Novel Carbazole-Piperazine Hybrid Small Molecule Induces Apoptosis by Targeting BCL-2 and Inhibits Tumor Progression in Lung Adenocarcinoma in Vitro and Xenograft Mice Model.
These data suggest that, in endometrial carcinomas, Bcl-2 and p53 alterations may play important roles in determining whether tumor progression from early to advanced stages will occur.
This provides evidence that Bcl-2 plays a role in tumor progression of glioma by acting as an oncogene, and suggests that inhibition of the bcl-2 gene could have a therapeutic effect.
Our results further revealed that NRP-1 knockdown decreased the expression levels of Bcl-2 family proteins and deactivated extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling pathways, closely associated with cancer progression.
Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure.
Interaction between p53, Bcl-2, and other products of tumor suppressor genes or oncogenes are probably critical in tumor progression and response to treatment.
One patient with follicular small cleaved cell NHL that evolved to a small noncleaved cell NHL had coexisting bcl-2 and c-myc rearrangement in the aspiration specimen of the high-grade NHL, suggesting sequential bcl-2 and c-myc activation during the tumor's progression.
Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients.
Thus, acquisition of Bcl-2 expression is as advantageous for tumor cell growth in vivo as is p53 inactivation but does not affect genomic stability and creates the environment restrictive for the expansion of genetically unstable and potentially malignant p53-deficient cells, causing a delay in tumor progression and explaining the different prognostic value of Bcl-2 and p53.
Bcl-2 expression in TCC of the bladder seems to be associated with a less aggressive phenotype and does not play an important role in tumour progression.
Altered expression of Bcl-2 family proteins has been associated with tumorigenesis and tumor progression as well as resistance to radiotherapy and chemotherapy.
Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterations and facilitate tumor progression.Mutant p53 has a similar effect.
We conclude from our results that bcl-2 protein is expressed by benign and malignant melanocytic tumors of the skin, but there is loss of bcl-2 protein expression with increasing tumor progression.
The knockdown of XIAP, BCL2 and BCL-X(L) by siRNAs represents a promising treatment option for bladder cancer (BCa) since the overexpression of antiapoptotic genes is often associated with tumor progression and treatment resistance.
Bcl-2 is a prime target for novel therapeutics because it is elevated in many forms of cancer and contributes to cancer progression and therapy resistance based on its ability to inhibit apoptosis.
In SCRT, long break in the treatment should be avoided because correlation between Ki-67, KU70, and BCL-2 expressions and pTNM after RT might indicate tumor progression.
We conclude that, in contrast to its role in gastric neoplasia, bcl-2 alterations are not an important molecular marker in the neoplastic progression of Barrett's mucosa.
Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.
It is also suggested that the effect of alteration of bcl-2 expression might be minimal during the tumor progression stage because of the reduced expression in tumors of the clear cell type, which is the most dominant cell type in RCC.
The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses.