Artykuły w czasopismach na temat „Invasive phenotypes”
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Mareel, Marc M., Frans M. Van Roy i Patrick De Baetselier. "The invasive phenotypes". Cancer and Metastasis Reviews 9, nr 1 (lipiec 1990): 45–62. http://dx.doi.org/10.1007/bf00047588.
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Golmohammadi, Rahim, Mohammad Reza Mohajeri, Alireza Mosavi Jarrahi, Ali Reza Moslem, Akbar Pejhan i Ali Gohari. "Histopathologic Characteristics of Invasive and Non-invasive Ductal Tumors have Relationship with Different Phenotypes of ER / PR Receptors in Breast Cancer Patients". Asian Pacific Journal of Cancer Biology 6, nr 3 (9.07.2021): 181–85. http://dx.doi.org/10.31557/apjcb.2021.6.3.181-185.
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Objective: Contradictory reports have been published regarding the expression levels of the hormone receptors of estrogen and progesterone (ER / PR) and theirclinical importance in diagnosis of breast cancer. The aim of this study was to evaluate the relationship between pathological features of invasive and non-invasive ductal tumors by different ER / PR phenotypes. Methods: This descriptive-analytical study was performed on 74 specimens of breast cancer referred to Isfahan Hospitals for diagnosis between 2015 - 2018. After fixation of the specimens in formalin, tissue passage, cross section and H / E staining, the specimens were divided into two groups: non- invasive and Invasive ductal Carcinoma. After removing of mask, expression of different ER / PR phenotypes was performed using primary monoclonal antibody and immunohistochemically methods. Results: From 74 malignant specimens, 61 (82.4%) were in the category of invasive ductal tumors and 13 cases (17.6%) were in the category of non-invasive ductal tumors. Out of 73 patients with positive ER or PR phenotype 47 samples (63.5%) had ER + / PR +phenotypes, 6 samples had (8.1%) ER+ / PR –phenotype, 20 samples (27%) had ER- / PR + phenotype and only one sample (1.4%) had the ER- / PR- phenotype and was in the category of invasive ductal tumors. There was not detected ER- / PR- phenotype expression in non-invasive ductal tumor. Further analysis showed that there were not significant difference between ER / PR phenotype and tumor stage (p =0.36) or with tumor Grade (P=0.38), high age of menopause or post menopause (P> 0.05). Conclusion: Our data shows that expression of ER- / PR- phenotype only was detected in invasive ductal tumor. It is thought that the tumor type maybe affects the expression of different types of ER / PR hormone receptor phenotypes in breast cancer patients.
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Mukhopadhyay, Utpal K., Patrick Mooney, Lilly Jia, Robert Eves, Leda Raptis i Alan S. Mak. "Doubles Game: Src-Stat3 versus p53-PTEN in Cellular Migration and Invasion". Molecular and Cellular Biology 30, nr 21 (23.08.2010): 4980–95. http://dx.doi.org/10.1128/mcb.00004-10.
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ABSTRACT We have recently shown that Src induces the formation of podosomes and cell invasion by suppressing endogenous p53, while enhanced p53 strongly represses the Src-induced invasive phenotype. However, the mechanism by which Src and p53 play antagonistic roles in cell invasion is unknown. Here we show that the Stat3 oncogene is a required downstream effector of Src in inducing podosome structures and related invasive phenotypes. Stat3 promotes Src phenotypes through the suppression of p53 and the p53-inducible protein caldesmon, a known podosome antagonist. In contrast, enhanced p53 attenuates Stat3 function and Src-induced podosome formation by upregulating the tumor suppressor PTEN. PTEN, through the inactivation of Src/Stat3 function, also stabilizes the podosome-antagonizing p53/caldesmon axis, thereby further enhancing the anti-invasive potential of the cell. Furthermore, the protein phosphatase activity of PTEN plays a major role in the negative regulation of the Src/Stat3 pathway and represses podosome formation. Our data suggest that cellular invasiveness is dependent on the balance between two opposing forces: the proinvasive oncogenes Src-Stat3 and the anti-invasive tumor suppressors p53-PTEN.
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Zhang, Luna, Anqun Chen, Yanjiao Li, Duohui Li, Shiping Cheng, Liping Cheng i Yinzhan Liu. "Differences in Phenotypic Plasticity between Invasive and Native Plants Responding to Three Environmental Factors". Life 12, nr 12 (25.11.2022): 1970. http://dx.doi.org/10.3390/life12121970.
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The phenotypic plasticity hypothesis suggests that exotic plants may have greater phenotypic plasticity than native plants. However, whether phenotypic changes vary according to different environmental factors has not been well studied. We conducted a multi-species greenhouse experiment to study the responses of six different phenotypic traits, namely height, leaf number, specific leaf area, total biomass, root mass fraction, and leaf mass fraction, of native and invasive species to nutrients, water, and light. Each treatment was divided into two levels: high and low. In the nutrient addition experiment, only the leaf mass fraction and root mass fraction of the plants supported the phenotypic plasticity hypothesis. Then, none of the six traits supported the phenotypic plasticity hypothesis in the water or light treatment experiments. The results show that, for different environmental factors and phenotypes, the phenotypic plasticity hypothesis of plant invasion is inconsistent. When using the phenotypic plasticity hypothesis to explain plant invasion, variations in environmental factors and phenotypes should be considered.
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Pershing, Nicole L., Aurélie Kapusta, Shannon Nielsen, Hillary Crandall, E. Kent Korgenski, Carrie L. Byington, Krow Ampofo i Anne J. Blaschke. "#64: An odyssey Beyond the Capsule: Genetic Determinants of Pediatric Invasive Streptococcus pneumoniae Empyema". Journal of the Pediatric Infectious Diseases Society 10, Supplement_1 (1.03.2021): S7. http://dx.doi.org/10.1093/jpids/piaa170.021.
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Abstract Background Streptococcus pneumoniae is among the most common causes of invasive bacterial infections in children, including pneumonia, bacteremia, and meningitis. Over 90 different serotypes (ST) of pneumococcus exist, with enrichment of some ST within specific invasive phenotypes. Other than capsular genes, molecular determinants of particular invasive phenotypes remain largely unknown. Although vaccination targeting especially invasive ST capsular antigens has successfully decreased the incidence of invasive pneumococcal disease (IPD), new ST have emerged, suggesting methods to target other aspects of pneumococcal invasiveness are needed. Methods Pneumococcal isolates from IPD were collected from children presenting to Primary Children’s Hospital from 1996–2018. All viable isolates underwent next-generation sequencing (Illumina), quality control filtering for contamination and low coverage, de novo genome assembly with SPADES, and annotation with PROKKA. Clinical phenotypes were manually validated with physician chart review. Isolates were serotyped via Quelling and in silico using SeroBA. ROARY was used for pan-genome assembly, and SCOARY for microbial genome-wide association studies. RAxML was used for phylogenetic analysis. Results A total of 354 viable pneumococcal isolates were available for genomic analysis including a spectrum of invasive phenotypes: pneumonia (n = 138, of which 54 were complicated by empyema), CNS infection (n = 50), SSTI/bone infections (n = 42), and isolated bacteremia (n = 68). Thirteen samples were censored for poor coverage or genetic contamination. Invasive isolates spanned 37 capsular ST. The pneumococcal pan-genome comprised 6462 genes, of which only 23% were shared by at least 99% of samples. Phylogenetic relatedness resulted in clustering of some ST (e.g., ST1, ST3), whereas others (eg ST19A) were more broadly distributed. Empyema and meningitis phenotypes were distributed across the phylogenetic tree, but enriched in distinct clusters that crossed ST clusters. Genes involved in empyemagenic pneumococcal capsule production, and those implicated in sensing of preferred sugars or non-preferred sugar metabolism were statistically correlated with the empyema phenotype. Conclusion There is marked genetic diversity among invasive pneumococcal isolates, potentially contributing to the variability of disease phenotypes observed. Clustering of invasive phenotypes across ST suggests a genetic signature for invasive phenotypes other than capsule genes alone, further supported by enrichment of specific genes associated with alternative sugar metabolism in empyema isolates. Critical determinants of invasive phenotypes will inform future efforts at disease prevention and treatment.
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Bultemeier, Brett W., Mike D. Netherland, Jason A. Ferrell i William T. Haller. "Differential Herbicide Response among Three Phenotypes ofCabomba caroliniana". Invasive Plant Science and Management 2, nr 4 (październik 2009): 352–59. http://dx.doi.org/10.1614/ipsm-09-035.1.
