Advances in cancer biology - metastasis最新文献

Cervical cancer (CC), the fourth worldwide incessant malignant neoplasia particularly in women, emerged as a serious public health problem. Metabolic syndrome (MetS) is an accumulation of different threats aspects, which could eventually cause diabetes and cardiovascular disease as co-morbidity, further contributing to mortality that is detected by central obesity, dyslipidemia, hyperglycemia, and hypertension. Accumulatively, endemic as well as research data supports the notion of MetS increasing general malignancies occurrences, further contributing to mortality rate. Nano-scale drug delivery system, provide targeted drug delivery, increases drug absorption rates, while drug decomposition and systemic adverse effects get decreased. This article has described the different metabolic syndromes playing role in cervical cancer, alongside cervical cancer nanocarriers modern therapy.

Background

Baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, member of the inhibitor of apoptosis (IAP), is a multitasking protein and among the top 100 deregulated genes in breast cancer patients. It negatively regulates apoptosis of tumor cells by inducing gene expression of anti-apoptotic proteins, promoting tumor cell proliferation, and modulates response to chemotherapeutics.

Objective

The main objective of the study was to analyze the expression pattern, prognostic significance and functional role of BIRC5 in breast cancer (BC).

Methods

In the present study, we utilized a bioinformatic approach, to analyze the expression pattern and prognostic significance of BIRC5 in BC and explore the interactions of BIRC5 in promoting breast tumorigenicity.

Results

BIRC5 mRNA levels were augmented in breast carcinoma & over-expression of BIRC5 was found associated with poor overall survival (OS) and relapse-free survival (RFS). The KEGG pathway and gene ontology analysis of BIRC5 indicate that BIRC5 is highly enriched in mitotic pathways and cancer pathways. The PPI and correlation analysis further revealed that BIRC5 showed high with oncogenic proteins. Moreover, BIRC5 showed high correlation with infiltration of myeloid derived suppressor cells (MDSCs) in the breast tumor stroma.

Conclusions

Cumulatively, this study signifies that BIRC5 promotes tumor progression, & targeting BIRC5 in combination with conventional therapies will significantly enhance the response of BC patients to therapy.

Ras signaling contributes to multiple components of cellular functions. To gain insight into the role of KRAS mutant isoforms, we bioinformatically analyzed and noticed that KRAS mutations at G12V, G12D, and G13D positions are prominent in colorectal adenoma and carcinoma. The bioinformatic analysis indicates that KRAS mutations affect MAPK signaling cascades despite other signaling pathways. Lipid rafts orchestrate many signaling pathways on the plasma membrane and one of those works via the RAS/ERK axis to activate gene expression. Herein, we show that lipid raft-RAS/ERK modulates gene expression by differentially altering active H3K4me3 and H3K9acS10P, and repressive H3K9me3 and H3K27me3 marks, and further, we have deciphered distinct expression pattern of Caveolin-1 (CAV1) in constitutive KRAS versus lipid raft disruption induced KRAS signaling in colon cancer cells, HCT-15. CAV1 gene expression is upregulated by differential enrichment of H3K4me2, H3K4me3, and H3K9acS10p, depending on which component of the lipid raft/RAS/ERK axis is blocked. The enhancement of transcription of the CAV1 gene is associated with very high occupancy of H3K4me3 and H3K9acS10p and very low H3K9me3 marks in its promoter region. Thus we conclude that genetic mutation in KRAS and distinct association of lipid raft with KRAS contributes to colon cancer progression; however, lipid raft association/dissociation regulates the paradoxical function of genes, for example, CAV1, by epigenetic modulations.

Papaya (Carica papaya) is a fruit that grows mainly in tropical areas with significant commercial worth due to its extraordinary nutritional and therapeutic value. Its fruit, leaves, and seeds are used as a traditional medicine in India for various ailments, including cancer. Papaya fruit was always a treatment choice among traditional ayurvedic practitioners for various ailments. The usage of papaya leaf extract for curing dengue fever had gained popularity at the time of severe dengue outbreak in various Asian countries, including India. Studies had proved that papaya leaf extract can increase platelet count and improve dengue patients' health conditions. However, the usage of papaya seeds for treatment has not gained much popularity even though it has been widely recommended in ancient Ayurvedic texts. In this study, we have tried to assess the anticancer potential of papaya black seeds, which are present in the ripe papaya fruits. The “methanolic extract of papaya black seeds” (MPB) ¹have been studied for the in vitro cytotoxicity against the human liver cancer Hep G2 cell lines. The half maximal inhibitory concentration (IC₅₀) value was quantified using the 3-(4,5-dimethylthiazoline-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Along with this, the apoptotic changes on the cancer cells induced by MPB have been assessed with the help of Acridine Orange-Ethidium Bromide (AO-EB) staining. The regulation of gene expression has been evaluated by targeting B cell Lymphoma -2 (Bcl-2), p53, and Caspase-3 genes by relative gene expression studies via quantitative Real Time Polymerase Chain Reaction (qRT PCR). From this study, we have concluded that papaya black seeds may be a prospective therapeutic agent in liver cancer therapy with an IC₅₀ value of 24.35 ​μg/mL along with the potential to induce apoptotic changes by downregulating the Bcl-2 and upregulating p53 and Caspase-3 genes.

