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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Due to the existence of gravel, glutenite is heterogeneous and different from fine-grained rocks such as sandstone and shale in structure. To fully understand the effect of gravel on failure mode in glutenite, we performed triaxial compression tests on different glutenites. The results indicate that failure modes of glutenite are complex due to the existence of gravel. Under different confining pressures, three failure modes were observed. The first failure mode, a tensile failure under uniaxial compression, produces multiple tortuous longitudinal cracks. In this failure mode, the interaction between gravels provides the lateral tensile stress for rock splitting. The second failure mode occurs under low and medium confining pressure and produces a crack band composed of micro-cracks around gravels. This failure mode conforms to the Mohr-Coulomb criterion and is generated by shear failure. In this failure mode, shear dilatancy and shear compaction may occur under different confining pressures to produce different crack band types. In the second failure mode, gravel-induced stress concentration produces masses of initial micro-cracks for shear cracking, and gravels deflect the fracture surfaces. As a result, the fracture is characterized by crack bands that are far broader than in fine-grained rocks. The third failure mode requires high confining pressure and produces disconnected cracks around gravels without apparent crack bands. In this failure mode, the gravel rarely breaks, indicating that the formation of these fractures is related to the deformation of the matrix. The third failure mode requires lower confining pressure in glutenite with weak cement and matrix support. Generally, unlike fine-grained rocks, the failure mode of glutenite is not only controlled by confining pressure but also by the gravel. The failure of glutenite is characterized by producing cracks around gravels. These cracks are produced by different mechanisms and distributed in different manners under different confining pressures to form different fracture patterns. Therefore, understanding the rock microstructure and formation stress state is essential in guiding glutenite reservoir development. [ABSTRACT FROM AUTHOR]

Objective: Identification of novel biomarkers and related molecular pathways are critical for understanding the underlying biology of human malignancies, as well as to design effective cancer therapeutics. MicroRNAs (miRNAs) are classified as a kind of short non-coding RNAs that interfere with specific target mRNAs and therefore regulate multiple biological processes. We characterized here the expression and function of miR-542-3p in esophageal squamous cell carcinoma (ESCC). Methods: Real-time PCR was used to examine the miR-542-3p expression. After transfections of its synthetical mimics or inhibitor, cell growth rate was explored by cell counting assay. In addition, its expression was further statistically analyzed to reveal its association with clinical characters. Results: We show that miR-542-3p, a well-characterized tumor suppressor was significantly decreased in ESCC tissues and cell lines, whose downregulation is tightly associated with tumor grade. Furthermore, forced expression of miR-542-3p suppressed cell proliferation, while silencing its expression by a synthetical inhibitor could enhance cell growth rate. Conclusion: Taken together, our results indicated that miR-542-3p is a tumor suppressor of esophageal cancer acting at steps that regulate cell growth. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present investigation was to study the clinical significances of the abnormal expressions of Piwil1 and Piwil2 protein in colonic adenoma and adenocarcinoma. Methods: This study had applied immunohistochemical method to detect 45 cases of tissues adjacent to carcinoma (distance to cancerous tissue was above 5 cm), 41 cases of colonic adenoma and 92 cases of colon cancer tissues, and their Piwil1 and Piwil2 protein expression levels. Analysis: The correlation of both expression and its relationship with clinicopathological features of colon cancer was analyzed. Results: Positive expression rates of Piwil1 in tissues adjacent to carcinoma, colonic adenoma, and colon cancer were 11.1% (5/45), 53.7% (22/41), and 80.4% (74/92), respectively; the expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05). In each group, the positive expression rates of Piwil2 were 24.4% (11/45 cases), 75.6% (31/41 cases), and 92.4% (85/92 cases); expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05). Piwil1 expression and the correlation of the degree of differentiation, TNM stage, and lymph node metastasis were statistically significant (P<0.05). Piwil2 expression and the correlation of the degree of differentiation, tumor node metastasis (TNM) stage, and lymph node metastasis had no statistical significance (P>0.05). In colon cancer tissue, Piwil1 and Piwil2 expressions were positively correlated (r=0.262, P<0.05). Conclusion: The results showed that the abnormal expression of Piwil1 and Piwil2 might play an important role in the process of colon cancer development. [ABSTRACT FROM AUTHOR]

Objective: The relationship between microRNA (miR-146a) rs2910164G/C polymorphism and gastrointestinal cancer susceptibility is not consistent with each other of the published articles. The aim of this meta-analysis was to acquire a more precise effect of the association between the miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer. Materials and Methods: Through searching of the MedLine, Embase, China National Knowledge Infrastructure, and Wanfang databases. Case-control or cohort studies about the relationship between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility were screened and included in this meta-analysis. Quantitative data synthesis was conducted for the associations of miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer risk by statistical software STATA-11.0. Results: Ten studies including 6473 gastrointestinal cancer patients and 7923 controls were identified and included in this meta-analysis. For recessive genetic model (CC vs. CG + GG), people with CG or GG is associated with the susceptibility of gastrointestinal cancer compared with genotype of CC (R = 0.73, 5% confidence interval [CI]: 0.55-0.97, [P= 0.03]); But for dominant model (CC + CG vs. GG) and homozygous model (CC vs. GG), no association of the miR-146a rs2910164G/C polymorphism and gastrointestinal cancer susceptibility were found (dominant: Odds ratio [OR] =0.94, 95% CI: 0.82-1.03, [P= 0.37]; homozygous: OR = 0.85, 95% CI: 0.71-1.03, [P= 0.10]). Sub-group analysis, for homozygous model, people with GG genotype had increased risk of developing colorectal cancer (OR = 0.77, 95% CI: 0.6 4-0.93, [P= 0.008]). Conclusion: No significant association between miR-146a rs2910164G/C polymorphism and gastrointestinal cancer susceptibility was found in this meta-analysis. But for homozygous model, people with GG genotype may have increased risk of developing colorectal cancer. [ABSTRACT FROM AUTHOR]