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AbstractCabomba is a submersed aquatic plant native to the southeastern United States that is commonly sold worldwide through the aquarium trade. While infrequently managed in its native range, cabomba has recently been reported as invasive and tolerant to management efforts in the northern areas of the United States and in other countries. Invasive populations of cabomba are characterized by a phenotype that is bright green. In contrast, cabomba native to the southeastern United States is characterized by a red phenotype, while plants sold through the aquarium trade have intermediate characteristics of both the green and red phenotypes. The response of the three cabomba phenotypes to selected herbicides was evaluated by measuring photosynthetic response over the course of a static 144-hr exposure. Plants were exposed to the maximum recommended use-rates of 2,4-D, carfentrazone, copper, diquat, endothall (amine and dipotasium salt formulation), flumioxazin, quinclorac, triclopyr, and a combination of diquat and copper. A submersed plant species known to be sensitive to each of these herbicides was also included to compare photosynthetic response of the cabomba to a susceptible plant. The photosynthetic response of the red and green phenotypes differed following exposure to carfentrazone, diquat, 2,4-D, triclopyr, and flumioxazin. Diquat, diquat plus copper, endothall (amine salt), and flumioxazin were the only products that resulted in a greater than 50% reduction of photosynthesis in all three phenotypes of cabomba. A second experiment was conducted where all three phenotypes of cabomba were exposed to these four herbicides for 24 hr, and photosynthesis was evaluated. Following the 24-hr exposure, results further documented distinct response differences between the green and red phenotypes, with the green phenotype demonstrating a reduced sensitivity to the herbicides evaluated. Results demonstrate clear phenotypic differences in response to herbicide treatments and lack of susceptibility of cabomba to most herbicides.
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Gajic, Ina, Natasa Opavski, Vera Mijac i L. Ranin. "Macrolide-resistant phenotypes of invasive streptococcus pneumoniae isolates in Serbia". Archives of Biological Sciences 64, nr 4 (2012): 1377–82. http://dx.doi.org/10.2298/abs1204377g.
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Macrolide resistance in Streptococcus pneumoniae has emerged as an important worldwide problem over the past decade. The aim of this study was to investigate macrolide-resistant phenotypes and the antimicrobial susceptibility patterns of invasive pneumococci in Serbia. A total of 68 invasive pneumococcal strains, collected from 2009 to 2011, were sent from regional laboratories to the National Reference Laboratory. Susceptibility testing was performed using the VITEK2 system and phenotypes were determined by triple-test. Overall penicillin and erythromycin nonsusceptibility rates were 26% and 43%, respectively. Resistance rates were higher in children than in adults. Co-resistance to penicillin and erythromycin was detected in 18% strains. Resistance rates to the third generation of cephalosporins, TMP-SXT and tetracycline were 16%, 37% and 29%, respectively. All isolates were fully susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin. Twenty-two isolates (79%) an expressed macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype and M phenotype was found in 21% of macrolide resistant strains.
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ANDERSEN, J., L. BERTHELSEN, B. BECH JENSEN i I. LIND. "Dynamics of the meningococcal carrier state and characteristics of the carrier strains: a longitudinal study within three cohorts of military recruits". Epidemiology and Infection 121, nr 1 (sierpień 1998): 85–94. http://dx.doi.org/10.1017/s0950268898008930.
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Three cohorts of Danish male military recruits (n=1069) were studied for pharyngeal meningococcal carriage during 3 months at different seasons: 39–47% of entrants were meningococcal carriers and the carriage rate remained constant over time and season. However, individual changes in the carrier state occurred frequently, and after 3 months 34% had changed carrier state on one or more occasions. Initially, a loss of carriage predominated; on the other hand almost 20% of non-carriers had acquisition of meningococci within the first month. The serological phenotypes of the 670 carrier strains were compared with those of 261 invasive strains recovered concurrently from patients with meningococcal disease country-wide. Both carrier strains and invasive strains were phenotypically heterogeneous. Almost 60% of the invasive strains belonged to three phenotypes: B[ratio ]15[ratio ]P1.7, 16, C[ratio ]2a[ratio ]P1.2, 5 and C[ratio ]2b[ratio ]P1.2, 5. In contrast, these phenotypes only amounted to 3·2% of the carrier strains, among which no phenotype was found with a prevalence above 4·9%. However, 30% of the carrier strains had serological phenotypes identical to those of 80% of the invasive strains. Our results indicated that the transmission rate of potential pathogenic carrier strains did not differ from that of other carrier strains.
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Gajić, Ina, Miloš Marković, Dušan Kekić, Sunčica Popović, Vera Mijač, Lazar Ranin i Nataša Opavski. "Serotypes and antimicrobial susceptibility of invasive 'Streptococcus pneumoniae' isolated in Serbia in 2012-2013". Medicinska istrazivanja 50, nr 2 (2016): 49–53. http://dx.doi.org/10.5937/medist1602049g.
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The aim of this study was to: determine susceptibility patterns of invasive Streptococcus pneumoniae to antimicrobial agents, evaluate macrolide resistance phenotypes and genotypes and identify capsular serotypes among invasive isolates of S. pneumoniae circulating in Serbia. The total of 85 invasive pneumococcal strains, collected during 2012 and 2013, were sent from regional laboratories to the National Reference Laboratory. Susceptibility testing was performed by disk diffusion and E test, while phenotypes and genotypes of macrolide resistant strains were determined by double-test and PCR, respectively. Serotyping was performed by Quelling reaction. The overall penicillin and erythromycin non-susceptibility rates were 14.12% and 28.23%, respectively. Resistance rates were significantly higher in children than in adults and (p<0,01). Co-resistance to penicillin and erythromycin was detected in 7.06% strains. Resistance rates to tetracycline and chloramphenicol were 29.41% and 15.29%, respectively. The rate of multi resistance was 27.06%. cMLS phenotype was detected in 62.5% of all macrolide resistant isolates, while 37.5% expressed M phenotype. All 15 isolates with cMLS phenotype harbored ermB gene and all M isolates harbored mefA. The most common resistant serotypes were 3, 9A and 23F. This study revealed that penicillin and macrolide resistance among invasive pneumococcal isolates is high. Obtained results emphasize the need for continuous monitoring of invasive pneumococcal disease in Serbia.
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Nicotra, Adrienne B., i Amy Davidson. "Adaptive phenotypic plasticity and plant water use". Functional Plant Biology 37, nr 2 (2010): 117. http://dx.doi.org/10.1071/fp09139.
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The emergence of new techniques in plant science, including molecular and phenomic tools, presents a novel opportunity to re-evaluate the way we examine the phenotype. Our increasing capacity for phenotyping means that not only can we consider increasing numbers of species or varieties, but also that we can effectively quantify the phenotypes of these different genotypes under a range of environmental conditions. The phenotypic plasticity of a given genotype, or the range of phenotypes, that can be expressed dependent upon environment becomes something we can feasibly assess. Of particular importance is phenotypic variation that increases fitness or survival – adaptive phenotypic plasticity. Here, we examine the case of adaptive phenotypic plasticity in plant water use traits and consider how taking an ecological and evolutionary perspective on plasticity in these traits might have relevance for agriculture, horticulture and the management of native and invasive plant species in an era of rapid climate change.
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Vandermeulen, Matthew D., i Paul J. Cullen. "Gene by Environment Interactions reveal new regulatory aspects of signaling network plasticity". PLOS Genetics 18, nr 1 (4.01.2022): e1009988. http://dx.doi.org/10.1371/journal.pgen.1009988.
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Phenotypes can change during exposure to different environments through the regulation of signaling pathways that operate in integrated networks. How signaling networks produce different phenotypes in different settings is not fully understood. Here, Gene by Environment Interactions (GEIs) were used to explore the regulatory network that controls filamentous/invasive growth in the yeast Saccharomyces cerevisiae. GEI analysis revealed that the regulation of invasive growth is decentralized and varies extensively across environments. Different regulatory pathways were critical or dispensable depending on the environment, microenvironment, or time point tested, and the pathway that made the strongest contribution changed depending on the environment. Some regulators even showed conditional role reversals. Ranking pathways’ roles across environments revealed an under-appreciated pathway (OPI1) as the single strongest regulator among the major pathways tested (RAS, RIM101, and MAPK). One mechanism that may explain the high degree of regulatory plasticity observed was conditional pathway interactions, such as conditional redundancy and conditional cross-pathway regulation. Another mechanism was that different pathways conditionally and differentially regulated gene expression, such as target genes that control separate cell adhesion mechanisms (FLO11 and SFG1). An exception to decentralized regulation of invasive growth was that morphogenetic changes (cell elongation and budding pattern) were primarily regulated by one pathway (MAPK). GEI analysis also uncovered a round-cell invasion phenotype. Our work suggests that GEI analysis is a simple and powerful approach to define the regulatory basis of complex phenotypes and may be applicable to many systems.
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Suwannakul, S., G. P. Stafford, S. A. Whawell i C. W. I. Douglas. "Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion". Microbiology 156, nr 10 (1.10.2010): 3052–64. http://dx.doi.org/10.1099/mic.0.038075-0.
