| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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| 2. |
- Zhang, Hong-Zhen, et al.
(författare)
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PINCH Protein Expression in Normal Endometrium, Atypical Endometrial Hyperplasia and Endometrioid Endometrial Carcinoma
- 2010
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Ingår i: CHEMOTHERAPY. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 56:4, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- Background: Particularly interesting new cysteine-histidine rich protein ( PINCH), as an adapter protein of the LIM family for signal transduction in the integrin and growth factor pathway, is upregulated in the stroma of several common types of cancers and involved in promoting tumor progression. In the present study, we examined PINCH expression in normal endometrium, atypical endometrial hyperplasia and endometrioid carcinoma, and further studied the relationships of PINCH expression with clinicopathological variables in cancer patients. Methods: PINCH expression was examined by immunohistochemistry in 23 normal endometrial samples, 18 atypical endometrial hyperplasias and 48 endometrioid endometrial carcinomas. Results: The PINCH expression in the stroma of cancer (71%) was significantly increased compared to either normal endometrium (17%, p andlt; 0.0001) or atypical hyperplasia (39%, p = 0.017), along with 9 cancers that had stronger PINCH expressions at the invasive margin of the cancers compared to the inner cancers. PINCH expression in cancer was higher in the patients with hypertension (p = 0.041) and estrogen exposure time andgt;30 years (p = 0.021). On the other hand, PINCH expression was not related to menopausal status, gravid status, blood sugar/lipid, family background of cancer, histological grade, myometrial invasion, cervical involvement, lymph nodal metastases, growth pattern, estrogen and progestogen receptors (p andgt; 0.05). Conclusion: The results suggest that PINCH seems to play a role, presently unknown, in the tumorigenesis and development of endometrial cancer that merits further study.
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| 3. |
- Zhu, Zhen-Long, et al.
(författare)
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Cytoplasmic expression of p33(ING1b) is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma.
- 2013
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Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 161-166
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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.
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| 4. |
- Zhu, Zhen-Long, et al.
(författare)
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PINCH expression and its clinicopathological significance in gastric adenocarcinoma
- 2012
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Ingår i: Disease Markers. - : IOS Press. - 0278-0240 .- 1875-8630. ; 33:4, s. 171-178
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma. less thanbrgreater than less thanbrgreater thanPatients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n = 30) and gastric adenocarcinoma (n = 73), from gastric cancer patients. less thanbrgreater than less thanbrgreater thanResults: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X-2 = 9.711, p = 0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X-2 = 11.151, p = 0.001). PINCH expression was not correlated with patients gender, age, tumour size, differentiation and invasion depth (p andgt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma.
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| 5. |
- Yan, Bao-Yong, et al.
(författare)
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Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation
- 2010
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Ingår i: Chemotherapy. - : S, Karger AG, Basel. - 0009-3157 .- 1421-9794. ; 56:6, s. 424-428
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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.
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| 6. |
- Zhu, Zhen-Long, et al.
(författare)
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Expression and significance of FXYD-3 protein in gastric adenocarcinoma
- 2010
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Ingår i: DISEASE MARKERS. - : Ios Press. - 0278-0240. ; 28:2, s. 63-69
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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.
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| 7. |
- Zhu, Zhen-Long, et al.
(författare)
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Overexpression of FXYD-3 is involved in the tumorigenesis and development of esophageal squamous cell carcinoma
- 2013
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Ingår i: Disease Markers. - : IOS Press. - 0278-0240 .- 1875-8630. ; 35:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association of FXYD-3 expression with clinicopathological variables and PINCH in patients with ESCC.Patients and methods: Expression of FXYD-3 protein was immunohistochemically examined in normal esophageal mucous (n = 20) and ESCC (n = 64). Results: Expression of FXYD-3 in the cytoplasm markedly increased from normal esophageal epithelial cells to primary ESCC ( p = 0.001). The expression of FXYD-3 was correlated with TNM stages and depth of tumour invasion. Furthermore, the cases with lymph node metastasis tended to show a higher frequency of positive expression than those without metastasis ( p = 0.086), and FXYD-3 expression tended to be positively related to the expression of PINCH (p = 0.063). Moreover, the cases positive for both proteins had the highest frequency of lymph node metastasis (p = 0.001). However, FXYD-3 expression was not correlated with patient,s gender (p = 0.847), age (p = 0.876), tumour location (p = 0.279), size (p = 0.771) , grade of differentiation (p = 0.279), and survival (p = 0.113).Conclusion: overexpression of FXYD-3 in the cytoplasm may play an important role in the tumourigenesis and development in the human ESCC, particularly in combination with PINCH expression.
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