scholarly journals Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6226
Author(s):  
Zahra Pezeshkian ◽  
Stefania Nobili ◽  
Noshad Peyravian ◽  
Bahador Shojaee ◽  
Haniye Nazari ◽  
...  

Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Jiang ◽  
Yue Kang ◽  
Tomasz Sewastianik ◽  
Jiao Wang ◽  
Helen Tanton ◽  
...  

AbstractColorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.


2004 ◽  
Vol 14 (2) ◽  
pp. 333-340 ◽  
Author(s):  
J. Argüello-Ramírez ◽  
E. PÉREZ-CÁRDENAS ◽  
R. Delgado-Chávez ◽  
G. Solorza-Luna ◽  
S. Villa-Treviño ◽  
...  

Elevated expression of matrix metalloproteinases (MMPs) plays a critical role in extracellular matrix (EM) degradation in tumor development and prognosis of different human carcinomas. In cervical carcinoma (Ce Ca), the role of these proteinases in the biological development of this neoplasm is controversial. In the present study, we compared the secretion of MMP-2, MMP-3 and MMP-9 among 29 benign and premalignant cervical lesions (cervicitis and cervical intraepithelial neoplasias) and 46 tumoral explants of Ce Ca. The explants were cultured for 48 h. The gelatinases secreted into conditioned medium were revealed by zymography and quantified by densitometry. The results showed high levels of MMP-3 and MMP-9 in tumoral explants. In contrast, only the pro-MMP-2 was higher in benign cervical lesions, although both active and inactive MMP-2 species are associated with advanced clinical stages in tumoral samples, and only the secretion of MMP-3 was associated with unresponsiveness to radiotherapy. We can conclude that the expression of MMPs is related to the invasive process in Ce Ca and suggest that they may play a role in degradation of the EM during local invasion. In addition, MMP-3 secretion could be a marker of poor prognosis in Ce Ca.


2021 ◽  
Author(s):  
Xinfang Yu ◽  
Li Zhou ◽  
Wenbin Liu ◽  
lijun Liu ◽  
Feng Gao ◽  
...  

Abstract Background Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. Methods The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Results Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of Skp2 confers sensitivity to irradiation of CRC cells. Skp2 deficiency enhances irradiation-induced intrinsic apoptosis by facilitating E3 ligase FBW7-mediated Mcl-1 ubiquitination and degradation. Knockout of Skp2 sensitizes CRC cells to irradiation treatments in vivo. Conclusion Our findings indicate that Skp2 stabilizes Mcl-1, and targeting Skp2 in combination with traditional radiotherapy might be efficacious in treating CRC.


2020 ◽  
Vol 30 (6) ◽  
pp. 509-518
Author(s):  
Zengtao Bao ◽  
Shanting Gao ◽  
Baoming Zhang ◽  
Wenchao Shi ◽  
Aimin Li ◽  
...  

2013 ◽  
Vol 1 (1) ◽  
pp. 64 ◽  
Author(s):  
Pranam Dhar

Zakat is an important form of religiously mandated charity under Islam. It is the third pillar of Islam. The giving of Zakat is important for Muslims, as this leads to purification of their wealth from all sins. This paper examines the role of Zakat as an instrument of social justice and poverty eradication in society. Each Muslim calculates his or her own Zakat individually. Generally, this involves the payment each year of two and a half percent of one's capital, after the needs of the family have been met. One can donate additional amount as an act of voluntary charity but Zakat is fundamental to every Muslim. Zakat is the Islamic contribution to social justice: those who have to give charity share the benefit of their prosperity to those who have fallen short. This is the Islamic approach to remove greed and envy and to purify one's soul based on good intentions. This is the institution of Zakat in Islam. The institution of Zakat serves to eradicate poverty in the community and uphold the light of Islam. Allah says “whatever is paid as Zakat for the sake of Allah shall be rewarded in manifolds”.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.


2021 ◽  
pp. bmjspcare-2021-002971
Author(s):  
Moshe Y Flugelman

Informing families about the impending or actual death of their relatives is one of the most challenging and complex tasks a physician may face. The following article describes goal setting and provides five roles/recommendations for conducting the encounter with patient families regarding the imminent or actual death of their relatives. Importantly, the encounter should be family-centred, and the physician should be highly attentive to family needs. The following roles should be applied based on family needs and should not be sequential as numbered. The first and basic role is to inform the family at the earliest possible time and as often as possible. The second goal of the physician is to convey to the family that their relative received the needed therapy during his hospitalisation or in the community. The third goal of the physician is to help the family reach acceptance of the death of their relative and leave the hospital having moved beyond anger and bargaining. The fourth goal of the physician during the encounters is to reduce or alleviate guilt by stating that nothing could have changed the course of the disease and that all efforts were made to save the patient. The fifth role of the physician is to try and help the family as a single entity and maintain their unity during this stressful situation. Following these roles/methods will help families in the stressful situation and will create the difference between anger and understanding, rage and compassion, and loss and acceptance.


2021 ◽  
pp. 252-268
Author(s):  
V. V. Dyachkov ◽  

The paper deals with the grammaticalization problems in Tomo Kan (Dogon family, Niger-Congo) and, in particular, with the diachronic relationship of polypredicative constructions and TAM markers. Dogon languages are characterized by TAM systems that seem to be dia-chronically unstable since markers with a similar range of meanings go back to different lexi-cal sources in different languages of the family. TAM markers are apparently associated with polypredicative constructions, which are very common in Dogon and preserve some of their morphosyntactic properties. At the same time, Dogon languages are characterized by complex tonal changes triggered not only by phonological context but also by the syntactic position of constituents. These tonal changes, frequently referred to as tonosyntax, accompany the formation of polypredicative constructions and other syntactic phenomena. A thorough inves-tigation of Tomo Kan TAM markers shows their tonosyntactic properties to resemble those of polypredicative constructions. Moreover, assuming that tonosyntax of polypredicative con-structions triggers certain tonal contour overlays, one can account for tonal alternations ob-served in TAM forms which would have been left otherwise unexplained. However, the anal-ysis also reveals that at least two classes of TAM forms must be distinguished in Tomo Kan: one of them inherits the tonosyntax of polypredicative constructions while the other does not. A hypothesis is put forward that the latter class has a different source of grammaticalization and is probably associated with verb stem incorporation rather than with polypredication. Methodologically, the paper shows a critical role of tonology in the analysis of grammaticalization processes in tonal languages.


Archaea ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Yanli Zhang ◽  
Linley R. Schofield ◽  
Carrie Sang ◽  
Debjit Dey ◽  
Ron S. Ronimus

(R)-Sulfolactate dehydrogenase (EC 1.1.1.337), termed ComC, is a member of an NADH/NADPH-dependent oxidoreductase family of enzymes that catalyze the interconversion of 2-hydroxyacids into their corresponding 2-oxoacids. The ComC reaction is reversible and in the biosynthetic direction causes the conversion of (R)-sulfolactate to sulfopyruvate in the production of coenzyme M (2-mercaptoethanesulfonic acid). Coenzyme M is an essential cofactor required for the production of methane by the methyl-coenzyme M reductase complex. ComC catalyzes the third step in the first established biosynthetic pathway of coenzyme M and is also involved in methanopterin biosynthesis. In this study, ComC fromMethanobrevibacter milleraeSM9 was cloned and expressed inEscherichia coliand biochemically characterized. Sulfopyruvate was the preferred substrate using the reduction reaction, with 31% activity seen for oxaloacetate and 0.2% seen forα-ketoglutarate. Optimal activity was observed at pH 6.5. The apparentKMfor coenzyme (NADH) was 55.1 μM, and for sulfopyruvate, it was 196 μM (for sulfopyruvate theVmaxwas 93.9 μmol min−1 mg−1andkcatwas 62.8 s−1). The critical role of ComC in two separate cofactor pathways makes this enzyme a potential means of developing methanogen-specific inhibitors for controlling ruminant methane emissions which are increasingly being recognized as contributing to climate change.


2021 ◽  
Vol 22 (16) ◽  
pp. 8470
Author(s):  
Hui Wang ◽  
Tian Tian ◽  
Jinhua Zhang

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.


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