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Bistable populations of bacteria give rise to two or more subtypes that exhibit different phenotypes. We have explored whether the periodontal pathogen Porphyromonas gingivalis exhibits bistable invasive phenotypes. Using a modified cell invasion assay, we show for the first time that there are two distinct subtypes within a population of P. gingivalis strains NCTC 11834 and W50 that display differences in their ability to invade oral epithelial cells. The highly invasive subtype invades cells at 10–30-fold higher levels than the poorly invasive subtype and remains highly invasive for approximately 12–16 generations. Analysis of the gingipain activity of these subtypes revealed that the highly invasive type had reduced cell-associated arginine-specific protease activity. The role of Arg-gingipain activity in invasion was verified by enhancement of invasion by rgpAB mutations and by inclusion of an Arg-gingipain inhibitor in invasion assays using wild-type bacteria. In addition, a population of ΔrgpAB bacteria did not contain a hyperinvasive subtype. Screening of the protease activity of wild-type populations of both strains identified high and low protease subtypes which also showed a corresponding reduction or enhancement, respectively, of invasive capabilities. Microarray analysis of these bistable populations revealed a putative signature set of genes that includes oxidative stress resistance and iron transport genes, and which might be critical to invasion of or survival within epithelial cells.
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Shelley, Greg, Jinlu Dai, Jill M. Keller i Evan T. Keller. "Pheno-SELEX: Engineering Anti-Metastatic Aptamers through Targeting the Invasive Phenotype Using Systemic Evolution of Ligands by Exponential Enrichment". Bioengineering 8, nr 12 (13.12.2021): 212. http://dx.doi.org/10.3390/bioengineering8120212.
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Multiple methods (e.g., small molecules and antibodies) have been engineered to target specific proteins and signaling pathways in cancer. However, many mediators of the cancer phenotype are unknown and the ability to target these phenotypes would help mitigate cancer. Aptamers are small DNA or RNA molecules that are designed for therapeutic use. The design of aptamers to target cancers can be challenging. Accordingly, to engineer functionally anti-metastatic aptamers we used a modification of systemic evolution of ligands by exponential enrichment (SELEX) we call Pheno-SELEX to target a known phenotype of cancer metastasis, i.e., invasion. A highly invasive prostate cancer (PCa) cell line was established and used to identify aptamers that bound to it with high affinity as opposed to a less invasive variant to the cell line. The anti-invasive aptamer (AIA1) was found to inhibit in vitro invasion of the original highly invasive PCa cell line, as well as an additional PCa cell line and an osteosarcoma cell line. AIA1 also inhibited in vivo development of metastasis in both a PCa and osteosarcoma model of metastasis. These results indicate that Pheno-SELEX can be successfully used to identify aptamers without knowledge of underlying molecular targets. This study establishes a new paradigm for the identification of functional aptamers.
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Schubert, W., M. Friedenberger, R. Haars, M. Bode, L. Philipsen, T. Nattkemper i H. Ritter. "Automatic Recognition of Muscle-Invasive T-Lymphocytes Expressing Dipeptidyl-Peptidase IV (CD26) and Analysis of the Associated Cell Surface Phenotypes". Journal of Theoretical Medicine 4, nr 1 (2002): 67–74. http://dx.doi.org/10.1080/10273660290015189.
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A neural cell detection system (NCDS) for the automatic quantitation of fluorescent lymphocytes in tissue sections was used to analyze CD26 expression in muscle-invasive T-cells. CD26 is a cell surface dipeptidyl-peptidase IV (DPP IV) involved in co-stimulatory activation of T-cells and also in adhesive events. The NCDS system acquires visual knowledge from a set of training cell image patches selected by a user. The trained system evaluates an image in 2 min calculating (i) the number, (ii) the positions and (iii) the phenotypes of the fluorescent cells. In the present study we have used the NCDS to identity DPP IV (CD26) expressing invasive lymphocytes in sarcoid myopathy and to analyze the associated cell surface phenotypes. We find highly unusual phenotypes characterized by differential combination of seven cell surface receptors usually involved in co-stimulatory events in T-lymphocytes. The data support a differential adhesive rather than a co-stimulatory role of CD26 in muscle-invasive cells. The adaptability of the NCDS algorithm to diverse types of cells should enable us to approach any invasion process, including invasion of malignant cells.
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Clarke, R., N. Brünner, E. W. Thompson, P. Glanz, D. Katz, R. B. Dickson i M. E. Lippman. "The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer". Journal of Endocrinology 122, nr 1 (lipiec 1989): 331–40. http://dx.doi.org/10.1677/joe.0.1220331.
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ABSTRACT Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisition of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours. Journal of Endocrinology (1989) 122, 331–340
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de Figueiredo, Catarina M., Daniella H. Hock, Débora Trichez, Maria de Lourdes B. Magalhães, Mario L. Lopes, Henrique V. de Amorim i Boris U. Stambuk. "High Foam Phenotypic Diversity and Variability in Flocculant Gene Observed for Various Yeast Cell Surfaces Present as Industrial Contaminants". Fermentation 7, nr 3 (24.07.2021): 127. http://dx.doi.org/10.3390/fermentation7030127.
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Many contaminant yeast strains that survive inside fuel ethanol industrial vats show detrimental cell surface phenotypes. These harmful effects may include filamentation, invasive growth, flocculation, biofilm formation, and excessive foam production. Previous studies have linked some of these phenotypes to the expression of FLO genes, and the presence of gene length polymorphisms causing the expansion of FLO gene size appears to result in stronger flocculation and biofilm formation phenotypes. We performed here a molecular analysis of FLO1 and FLO11 gene polymorphisms present in contaminant strains of Saccharomyces cerevisiae from Brazilian fuel ethanol distilleries showing vigorous foaming phenotypes during fermentation. The size variability of these genes was correlated with cellular hydrophobicity, flocculation, and highly foaming phenotypes in these yeast strains. Our results also showed that deleting the primary activator of FLO genes (the FLO8 gene) from the genome of a contaminant and highly foaming industrial strain avoids complex foam formation, flocculation, invasive growth, and biofilm production by the engineered (flo8∆::BleR/flo8Δ::kanMX) yeast strain. Thus, the characterization of highly foaming yeasts and the influence of FLO8 in this phenotype open new perspectives for yeast strain engineering and optimization in the sugarcane fuel-ethanol industry.
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Essay, Patrick, Jarrod Mosier i Vignesh Subbian. "Rule-Based Cohort Definitions for Acute Respiratory Failure: Electronic Phenotyping Algorithm". JMIR Medical Informatics 8, nr 4 (15.04.2020): e18402. http://dx.doi.org/10.2196/18402.
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Background Acute respiratory failure is generally treated with invasive mechanical ventilation or noninvasive respiratory support strategies. The efficacies of the various strategies are not fully understood. There is a need for accurate therapy-based phenotyping for secondary analyses of electronic health record data to answer research questions regarding respiratory management and outcomes with each strategy. Objective The objective of this study was to address knowledge gaps related to ventilation therapy strategies across diverse patient populations by developing an algorithm for accurate identification of patients with acute respiratory failure. To accomplish this objective, our goal was to develop rule-based computable phenotypes for patients with acute respiratory failure using remotely monitored intensive care unit (tele-ICU) data. This approach permits analyses by ventilation strategy across broad patient populations of interest with the ability to sub-phenotype as research questions require. Methods Tele-ICU data from ≥200 hospitals were used to create a rule-based algorithm for phenotyping patients with acute respiratory failure, defined as an adult patient requiring invasive mechanical ventilation or a noninvasive strategy. The dataset spans a wide range of hospitals and ICU types across all US regions. Structured clinical data, including ventilation therapy start and stop times, medication records, and nurse and respiratory therapy charts, were used to define clinical phenotypes. All adult patients of any diagnoses with record of ventilation therapy were included. Patients were categorized by ventilation type, and analysis of event sequences using record timestamps defined each phenotype. Manual validation was performed on 5% of patients in each phenotype. Results We developed 7 phenotypes: (0) invasive mechanical ventilation, (1) noninvasive positive-pressure ventilation, (2) high-flow nasal insufflation, (3) noninvasive positive-pressure ventilation subsequently requiring intubation, (4) high-flow nasal insufflation subsequently requiring intubation, (5) invasive mechanical ventilation with extubation to noninvasive positive-pressure ventilation, and (6) invasive mechanical ventilation with extubation to high-flow nasal insufflation. A total of 27,734 patients met our phenotype criteria and were categorized into these ventilation subgroups. Manual validation of a random selection of 5% of records from each phenotype resulted in a total accuracy of 88% and a precision and recall of 0.8789 and 0.8785, respectively, across all phenotypes. Individual phenotype validation showed that the algorithm categorizes patients particularly well but has challenges with patients that require ≥2 management strategies. Conclusions Our proposed computable phenotyping algorithm for patients with acute respiratory failure effectively identifies patients for therapy-focused research regardless of admission diagnosis or comorbidities and allows for management strategy comparisons across populations of interest.
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Wang, Zihao, Xiaopeng Guo, Wenze Wang, Lu Gao, Xinjie Bao, Ming Feng, Wei Lian, Huijuan Zhu i Bing Xing. "UPLC-MS/MS-based Lipidomic Profiles Revealed Aberrant Lipids Associated with Invasiveness of Silent Corticotroph Adenoma". Journal of Clinical Endocrinology & Metabolism 106, nr 1 (8.08.2020): e273-e287. http://dx.doi.org/10.1210/clinem/dgaa708.
