR Green detection chemistry followed by melting curve analysis. Furthermore, individual targets were evaluated by qPCR. Result: The preamplification reaction performed best when a large number of primer pairs was included in the primer pool. In addition, preamplification efficiency, reproducibility and specificity were found to depend on the number of template molecules present, primer concentration, annealing time and annealing temperature. The amount of nonspecific PCR products could also be reduced about 1000-fold using bovine serum albumin, glycerol and formamide in the preamplification. Conclusion: On the basis of our findings, we provide recommendations how to perform robust and highly accurate targeted preamplification in combination with qPCR or next-generation sequencing.
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| 14. |
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| 15. |
- Bruce, Benjamin, et al.
(författare)
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Expression of the cytoskeleton linker protein ezrin in human cancers
- 2007
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Ingår i: Clinical and Experimental Metastasis. - : Springer Science and Business Media LLC. - 1573-7276 .- 0262-0898. ; 24:2, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the metastasis-associated protein, ezrin, in over 5,000 human cancers and normal tissues was analyzed using tissue microarray immunohistochemistry. Ezrin staining was compared between cancers and their corresponding normal tissues, between cancers of epithelial and mesenchymal origin, in the context of the putative inhibitor protein, merlin, and against clinicopathological data available for breast, lung, prostate cancers and sarcomas. Ezrin was found in most cancers and normal tissues at varying levels of intensity. In general ezrin was expressed at higher levels in sarcomas than in carcinomas. By normalizing the expression of ezrin in each cancer using ezrin expression found in the corresponding normal tissue, significant associations between ezrin were found in advancing histological grade in sarcomas (P = 0.02) and poor outcome in breast cancer (P = 0.025). Clinicopathologic associations were not changed by simultaneous assessment of ezrin and merlin in each patient sample for the cancer types examined. These data support a role for ezrin in the biology of human cancers and the need for additional studies in breast cancer and sarcoma patients that may validate ezrin as a marker of cancer progression and as a potential target for cancer therapy.
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| 16. |
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| 17. |
- Damsgaard, Camilla T, et al.
(författare)
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Associations between school meal-induced dietary changes and metabolic syndrome markers in 8-11-year-old Danish children.
- 2016
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 55:5, s. 1973-84
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that provision of Nordic school meals rich in fish, vegetables and potatoes and with reduced intakes of fat improved blood pressure, insulin resistance assessed by the homeostatic model (HOMA-IR), and plasma triacylglycerol despite increasing waist circumference in Danish 8-11-year-olds. This study explored whether intake or biomarkers of key dietary components in the schools meals were associated with these metabolic syndrome (MetS) markers during the 6-month intervention.
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| 18. |
- Damsgaard, Camilla T, et al.
(författare)
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Whole-Grain Intake, Reflected by Dietary Records and Biomarkers, Is Inversely Associated with Circulating Insulin and Other Cardiometabolic Markers in 8- to 11-Year-Old Children.
- 2017
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 147:5, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-grain consumption seems to be cardioprotective in adults, but evidence in children is limited.Objective: We investigated whether intakes of total whole grain and dietary fiber as well as specific whole grains were associated with fat mass and cardiometabolic risk profile in children.Methods: We collected cross-sectional data on parental education, puberty, diet by 7-d records, and physical activity by accelerometry and measured anthropometry, fat mass index by dual-energy X-ray absorptiometry, and blood pressure in 713 Danish children aged 8-11 y. Fasting blood samples were obtained and analyzed for alkylresorcinols, biomarkers of whole-grain wheat and rye intake, HDL and LDL cholesterol, triacylglycerols, insulin, and glucose. Linear mixed models included puberty, parental education, physical activity, and intakes of energy, fruit and vegetables, saturated fat, and n-3 (ω-3) polyunsaturated fatty acids.Results: Median (IQR) whole-grain and dietary fiber intakes were 52 g/d (35-72 g/d) and 17 g/d (14-22 g/d), respectively. Fourteen percent of children were overweight or obese and most had low-risk cardiometabolic profiles. Dietary whole-grain and fiber intakes were not associated with fat mass index but were inversely associated with serum insulin [both P
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| 19. |
- Daskova, Nikola, et al.
(författare)
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Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial
- 2023
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Ingår i: Nutrition and Diabetes. - 2044-4052. ; 13:1, s. 7-
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.
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| 20. |
- Holm, C, et al.
(författare)
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Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer
- 2009
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Ingår i: JOURNAL OF PATHOLOGY. - : Wiley. - 0022-3417 .- 1096-9896. ; 217:3, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylation of oestrogen receptor a at serine 305 (ER alpha S305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ER alpha S305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ER alpha S305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ER alpha S305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ER alpha S305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ER alpha S305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ER alpha S305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ER alpha S305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup.
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| 21. |
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| 22. |
- Jönsson, Christina, et al.
(författare)
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Biocatalysis in the Recycling Landscape for Synthetic Polymers and Plastics towards Circular Textiles
- 2021
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Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 14:19, s. 4028-4040
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Tidskriftsartikel (refereegranskat)abstract
- Although recovery of fibers from used textiles with retained material quality is desired, separation of individual components from polymer blends used in today's complex textile materials is currently not available at viable scale. Biotechnology could provide a solution to this pressing problem by enabling selective depolymerization of recyclable fibers of natural and synthetic origin, to isolate constituents or even recover monomers. We compiled experimental data for biocatalytic polymer degradation with a focus on synthetic polymers with hydrolysable links and calculated conversion rates to explore this path The analysis emphasizes that we urgently need major research efforts: beyond cellulose-based fibers, biotechnological-assisted depolymerization of plastics so far only works for polyethylene terephthalate, with degradation of a few other relevant synthetic polymer chains being reported. In contrast, by analyzing market data and emerging trends for synthetic fibers in the textile industry, in combination with numbers from used garment collection and sorting plants, it was shown that the use of difficult-to-recycle blended materials is rapidly growing. If the lack of recycling technology and production trend for fiber blends remains, a volume of more than 3400 Mt of waste will have been accumulated by 2030. This work highlights the urgent need to transform the textile industry from a biocatalytic perspective.
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| 23. |
- Keune, Willem-Jan, et al.
(författare)
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Low PIP4K2B Expression in Human Breast Tumors Correlates with Reduced Patient Survival: A Role for PIP4K2B in the Regulation of E-Cadherin Expression
- 2013
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Ingår i: Cancer Research. - 1538-7445. ; 73:23, s. 6913-6925
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Tidskriftsartikel (refereegranskat)abstract
- Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase beta (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P-2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan-Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-beta-induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-beta-induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival. (C)2013 AACR.
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