| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 2. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 3. |
- Yan, Bao-Yong, et al.
(författare)
-
Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation
- 2010
-
Ingår i: Chemotherapy. - : S, Karger AG, Basel. - 0009-3157 .- 1421-9794. ; 56:6, s. 424-428
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.
|
|
| 4. |
- Zhang, Yinping, et al.
(författare)
-
Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China
- 2013
-
Ingår i: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4182-4189
-
Tidskriftsartikel (refereegranskat)abstract
- Asthma, rhinitis and eczema (allergic or non-allergic) have increased throughout the world during the last decades, especially among children. Changes in the indoor environment are suspected to be important causes. China has experienced a dramatic change in indoor environmental exposures during the past two decades. However, such changes and their associations with children's asthma and other health aspects have not been thoroughly studied. China, Children, Homes, Health (CCHH), Phase I, was a cross-sectional questionnaire survey of 48219 children 1-8 years old in 10 Chinese cities during 2010-2012. The questionnaire includes the International Study of Asthma and Allergies in Childhood (ISAAC) core health questions and additional questions regarding housing, life habits and outdoor environment. In health analyses, children aged 3-6 years old were included. The prevalences of doctor diagnosed asthma varied from 1.7% to 9.8% (mean 6.8%), a large increase from 0.91% in 1999 and 1.50% in 2000. The prevalence of wheeze, rhinitis and atopic eczema (last 12 months) varied from 13.9% to 23.7%, 24.0% to 50.8% and 4.8% to 15.8%, respectively. Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest, except for wheezewhere the highest value was for Urumqi. We found (1) no obvious association between disease prevalences and ambient PM10 concentrations and (2) higher prevalences of disease in humid climates with hot summers and cold winters, but with no centrally heated buildings. Associations between the diseases and economic status as indexed by Gross Domestic Product (GDP) requires further study.
|
|
| 5. |
- Cho, Yoon Shin, et al.
(författare)
-
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
-
Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
|
|
| 6. |
- Wei, Yi-Ming, et al.
(författare)
-
Responsibility accounting in carbon allocation : A global perspective
- 2014
-
Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 130, s. 122-133
-
Tidskriftsartikel (refereegranskat)abstract
- Regarding the carbon emissions allocation principles, whether historical responsibility can be and how to be incorporated into the global climate framework is still under heated discussions. Here we argue that the permits share of most developed countries will sharply shrink when historical responsibilities are taken in through our assessment and comparison of six selected allocation proposals. To find a more convincing way of responsibility shift, we modify the existing method by giving each participant an independent year, decided by comparing its economic development with reference to China, as the start point to calculate its own responsibilities quantified by the historical cumulative emissions. Then we obtain carbon emission accounts of 137 countries and regions on the basis of per-capita cumulative emissions. Compared with the conventional method, there is an average 2.5% increase in emission deficits of the U.S.A, Canada and Japan, however, a 50% decline in emission deficits of OECD Europe; emission revenues of China, India and Brazil decrease by 39%. This paper presents a systematic and quantitative method to achieve a common but differentiated responsibility shift, not only between developed and developing countries but also within industrialized countries, in the hope of providing the framework for rational allocation of carbon emissions to be deliberated in the forthcoming climate change program of the United Nations.
|
|
| 7. |
- Zhao, Zeng-Ren, et al.
(författare)
-
Increased serum level of Nup88 protein is associated with the development of colorectal cancer
- 2012
-
Ingår i: Medical Oncology. - : Humana Press (Springer Imprint). - 1357-0560 .- 1559-131X. ; 29:3, s. 1789-1795
-
Tidskriftsartikel (refereegranskat)abstract
- Nucleoporin88 (Nup88) has been shown to be overexpressed in a wide variety of malignancies including colorectal cancer (CRC). However, no study about serum Nup88 in human CRC was reported. Therefore, in this study, we investigated the level of serum Nup88 protein and its relationships with clinicopathological variables in CRC. The serum concentration of Nup88 protein was determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) in 118 pre-operative serum samples, 66 post-operative and 96 healthy controls. Among the patients, the levels of CEA (n = 91) and CA19-9 (n = 87) in the pre-operative serum were measured, and DNA sequencing was performed in 12 CRCs and 2 samples from non-cancerous colon tissue. In the same patients, the level of pre-operative serum Nup88 was significantly higher than that of post-operative Nup88 (P = 0.021). Furthermore, the level of pre-operative Nup88 was positively related to the depth of tumor invasion (P = 0.002) and advanced stage (P = 0.001). The level of pre-operative Nup88 in the left colon tended to be higher than that in the right colon and the rectum (P = 0.063). DNA sequencing results showed that there were two single nucleotide polymorphisms, distributed in exon 6 (NM_002532.3:c.1044Gandgt;A (ACG-ACA, Thr -andgt; Thr) and exon 10 (NM_002532.3: c.1389Aandgt;T, CCA-CCT, Pro -andgt; Pro). Serum Nup88 might be a candidate for a new biomarker implicated in the development and aggressiveness of CRCs.