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Abstract Context The accumulation of aberrant lipids and abnormal lipid metabolism in silent corticotroph adenomas (SCAs) could contribute to changes in clinical phenotypes, especially sphenoid sinus invasion. Objective To systematically investigate lipidomic and transcriptomic alterations associated with invasiveness and their potential molecular mechanisms in SCAs and to provide candidate biomarkers for predicting invasiveness and novel treatment options for invasive SCAs by targeting lipids. Methods Fifty-four SCAs (34 invasive/20 noninvasive) were subjected to lipidomic analysis based on ultraperformance liquid chromatography mass spectrometry, and 42 clinically nonfunctioning pituitary adenomas (23 invasive/19 noninvasive) were subjected to transcriptomic analysis. Differential analysis was performed to determine differential lipids and genes between invasive and noninvasive tumors. A functionally connected network was constructed with the molecular pathways as cores. Multiple machine learning methods were applied to identify the most critical lipids, which were further used to construct a lipidomic signature to predict invasive SCAs by multivariate logistic regression, and its performance was evaluated by receiver operating characteristic analysis. Results Twenty-eight differential lipids were identified, and a functionally connected network was constructed with 2 lipids, 17 genes, and 4 molecular pathways. Connectivity Map (CMap) analysis further revealed 32 potential drugs targeting 4 genes and related pathways. The 4 most critical lipids were identified as risk factors contributing to the invasive phenotype. A lipidomic signature was constructed and showed excellent performance in discriminating invasive and noninvasive SCAs. Conclusions The lipidomic signature could serve as a promising predictor for the invasive SCA phenotype and provide potential therapeutic targets for SCAs.
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Kaznatcheev, Artem, Jacob G. Scott i David Basanta. "Edge effects in game-theoretic dynamics of spatially structured tumours". Journal of The Royal Society Interface 12, nr 108 (lipiec 2015): 20150154. http://dx.doi.org/10.1098/rsif.2015.0154.
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Cancer dynamics are an evolutionary game between cellular phenotypes. A typical assumption in this modelling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard for local neighbourhood structure. We address this limitation by using the Ohtsuki–Nowak transform to introduce spatial structure to the go versus grow game. We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary—such as a blood vessel, organ capsule or basement membrane—we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (epithelial–mesenchymal transition-positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Our results caution that pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. Although we concentrate on applications in mathematical oncology, we expect our approach to extend to other evolutionary game models where interaction neighbourhoods change at fixed system boundaries.
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Baxter-Gilbert, James, Julia L. Riley, Carla Wagener, Cláudia Baider, F. B. Vincent Florens, Peter Kowalski, May Campbell i John Measey. "Island Hopping through Urban Filters: Anthropogenic Habitats and Colonized Landscapes Alter Morphological and Performance Traits of an Invasive Amphibian". Animals 12, nr 19 (23.09.2022): 2549. http://dx.doi.org/10.3390/ani12192549.
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A prominent feature of the modern era is the increasing spread of invasive species, particularly within island and urban ecosystems, and these occurrences provide valuable natural experiments by which evolutionary and invasion hypotheses can be tested. In this study, we used the invasion route of guttural toads (Sclerophrys gutturalis) from natural-native and urban-native populations (Durban, South Africa) to their urban-invasive and natural-invasive populations (Mauritius and Réunion) to determine whether phenotypic changes that arose once the toads became urbanized in their native range have increased their invasive potential before they were transported (i.e., prior adaptation) or whether the observed changes are unique to the invasive populations. This urban/natural by native/invasive gradient allowed us to examine differences in guttural toad morphology (i.e., body size, hindlimb, and hindfoot length) and performance capacity (i.e., escape speed, endurance, and climbing ability) along their invasion route. Our findings indicate that invasive island populations have reduced body sizes, shorter limbs in relation to snout-vent length, decreased escape speeds, and decreased endurance capacities that are distinct from the native mainland populations (i.e., invasion-derived change). Thus, these characteristics did not likely arise directly from a pre-transport anthropogenic “filter” (i.e., urban-derived change). Climbing ability, however, did appear to originate within the urban-native range and was maintained within the invasive populations, thereby suggesting it may have been a prior adaptation that provided this species with an advantage during its establishment in urban areas and spread into natural forests. We discuss how this shift in climbing performance may be ecologically related to the success of urban and invasive guttural toad populations, as well as how it may have impacted other island-derived morphological and performance phenotypes.
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Mikheeva, Svetlana A., Nathan D. Camp, Lei Huang, Antrix Jain, Sung Yun Jung, Naze G. Avci, Mari Tokita i in. "TWIST1 Heterodimerization with E12 Requires Coordinated Protein Phosphorylation to Regulate Periostin Expression". Cancers 11, nr 9 (18.09.2019): 1392. http://dx.doi.org/10.3390/cancers11091392.
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Diffuse invasion into adjacent brain matter by glioblastoma (GBM) is largely responsible for their dismal prognosis. Previously, we showed that the TWIST1 (TW) bHLH transcription factor and its regulated gene periostin (POSTN) promote invasive phenotypes of GBM cells. Since TW functional effects are regulated by phosphorylation and dimerization, we investigated how phosphorylation of serine 68 in TW regulates TW dimerization, POSTN expression, and invasion in glioma cells. Compared with wild-type TW, the hypophosphorylation mutant, TW(S68A), impaired TW heterodimerization with the E12 bHLH transcription factor and cell invasion in vitro but had no effect on TW homodimerization. Overexpression of TW:E12 forced dimerization constructs (FDCs) increased glioma cell invasion and upregulated pro-invasive proteins, including POSTN, in concert with cytoskeletal reorganization. By contrast, TW:TW homodimer FDCs inhibited POSTN expression and cell invasion in vitro. Further, phosphorylation of analogous PXSP phosphorylation sites in TW:E12 FDCs (TW S68 and E12 S139) coordinately regulated POSTN and PDGFRa mRNA expression. These results suggested that TW regulates pro-invasive phenotypes in part through coordinated phosphorylation events in TW and E12 that promote heterodimer formation and regulate downstream targets. This new mechanistic understanding provides potential therapeutic strategies to inhibit TW-POSTN signaling in GBM and other cancers.
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Mounger, Jeannie, Malika L. Ainouche, Oliver Bossdorf, Armand Cavé-Radet, Bo Li, Madalin Parepa, Armel Salmon, Ji Yang i Christina L. Richards. "Epigenetics and the success of invasive plants". Philosophical Transactions of the Royal Society B: Biological Sciences 376, nr 1826 (19.04.2021): 20200117. http://dx.doi.org/10.1098/rstb.2020.0117.
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Biological invasions impose ecological and economic problems on a global scale, but also provide extraordinary opportunities for studying contemporary evolution. It is critical to understand the evolutionary processes that underly invasion success in order to successfully manage existing invaders, and to prevent future invasions. As successful invasive species sometimes are suspected to rapidly adjust to their new environments in spite of very low genetic diversity, we are obliged to re-evaluate genomic-level processes that translate into phenotypic diversity. In this paper, we review work that supports the idea that trait variation, within and among invasive populations, can be created through epigenetic or other non-genetic processes, particularly in clonal invaders where somatic changes can persist indefinitely. We consider several processes that have been implicated as adaptive in invasion success, focusing on various forms of ‘genomic shock’ resulting from exposure to environmental stress, hybridization and whole-genome duplication (polyploidy), and leading to various patterns of gene expression re-programming and epigenetic changes that contribute to phenotypic variation or even novelty. These mechanisms can contribute to transgressive phenotypes, including hybrid vigour and novel traits, and may thus help to understand the huge successes of some plant invaders, especially those that are genetically impoverished. This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
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Tot, Tibor, Gyula Pekár, Syster Hofmeyer, Maria Gere, Miklós Tarján, Dan Hellberg i David Lindquist. "Molecular Phenotypes of Unifocal, Multifocal, and Diffuse Invasive Breast Carcinomas". Pathology Research International 2011 (30.11.2011): 1–5. http://dx.doi.org/10.4061/2011/480960.
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We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype.
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Aoki, Tomoko, Naoshi Nishida i Masatoshi Kudo. "Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma". Cancers 14, nr 2 (17.01.2022): 444. http://dx.doi.org/10.3390/cancers14020444.
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Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors has been approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), indicating a critical role of ICIs in the treatment of HCC. However, 20% of patients do not respond effectively to ICIs; mutations in the activation of the Wnt/β-catenin pathway are known to contribute to primary resistance to ICIs. From this point of view, non-invasive detection of Wnt/β-catenin activation should be informative for the management of advanced HCC. Wnt/β-catenin mutations in HCC have a dual aspect, which results in two distinct tumor phenotypes. HCC with minimal vascular invasion, metastasis, and good prognosis is named the “Jekyll phenotype”, while the poorly differentiated HCC subset with frequent vascular invasion and metastasis, cancer stem cell features, and high serum Alpha fetoprotein levels, is named the “Hyde phenotype”. To differentiate these two HCC phenotypes, a combination of the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and fluoro-2-deoxy-D-glucose-PET/CT may be useful. The former is applicable for the detection of the Jekyll phenotype, as nodules present higher enhancement on the hepatobiliary phase, while the latter is likely to be informative for the detection of the Hyde phenotype by showing an increased glucose uptake.
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Duangkham, Samapon, Nicole Welch, Myrian Vega, Sima Shahbandar i James Tarbox. "Approaches to studying the pathogenesis of asthma". Southwest Respiratory and Critical Care Chronicles 10, nr 42 (25.01.2022): 7–11. http://dx.doi.org/10.12746/swrccc.v10i42.987.
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A phenotype describes a group of patients who present with similar clinically observable characteristics. An endotype is a subgroup of patients who share the same pathophysiologic processes that lead to disease presentation. Asthma is a complex chronic disorder that consists of many identifiable phenotypes and two generally accepted endotypes. Understanding the characteristics of the underlying inflammation requires lung biopsies or bronchoalveolar lavage studies, which are invasive and potentially dangerous. There are ongoing investigations that study biomarkers to define asthma phenotypes and endotypes. This article reviews the potential utility of pharmacogenomics, exhaled breath condensates, and serum biomarkers in defining asthma phenotypes and endotypes.
Key words: asthma, pathogenesis, pharmacogenetics, exhaled condensates, biomarkers
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Esipenko, Leonid, Aleksandr Podvarko i Anatoliy Savva. "Phenotypic plasticity of an invasive weed Ambrosia artemisiifolia L. in agrobiocenoses of the South of Russia". BIO Web of Conferences 21 (2020): 00041. http://dx.doi.org/10.1051/bioconf/20202100041.
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Invasive weeds are characterized by high phenotypic plasticity, which allows them to adapt to new climatic conditions due to variable phenotypes that have arisen in the historical time scale under the control of natural selection. Colonization of such plants takes place locally in accessible anthropogenic cenoses. In the South of Russia the most typical invasive plant is Ambrosia artemosiifolia L. We We examined the discrete variation by vegetative feature — shoot length according to 12 genotypes of ragweed in agrocenoses of Krasnodar Krai.
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Williams, Kathryn, Nicola Barnes, Kanwal Cheema, Nikitas Dimopoulos, Miles Howe i Nigel Bundred. "Molecular phenotypes of DCIS predict invasive and DCIS recurrence". European Journal of Surgical Oncology (EJSO) 39, nr 5 (maj 2013): 517. http://dx.doi.org/10.1016/j.ejso.2013.01.015.
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Williams, K. E., N. L. P. Barnes, A. Cramer, R. Johnson, K. Cheema, J. Morris, M. Howe i N. J. Bundred. "Molecular phenotypes of DCIS predict overall and invasive recurrence". Annals of Oncology 26, nr 5 (maj 2015): 1019–25. http://dx.doi.org/10.1093/annonc/mdv062.
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Moellering, Raymond E., Kvar C. Black, Chetan Krishnamurty, Brenda K. Baggett, Phillip Stafford, Matthew Rain, Robert A. Gatenby i Robert J. Gillies. "Acid treatment of melanoma cells selects for invasive phenotypes". Clinical & Experimental Metastasis 25, nr 4 (27.02.2008): 411–25. http://dx.doi.org/10.1007/s10585-008-9145-7.
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Franssen, Linnea C., i Mark A. J. Chaplain. "A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer". IMA Journal of Applied Mathematics 85, nr 5 (10.09.2020): 724–61. http://dx.doi.org/10.1093/imamat/hxaa022.
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Abstract Cancer invasion and metastatic spread to secondary sites in the body are facilitated by a complex interplay between cancer cells of different phenotypes and their microenvironment. A trade-off between the cancer cells’ ability to invade the tissue and to metastasize, and their ability to proliferate has been observed. This gives rise to the classification of cancer cells into those of mesenchymal and epithelial phenotype, respectively. Additionally, mixed phenotypic states between these two extremes exist. Cancer cells can transit between these states via epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). These processes are crucial for both the local tissue invasion and the metastatic spread of cancer cells. To shed light on the role of these phenotypic states and the transitions between them in the invasive and metastatic process, we extend our recently published multi-grid, hybrid, individual-based mathematical metastasis framework (Franssen et al. 2019, A mathematical framework for modelling the metastatic spread of cancer. Bull. Math. Biol., 81, 1965). In addition to cancer cells of epithelial and of mesenchymal phenotype, we now also include those of an intermediate partial-EMT phenotype. Furthermore, we allow for the switching between these phenotypic states via EMT and MET at the biologically appropriate steps of the invasion-metastasis cascade. We also account for the likelihood of spread of cancer cells to the various secondary sites and differentiate between the tissues of the organs involved in our simulations. Finally, we consider the maladaptation of metastasized cancer cells to the new tumour microenvironment at secondary sites as well as the immune response at these sites by accounting for cancer cell dormancy and death. This way, we create a first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade.
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Liu, Yan, Corinne Ramos, Pierre Baudot, Johan Brag i Olivier Lucidarme. "Imaging biomarker phenotyping system (iBiopsy) to accelerate hepatocellular carcinoma (HCC) drug development." Journal of Clinical Oncology 37, nr 15_suppl (20.05.2019): e15671-e15671. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15671.
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e15671 Background: Current drug therapies in HCC remain limited because of substantial genomic, cellular and molecular heterogeneity of the liver tumor microenvironment (TME). This heterogeneity has implications for tumor development, immune response and cellular invasion and is compounded by multiple molecular pathways related to the various HCC etiologies. In this context, it is challenging to find biomarkers that are predictive of therapeutic response or outcome. A systems biology approach leveraging the iBiopsy phenotyping platform to automatically detect HCC and TME subtypes using non-invasive medical imaging could help identify specific disease pathways and accelerate HCC drug development. Methods: In this retrospective study, 50 patients with primary HCC were used to extract voxel level image signatures from the segmented livers on CT scans. The automatic classification of liver signatures was obtained by Log Linear Local density peak clustering computed using Wasserstein’s optimal transport distance between Gray Level Co-occurrence matrices of local luminance tiles of the Liver. Through this hypothesis-free clustering, phenotypes representative of tumor and tumor environment were identified and further correlated with clinical data. Results: Nine classes of statistically significantly distant clusters were identified on the 50 patients. Preliminary correlation analysis on individual patient showed that up to 3 clusters were specific to the tumor and characterized phenotype heterogeneity within the tumor. Notably, specific clusters at the tumor front-line and surrounding adjacent non-tumoral tissue were also identified. Conclusions: Preliminary results show that a multiplicity of phenotypes representative of a complex heterogeneous lesion and tissue microenvironment that might have prognostic and predictive value can be identified. This support the use of a non-invasive phenotypic approach for the subtyping of HCC that can be used for the identification of a multiplicity of important biological pathways that can be specifically targeted to treat HCC.
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VINCENT, THOMAS L., i ROBERT A. GATENBY. "MODELING CANCER AS AN EVOLUTIONARY GAME". International Game Theory Review 07, nr 03 (wrzesień 2005): 331–46. http://dx.doi.org/10.1142/s0219198905000557.
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We present two different mathematical models that examine the role of cellular evolution in the development and treatment of cancer. The first is a Lotka-Volterra model of an invasive cancer subjected to chemotherapy that demonstrates rapid evolution of drug-resistant phenotypes. The second model represents a major refinement of the first one with the objective of producing a simple, but realistic model of carcinogenesis. It is a consumer-resource model (consumers = normal + mutuant cells, resource = glucose). We conclude that if mutant cells are not allowed to evolve, they will not ordinarily progress to cancer. However, if accumulating mutations allow cellular evolution and successful adaptation to proliferation constraints, normal cells will develop into invasive cancer. We find this progression is possible because normal cellular populations are not at an evolutionarily stable state and so are subject to invasion by more fit phenotypes.
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Wu, Tony James. "Identifying mechanisms of macrophage-induced metastasis in pancreatic ductal adenocarcinoma." Journal of Clinical Oncology 37, nr 15_suppl (20.05.2019): e15705-e15705. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15705.
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e15705 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal, incurable disease. Macrophages are one of the most abundant, multifunctional immune cell populations in the tumor microenvironment and a major component of the immune infiltrate in many solid tumors. Methods: Employing a multi-omics approach, PDAC cell lines and primary macrophages were CTAP (cell-type specific labelling using amino acid precursors)-labelled and admixed together for a prolonged period of time. To identify cell-of-origin of novel RNA and proteins, these mixed co-cultures were FACS sorted for downstream RNA-sequencing analysis or harvested in bulk for downstream proteome and secretome analysis. Results: Here, we provide new insight into the dichotomous relationship between epithelial and mesenchymal phenotypes of PDAC cells in 3D culture. We report the ability of PDAC mesenchymal cells to form vascular mimicry-like structures in a 3D in vitro assay of invasion. Additionally, we demonstrate that macrophages have the ability to impart a pro-invasive phenotype to PDAC cells when co-cultured in 3D, regardless of EMT (epithelial-to-mesenchymal transition) status. Preliminary integration of cell culture transcriptomes with CTAP-TMT proteomes and secretomes implicates several key epithelial- and macrophage-derived signalling molecules as principal instructing signals for mediating the observed pro-invasive phenotype. Conclusions: Blockade of these signalling molecules or their receptors disrupted the crosstalk between PDAC cells and macrophages within the tumor microenvironment and impaired the ability of macrophages to induce a pro-invasive phenotype to PDAC cells.