|
|
| 8. |
- Zhao, Zeng-Ren, et al.
(författare)
-
Significance of mRNA and Protein Expression of MAC30 in Progression of Colorectal Cancer
- 2011
-
Ingår i: Chemotherapy. - Basel : Karger AG. - 0009-3157 .- 1421-9794. ; 57:5, s. 394-401
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The aim of our study was to investigate the expression of MAC30 mRNA and its correlation with clinicopathological variables in human colorectal cancer (CRC). Methods: MAC30 mRNA expression was first examined in 55 CRCs, along with the samples from the matched distant normal and adjacent noncancerous tissue by RT-PCR, further verified in 18 CRCs by quantitative RT-PCR. MAC30 protein expression was detected by Western blot in 10 CRCs, and DNA sequencing was performed in 1 case of the paired CRC and the matched noncancerous specimen. MAC30 mRNA expression in two colon cancer cell lines, HCT-116(p53-/-) and HCT-116(p53+/+), was detected by quantitative RT-PCR. Results: The mRNA expression of MAC30 was increased in CRC when compared with distant normal (p < 0.01) and adjacent noncancerous mucosa (p < 0.01). The mean value of MAC30 mRNA expression in the tumor located in the colon was higher than in the rectum (0.677 +/- 0.419 vs. 0.412 +/- 0.162, p = 0.005). As the tumor penetrated the wall of the colon/rectum, MAC30 mRNA expression notably increased in tumors with T3+T4 stage compared to tumors with T1+T2 stage (0.571 +/- 0.364 vs. 0.404 +/- 0.115, p = 0.014). MAC30 protein expression in CRCs was also remarkably elevated compared to the adjacent noncancerous mucosa. There was no mutation in the coding region of the MAC30 gene either in CRC or in the noncancerous mucosa. mRNA expression of p53 was notably decreased in HCT-116(p53-/-) compared to HCT-116(p53+/+), while MAC30 did not vary greatly. Conclusion: The overexpression of MAC30 might be involved in the development and aggressiveness of CRCs, especially in the colon.
|
|
| 9. |
- Zhu, Zhen-Long, et al.
(författare)
-
Cytoplasmic expression of p33(ING1b) is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma.
- 2013
-
Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 161-166
-
Tidskriftsartikel (refereegranskat)abstract
- p33(ING1b), a newly discovered candidate tumor suppressor gene and a nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33(ING1b) has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies. Since little is known about the clinicopathological significance of p33(ING1b) in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC. p33(ING1b) expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33(ING1b) protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0.0001). Furthermore, the cases with lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P=0.001). The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P<0.0001) in ESCC, and the cases positive for both proteins had a high lymph node metastasis rate (P=0.001). In conclusion, p33(ING1b) cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the tumorigenesis and metastasis of ESCC.
|
|
| 10. |
- Zhu, Zhen-Long, et al.
(författare)
-
Expression and significance of FXYD-3 protein in gastric adenocarcinoma
- 2010
-
Ingår i: DISEASE MARKERS. - : Ios Press. - 0278-0240. ; 28:2, s. 63-69
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma. Patients and methods: FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n = 29) and gastric adenocarcinoma (n = 51), obtained from surgical resection of gastric cancer patients. Results: FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X-2=13.210, p andlt; 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X-2 = 5.765, p = 0.016). However, FXYD-3 expression was not correlated with patients gender, age, tumor size, lymph node status and histological grade (p andgt; 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma.
|
|