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Hong, Keun-Seok, Hyemin Kim, Seon-Hee Kim, Minju Kim i Jiyun Yoo. "Calponin 3 Regulates Cell Invasion and Doxorubicin Resistance in Gastric Cancer". Gastroenterology Research and Practice 2019 (18.02.2019): 1–7. http://dx.doi.org/10.1155/2019/3024970.
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Calponin 3 (CNN3) is an F-actin-binding protein that regulates actin cytoskeletal rearrangement. However, the role of CNN3 in cancer cell invasion and resistance to chemotherapeutic agents has not yet been investigated. The present study was undertaken to investigate whether CNN3 influences cancer-related phenotypes in gastric cancer. We demonstrate that CNN3 contributes to cell invasion and resistance to doxorubicin in gastric cancer. CNN3 expression was markedly elevated in highly invasive cancer cell lines compared to less invasive or noninvasive cancer cell lines. Depletion of CNN3 protein suppressed the invasive ability of gastric cancer cells. The highly invasive MKN-28 gastric cancer cells were more resistant to doxorubicin than the noninvasive MKN-45 cells; however, knockdown of CNN3 expression in MKN-28 cells resensitized them to doxorubicin treatment. Taken together, our results suggest that CNN3 plays a key role in invasiveness and doxorubicin resistance in gastric cancer cells.
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Gao, ChongFeng, Yanli Su, Julie Koeman, Elizabeth Haak, Karl Dykema, Curt Essenberg, Eric Hudson, David Petillo, Sok Kean Khoo i George F. Vande Woude. "Chromosome instability drives phenotypic switching to metastasis". Proceedings of the National Academy of Sciences 113, nr 51 (5.12.2016): 14793–98. http://dx.doi.org/10.1073/pnas.1618215113.
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Chromosome instability (CIN) is the most striking feature of human cancers. However, how CIN drives tumor progression to metastasis remains elusive. Here we studied the role of chromosome content changes in generating the phenotypic dynamics that are required for metastasis. We isolated epithelial and mesenchymal clones from human carcinoma cell lines and showed that the epithelial clones were able to generate mesenchymal variants, which had the potential to further produce epithelial revertants autonomously. The successive acquisition of invasive mesenchymal and then epithelial phenotypes recapitulated the steps in tumor progression to metastasis. Importantly, the generation of mesenchymal variants from clonal epithelial populations was associated with subtle changes in chromosome content, which altered the chromosome transcriptome and influenced the expression of genes encoding intercellular junction (IJ) proteins, whereas the loss of chromosome 10p, which harbors the ZEB1 gene, was frequently detected in epithelial variants generated from mesenchymal clones. Knocking down these IJ genes in epithelial cells induced a mesenchymal phenotype, whereas knocking down the ZEB1 gene in mesenchymal cells induced an epithelial phenotype, demonstrating a causal role of chromosome content changes in phenotypic determination. Thus, our studies suggest a paradigm of tumor metastasis: primary epithelial carcinoma cells that lose chromosomes harboring IJ genes acquire an invasive mesenchymal phenotype, and subsequent chromosome content changes such as loss of 10p in disseminated mesenchymal cells generate epithelial variants, which can be selected for to generate epithelial tumors during metastatic colonization.
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Matsumoto, Yuji, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Yoshihiro Otani, Atsushi Fujimura, Kentaro Fujii, Yosuke Shimazu i in. "ANGI-08. AN ANNEXIN A2-REGULATED PHENOTYPIC SHIFT IN GLIOMA". Neuro-Oncology 21, Supplement_6 (listopad 2019): vi31—vi32. http://dx.doi.org/10.1093/neuonc/noz175.119.
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Abstract BACKGROUND Malignant glioma has a poor prognosis and is characterized by excessive proliferation, invasion, and angiogenesis. Previously, we established subclones of glioma cell lines with different invasive phenotypes to investigate the mechanisms of invasion in this malignancy. That study revealed annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we investigated the molecular mechanism of the phenotypic shift in glioma that is induced by ANXA2. METHODS We identified ANXA2 target genes using microarray analyses of our four established cell lines and RNA-seq data from the IVY Glioblastoma Atlas Project. Co-expression was then confirmed in human glioma cells. Additionally, qRT-PCR, immunoblotting, invasion assays, proliferation assays, and tube formation assays were performed to uncover the specific roles of these angiogenic invasion-related genes. Furthermore, we examined survival times and phenotypic shifts in vivo. RESULTS We identified oncostatin M receptor (OSMR) as an ANXA2-target gene using microarray and RNA-seq, and confirmed its expression correlated with ANXA2 in glioma cells. ANXA2-overexpressing glioma cells showed enhanced OSMR expression and STAT3 phosphorylation, while STAT3 knockdown reduced OSMR expression. When ANXA2 was overexpressed in glioma cells, invasion, angiogenesis, proliferation, and epithelial-mesenchymal transition were promoted; however, silencing OSMR attenuated the ANXA2-induced phenotypic shift. In vivo, ANXA2-overexpressing glioma cells shortened the survival time of tumor-bearing mice, whereas OSMR knockdown increased survival times. CONCLUSIONS We analyzed genes whose expression was regulated by ANXA2 in glioma using invasive glioma models. Through this analysis, we identified that ANXA2 and OSMR regulate a phenotypic shift, suggesting that OSMR could be a promising target to treat and prevent glioma invasion.
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de Castro-Miró, Marta, Raul Tonda, Gemma Marfany, Ricardo P. Casaroli-Marano i Roser Gonzàlez-Duarte. "Novel mutation in the choroideremia gene and multi-Mendelian phenotypes in Spanish families". British Journal of Ophthalmology 102, nr 10 (24.01.2018): 1378–86. http://dx.doi.org/10.1136/bjophthalmol-2017-311427.
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AimsWe aimed to accurately diagnose several retinitis pigmentosa (RP) patients with complex ocular phenotypes by combining massive sequencing genetic diagnosis and powerful clinical imaging techniques.MethodsWhole-exome sequencing (WES) of selected patients from two RP families was undertaken. The variants identified were validated by Sanger sequencing and cosegregation analysis. Accurate clinical re-evaluation was performed using electrophysiological and visual field records as well as non-invasive imaging techniques, such as swept-source optical coherence tomography and fundus autofluorescence.ResultsThe WES results highlighted one novel and one reported causative mutations in the X-linked choroideremia gene (CHM), which challenged the initial RP diagnosis. Subsequent clinical re-evaluation confirmed the choroideremia diagnosis. Carrier females showed different degrees of affectation, even between twin sisters, probably due to lyonization. A severe multi-Mendelian phenotype was associated with coincidental dominant pathogenic mutations in two additional genes: PAX6 and PDE6B.ConclusionsGenetic diagnosis via massive sequencing is instrumental in identifying causative mutations in retinal dystrophies and additional genetic variants with an impact on the phenotype. Multi-Mendelian phenotypes previously ascribed to rare syndromes can thus be dissected and molecularly diagnosed. Overall, the combination of powerful genetic diagnosis and clinical non-invasive imaging techniques enables efficient management of patients and their prioritisation for gene-specific therapies.
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Basu, Moitri, Isha Sengupta, Md Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy i Chandrima Das. "Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes". Biochemical Journal 474, nr 11 (19.05.2017): 1919–34. http://dx.doi.org/10.1042/bcj20170223.
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Enhanced migratory potential and invasiveness of cancer cells contribute crucially to cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed a chromatin reader. ZMYND8 [zinc finger MYND (myeloid, Nervy and DEAF-1)-type containing 8], a key component of the transcription regulatory network, has recently been shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8. Detailed analysis uncovered its antiproliferative activity through BrdU incorporation, alteration in the expression of proliferation markers, and cell cycle regulating genes and cell viability assays. In addition, performing wound healing and invasion/migration assays, its anti-invasive nature is evident. Interestingly, epithelial–mesenchymal transition (EMT), a key mechanism of cellular invasion, is regulated by ZMYND8 where we identified its selective enrichment on promoters of CLDN1/CDH1 genes, rich in H3K36Me2/H4K16Ac marks, leading to their up-regulation. Thus, the presence of ZMYND8 could be implicated in maintaining the epithelial phenotype of cells. Furthermore, syngeneic mice, injected with ZMYND8-overexpressed invasive breast cancer cells, showed reduction in tumor volume and weight. In concert with this, we observed a significant down-regulation of ZMYND8 in invasive ductal and lobular breast cancer tissues compared with normal tissue. Taken together, our study elucidates a novel function of ZMYND8 in regulating EMT and invasion of cancer cells, possibly through its chromatin reader function.
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Naumann, Max, Natalie Arend, Rustam R. Guliev, Christian Kretzer, Ignacio Rubio, Oliver Werz i Ute Neugebauer. "Label-Free Characterization of Macrophage Polarization Using Raman Spectroscopy". International Journal of Molecular Sciences 24, nr 1 (3.01.2023): 824. http://dx.doi.org/10.3390/ijms24010824.
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Macrophages are important cells of the innate immune system that play many different roles in host defense, a fact that is reflected by their polarization into many distinct subtypes. Depending on their function and phenotype, macrophages can be grossly classified into classically activated macrophages (pro-inflammatory M1 cells), alternatively activated macrophages (anti-inflammatory M2 cells), and non-activated cells (resting M0 cells). A fast, label-free and non-destructive characterization of macrophage phenotypes could be of importance for studying the contribution of the various subtypes to numerous pathologies. In this work, single cell Raman spectroscopic imaging was applied to visualize the characteristic phenotype as well as to discriminate between different human macrophage phenotypes without any label and in a non-destructive manner. Macrophages were derived by differentiation of peripheral blood monocytes of human healthy donors and differently treated to yield M0, M1 and M2 phenotypes, as confirmed by marker analysis using flow cytometry and fluorescence imaging. Raman images of chemically fixed cells of those three macrophage phenotypes were processed using chemometric methods of unmixing (N-FINDR) and discrimination (PCA-LDA). The discrimination models were validated using leave-one donor-out cross-validation. The results show that Raman imaging is able to discriminate between pro- and anti-inflammatory macrophage phenotypes with high accuracy in a non-invasive, non-destructive and label-free manner. The spectral differences observed can be explained by the biochemical characteristics of the different phenotypes.
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Rasmussen, Neal R., Zufan Debebe, Tricia M. Wright, Samira A. Brooks, Adam B. Sendor, A. Rose Brannon, A. Ari Hakimi i in. "Expression of Ror2 Mediates Invasive Phenotypes in Renal Cell Carcinoma". PLoS ONE 9, nr 12 (26.12.2014): e116101. http://dx.doi.org/10.1371/journal.pone.0116101.
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Burandt, Eike, Niclas C. Blessin, Ann-Christin Rolschewski, Florian Lutz, Tim Mandelkow, Cheng Yang, Elena Bady i in. "T-Cell Density at the Invasive Margin and Immune Phenotypes Predict Outcome in Vulvar Squamous Cell Cancer". Cancers 14, nr 17 (31.08.2022): 4246. http://dx.doi.org/10.3390/cancers14174246.
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Background: Although quantification of tumor infiltrating lymphocytes (TILs) has become of increasing interest in immuno-oncology, only little is known about TILs infiltration in the tumor microenvironment and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3+ (DAKO, #IR503) and CD8+ (DAKO, #IR623) TILs at the invasive margin and in the center of 530 vulvar squamous cell cancers. Results: An elevated density of CD3+ T-cell at the invasive margin was significantly associated with low tumor stage (p = 0.0012) and prolonged survival (overall survival [OS] p = 0.0027, progression free survival [PFS] p = 0.024) and was independent from tumor stage, nodal stage, grade, and HPV-status in multivariate analysis (p < 0.05). The prognostic impact of CD3+ cells in the center of the tumor was weaker compared to the invasive margin (OS p = 0.046, PFS p = 0.031) and lacking for CD8+ T-cell densities at any location (p ≥ 0.14 each). Unsupervised clustering of CD3+ and CD8+ T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (p = 0.0071) and PFS (p = 0.0027). Conclusion: Our data demonstrate a high prognostic value of CD3+ T-cells at the invasive margin and immune phenotypes in vulvar squamous cell cancer.
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Both, Anna, Jiabin Huang, Minyue Qi, Christian Lausmann, Samira Weißelberg, Henning Büttner, Susanne Lezius i in. "Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations". PLOS Pathogens 17, nr 2 (5.02.2021): e1009304. http://dx.doi.org/10.1371/journal.ppat.1009304.
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S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.
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Desprez, Pierre-Yves, Claudia Qiao Lin, Nicole Thomasset, Carolyn J. Sympson, Mina J. Bissell i Judith Campisi. "A Novel Pathway for Mammary Epithelial Cell Invasion Induced by the Helix-Loop-Helix Protein Id-1". Molecular and Cellular Biology 18, nr 8 (1.08.1998): 4577–88. http://dx.doi.org/10.1128/mcb.18.8.4577.
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ABSTRACT Mammary epithelial cells undergo changes in growth, invasion, and differentiation throughout much of adulthood, and most strikingly during pregnancy, lactation, and involution. Although the pathways of milk protein expression are being elucidated, little is known, at a molecular level, about control of mammary epithelial cell phenotypes during normal tissue morphogenesis and evolution of aggressive breast cancer. We developed a murine mammary epithelial cell line, SCp2, that arrests growth and functionally differentiates in response to a basement membrane and lactogenic hormones. In these cells, expression of Id-1, an inhibitor of basic helix-loop-helix transcription factors, declines prior to differentiation, and constitutive Id-1 expression blocks differentiation. Here, we show that SCp2 cells that constitutively express Id-1 slowly invade the basement membrane but remain anchorage dependent for growth and do not form tumors in nude mice. Cells expressing Id-1 secreted a ∼120-kDa gelatinase. From inhibitor studies, this gelatinase appeared to be a metalloproteinase, and it was the only metalloproteinase detectable in conditioned medium from these cells. A nontoxic inhibitor diminished the activity of this metalloproteinase in vitro and repressed the invasive phenotype of Id-1-expressing cells in culture. The implications of these findings for normal mammary-gland development and human breast cancer were investigated. A gelatinase of ∼120 kDa was expressed by the mammary gland during involution, a time when Id-1 expression is high and there is extensive tissue remodeling. Moreover, high levels of Id-1 expression and the activity of a ∼120-kDa gelatinase correlated with a less-differentiated and more-aggressive phenotype in human breast cancer cells. We suggest that Id-1 controls invasion by normal and neoplastic mammary epithelial cells, primarily through induction of a ∼120-kDa gelatinase. This Id-1-regulated invasive phenotype could contribute to involution of the mammary gland and possibly to the development of invasive breast cancer.
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Aleksandrov, M. V., i Y. V. Marchenko. "Neurophysiological phenotypes of pharmacoresistant temporal lobe epilepsy". Medical alphabet, nr 15 (6.07.2021): 9–12. http://dx.doi.org/10.33667/2078-5631-2021-15-9-12.
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Patients with a drug-resistant form of epilepsy can be treated by neurosurgery through the destruction or separation of the epileptic focus. If the results of clinical, neuro-imaging and neurophysiological methods are discordant, then the localization of the epileptogenic zone is performed based on the results of long-term invasive monitoring of the bioelectrical activity of the cortex and deep structures of the brain. The aim of this work was the retrospective analysis of the results of invasive monitoring of the bioelectrical activity of the brain to clarify the mechanisms of the formation of patterns of interictal and ictal activity in structural epilepsy. The study included 35 patients (18 men, 17 women) with drug-resistant temporal lobe epilepsy, who were treated at the Polenov Neurosurgical Institute. The examination included video-EEG monitoring, long-term invasive monitoring of bioelectrical activity of the cortex, and deep brain structures. The patients were divided into two groups according to the type of surgical treatment: 1) micro-surgical resection of the epileptic focus, including the zone of structural changes (24 patients); 2) stereotactic destruction of the amygdala-hippocampal complex (6 patients). The follow-up of the outcomes of the surgical treatment took place over 2-3 years. Depending on the results of the surgical treatment, the patients were divided into two groups: 1) patients with a favorable outcome (Engel 1–2) — 15 patients and 2) patients with no positive dynamics and a relatively poor outcome (Engel 3–4) — 15 patients. The results obtained showed that the patterns of interictal and ictal activity in their totality determine the neurophysiology, i.e the phenotype of temporal lobe epilepsy, reflecting the interference of pathogenetic and sanogenetic mechanisms. The localization of the epileptogenic zone should be based on the cumulative assessment of interictal and ictal activity. The presence of more than one focus of interictal activity, the secondary spread of epileptiform activity from the primary focus, are prognostically unfavorable factors.
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Evans, David J., Dara W. Frank, Viviane Finck-Barbançon, Christine Wu i Suzanne M. J. Fleiszig. "Pseudomonas aeruginosa Invasion and Cytotoxicity Are Independent Events, Both of Which Involve Protein Tyrosine Kinase Activity". Infection and Immunity 66, nr 4 (1.04.1998): 1453–59. http://dx.doi.org/10.1128/iai.66.4.1453-1459.1998.
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ABSTRACT Pseudomonas aeruginosa clinical isolates exhibit invasive or cytotoxic phenotypes. Cytotoxic strains acquire some of the characteristics of invasive strains when a regulatory gene,exsA, that controls the expression of several extracellular proteins, is inactivated. exsA mutants are not cytotoxic and can be detected within epithelial cells by gentamicin survival assays. The purpose of this study was to determine whether epithelial cell invasion precedes and/or is essential for cytotoxicity. This was tested by measuring invasion (gentamicin survival) and cytotoxicity (trypan blue staining) of PA103 mutants deficient in specificexsA-regulated proteins and by testing the effect of drugs that inhibit invasion for their effect on cytotoxicity. A transposon mutant in the exsA-regulated extracellular factorexoU was neither cytotoxic nor invasive. Furthermore, several of the drugs that inhibited invasion did not prevent cytotoxicity. These results show that invasion and cytotoxicity are mutually exclusive events, inversely regulated by anexsA-encoded invasion inhibitor(s). Both involve host cell protein tyrosine kinase (PTK) activity, but they differ in that invasion requires Src family tyrosine kinases and calcium-calmodulin activity. PTK inhibitor drugs such as genistein may have therapeutic potential through their ability to block both invasive and cytotoxicity pathways via an action on the host cell.
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Mukhopadhyay, Utpal K., Robert Eves, Lilly Jia, Patrick Mooney i Alan S. Mak. "p53 Suppresses Src-Induced Podosome and Rosette Formation and Cellular Invasiveness through the Upregulation of Caldesmon". Molecular and Cellular Biology 29, nr 11 (6.04.2009): 3088–98. http://dx.doi.org/10.1128/mcb.01816-08.
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ABSTRACT The tumor-suppressive role of p53 at the level of tumor initiation is well documented. It has also been shown previously that p53 acts against tumor progression/metastasis. However, its role in modulating cell migration and invasion leading to metastasis is poorly understood. In this study, using vascular smooth muscle cells and NIH 3T3 fibroblast cells, we have shown that p53 potently suppresses Src-induced podosome/rosette formation, extracellular matrix digestion, cell migration, and invasion. The overexpression of exogenous wild-type p53 or the activation of the endogenous p53 function suppresses, while the short hairpin RNA-mediated knockdown of p53 expression or the blocking of its function exacerbates, Src-induced migratory and invasive phenotypes. We have also found that p53 expression and function are downregulated in cells stably transformed with constitutively active Src that exhibit aggressive invasive properties. Lastly, p53 upregulates the expression of caldesmon, an actin-binding protein that has been shown to be an inhibitor of podosome/invadopodium formation. The ability of p53 to suppress Src phenotypes in transformed cells was largely abolished by knocking down caldesmon. This study reports a novel molecular mechanism (caldesmon), as well as a structural basis (podosomes/rosettes), to show how p53 can act as an anti-motility/invasion/metastasis agent.
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Kuo, Chi-Yu, Yuan-Ching Chang, Ming-Nan Chien, Jie-Yang Jhuang, Yi-Chiung Hsu, Shih-Yuan Huang i Shih-Ping Cheng. "SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway". Endocrine-Related Cancer 29, nr 2 (1.02.2022): 47–58. http://dx.doi.org/10.1530/erc-21-0256.
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Aberrant lipid metabolism provides bioenergetic, biosynthetic, and redox supplies to cancer cells. Previous studies have reported differential lipid profiling in thyroid malignancies. Sterol regulatory element-binding protein 1 (SREBP1), encoded by the SREBF1 gene, is a master regulator of cellular lipid homeostasis. The clinical and functional significance of SREBP1 in thyroid cancer is not well understood. Here, we showed that SREBP1 expression is significantly upregulated in invasive thyroid cancer than in normal thyroid tissue or benign thyroid nodules. High tumoral SREBP1 expression was associated with extrathyroidal extension, advanced disease stage, and shorter disease-specific survival in patients with differentiated thyroid cancer. SREBP1 overexpression significantly increased the oxygen consumption rate, filopodia formation, and migratory and invasive capacities of thyroid cancer cells. Knockdown of SREBF1 or treatment with an SREBP1 activation inhibitor fatostatin had the opposite effect. RNA-Seq analysis showed that modulation of SREBP1 expression was accompanied by corresponding changes in the expression of epithelial–mesenchymal transition markers and CYR61/CTGF. SREBP1-facilitated cell invasion could be abrogated by treatment with a YAP inhibitor such as verteporfin or genetic silencing of CYR61 or CTGF. In summary, SREBP1 upregulation can be used as a prognostic indicator for thyroid cancer and SREBP1 overexpression is involved in cancer invasiveness, at least partly, through upregulation of CYR61/CTGF via the Hippo-YAP pathway.
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Fritah, Asmaà, Cécile Saucier, Olivier De Wever, Marc Bracke, Ivan Bièche, Rosette Lidereau, Christian Gespach, Sylvain Drouot, Gérard Redeuilh i Michèle Sabbah. "Role of WISP-2/CCN5 in the Maintenance of a Differentiated and Noninvasive Phenotype in Human Breast Cancer Cells". Molecular and Cellular Biology 28, nr 3 (18.12.2007): 1114–23. http://dx.doi.org/10.1128/mcb.01335-07.
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ABSTRACT WISP-2/CCN5 is an estrogen-regulated member of the “connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed” (CCN) family of the cell growth and differentiation regulators. The WISP-2/CCN5 mRNA transcript is undetectable in normal human mammary cells, as well as in highly aggressive breast cancer cell lines, in contrast with its higher level in the breast cancer cell lines characterized by a more differentiated phenotype. We report here that knockdown of WISP-2/CCN5 by RNA interference in estrogen receptor alpha (ERα)-positive MCF-7 breast cancer cells induced an estradiol-independent growth linked to a loss of ERα expression and promoted epithelial-to-mesenchymal transdifferentiation. In contrast, forced expression of WISP-2/CCN5 directed MCF-7 cells toward a more differentiated phenotype. When introduced into the poorly differentiated, estrogen-independent, and invasive MDA-MB-231 breast cancer cells, WISP-2/CCN5 was able to reduce their proliferative and invasive phenotypes. In a series of ERα-positive tumor biopsies, we found a positive correlation between the expression of WISP-2/CCN5 and ID2, a transcriptional regulator of differentiation in normal and transformed breast cells. We propose that WISP-2/CCN5 is an important regulator involved in the maintenance of a differentiated phenotype in breast tumor epithelial cells and may play a role in tumor cell invasion and metastasis.
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Prudhomme, Jorian, Enkelejda Velo, Silvia Bino, Perparim Kadriaj, Kujtim Mersini, Filiz Gunay i Bulent Alten. "Altitudinal variations in wing morphology of Aedes albopictus (Diptera, Culicidae) in Albania, the region where it was first recorded in Europe". Parasite 26 (2019): 55. http://dx.doi.org/10.1051/parasite/2019053.
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The rapid spread and settlement of Aedes albopictus mosquitoes across at least 28 countries in Europe, as well as several countries in Asia Minor, the Middle East and Africa, has made it one of the most invasive species of all time. Even though the biology of Ae. albopictus in its native tropical environment has been documented for a long time, the biology and ecology of this species in newly colonized temperate environments remain poorly known despite its important role as a vector for about twenty arboviruses. In this context, the main goals of this work were to investigate Ae. albopictus phenotypic variations at a local scale in Albania, the country where Ae. albopictus was first recorded in Europe, and to determine if its phenotypes could be affected by altitude. Analysis of Ae. albopictus wing phenotypes was performed using a geometric morphometric approach. We observed shape and size variations among altitudinal populations of Ae. albopictus. Differences of wing phenotypes were highlighted between altitude groups for male and female mosquitoes. The phenotypic variations observed in Ae. albopictus between altitudinal groups indicated these populations are exposed to environmental and ecological pressures. These results suggest the presence of phenotypic plasticity in this species.
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Zukowski, Alexis, Satyanarayan Rao i Srinivas Ramachandran. "Phenotypes from cell-free DNA". Open Biology 10, nr 9 (wrzesień 2020): 200119. http://dx.doi.org/10.1098/rsob.200119.
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Cell-free DNA (cfDNA) has the potential to enable non-invasive detection of disease states and progression. Beyond its sequence, cfDNA also represents the nucleosomal landscape of cell(s)-of-origin and captures the dynamics of the epigenome. In this review, we highlight the emergence of cfDNA epigenomic methods that assess disease beyond the scope of mutant tumour genotyping. Detection of tumour mutations is the gold standard for sequencing methods in clinical oncology. However, limitations inherent to mutation targeting in cfDNA, and the possibilities of uncovering molecular mechanisms underlying disease, have made epigenomics of cfDNA an exciting alternative. We discuss the epigenomic information revealed by cfDNA, and how epigenomic methods exploit cfDNA to detect and characterize cancer. Future applications of cfDNA epigenomic methods to act complementarily and orthogonally to current clinical practices has the potential to transform cancer management and improve cancer patient outcomes.