Generally, bacteria cause infectious diseases. The role of bacteria as a causative agent of oncogenesis or mediators has been less known and elucidated. To date, Helicobacter pylori and Chlamydia pneumonia were identified and reported as cancer-causing bacterial pathogens. Research reports also indicated Salmonella typhi as oncogenic bacteria that alter the human immune system and establishes gall bladder cancer (GBC). S. typhi releases the carcinogenic toxic molecules at the chronic phase with the asymptomatic sign and facilitates the process of transformation of normal cells into the carcinogenic cell. S. typhi infection may work as a key indicator for future GBC and lethality in planktonic conditions. The clinician identified the typhoid infection and break down the association at the primary stage in GBC. This article contains the relationship between gallbladder cancer and S. typhi and gets attention in the field of oncology because pathogen may work as a carcinogen. Because the pathogenic drive cancer field is not fully described.

Cancer during pregnancy is a rare event in the realm of obstetric statistics. Stem cells are known for their capability to renew their demographic to a variety of cell lineages. Embryonic stem cells (ESCs) originating from the blastocyst include haematopoietic stem cells (HSC) and mesenchymal stem cells (MSC). These cells play vital roles in the complex course of fetal growth and development. MSCs are found to suppress tumour growth by inhibiting PI3K/AKT pathway. Although a notable amount of literature is available about the occurrence of cancer during pregnancy, there is a lacuna about the interaction between the fetal stem cell (FSCs) and the cancer cells. A literature review revealed that the risk of ovarian cancer is reduced with an increase in fetal stem cells. After delivery, fetal microchimerism is observed to promote or suppress tumour growth under specific conditions. This review highlights the mechanism and extent of the association of FSC with the occurrence of various cancers during pregnancy. A new perspective on mother to fetus cancer transmission, which is commonly leukemia and melanoma, and the reasons for FSCs to respond differently to these cancers under various conditions have been identified by analyzing recent pieces of literature. This review also gives an idea about the existing and probable therapeutic benefits obtained from the FSCs in curbing the extent of maternal tumour metastasis. Stem cells are presently being manipulated to consistently express different chimeric antigen receptors or T cell receptors, countering tumour-associated antigens. Thus, this study highlights the therapeutic potential of the interesting crosstalk against haematological malignancies and solid tumours.

Overview

The liver is a vital organ, performing over 500 functions. Metastasis to the liver can disrupt these functions, resulting in poor prognoses. It is not always clear why liver metastasis arises in one case but not another involving the same cancer type. We sought to understand which transcripts and cellular pathways are dysregulated in cell lines shown to metastasize substantially to the liver in a NOD-Scid-Gamma (NSG) mouse-xenograft model. Cancer cell lines of the same type not observed to metastasize to the liver were used for comparison, reducing cell type-specific changes or general pathways associated with cancer not linked to liver metastasis. Three metastatic versus non-metastatic pairs of diverse origin–Merkel cell, colorectal, and pancreatic carcinomas–as well as a normal fibroblast control were used for deep sequencing and transcriptome analysis with subsequent pathway identification.

Results

Dysregulated pathways involve cell adhesion, proliferation, and motility (among others), which are consistent with increased malignant potential in the cell lines that support liver metastasis. In addition, dysregulated peroxisome proliferating activated receptor (PPAR) signaling and lipid metabolic / trafficking pathways are candidates for fostering homing to the liver. A surprise was a significant drop in AGR2 expression in cells favoring liver metastasis, while still remaining elevated relative to normal fibroblast controls. Newer clinical data revealed declining levels of AGR2 correlate with higher grade lesions and poorer prognoses in patients with various cancer types. Decreased expression of FOXA2 similarly correlates with clinical data as a prognostic factor. A drop in FOXA2 expression was observed in cell lines favoring liver metastasis, as well as a cell line generated from an NSG-xenograft liver metastasis, which may also explain the liver site preference of select cancer cell lines. Both genes correlate with PPAR signaling dysregulation and either directly or indirectly link to such pathways. Meanwhile, LOXL2 is lower in the cancer cell lines supporting liver metastasis compared to normal fibroblasts, but is substantially elevated relative to paired cancer cell lines which did not metastasize to the liver. LOXL2 is a gene involved in epithelial-mesenchymal transition (EMT), which is expressed at high levels in both normal and cancer-associated fibroblasts.

Conclusions

Using only a normal fibroblast control for comparison, or only comparing cancer cells as separate pairs, would have masked several potential candidate genes and pathways linked to liver metastasis. Our findings correlate well with newer clinical data and reinforce biomarkers of disease progression. The dysregulated genes and pathways highlight potential targets to slow disease progression.

Epithelial-to-mesenchymal transition (EMT) is a key cellular process involved in the various biological processes ranging from embryonic development, wound healing, and cancer metastasis. EMT is the key player in cancer progression to a metastatic state. The transformed tumor cells acquire the migratory property and invade surrounding tissues, which ultimately leads to cancer metastasis via EMT. Epithelial cells undergo certain phenotypic changes to acquire mesenchymal status. At a molecular level, this transition process is elicited by several signaling cascades that include cytokines and a group of transcription factors like Twist, snail, and Zeb1/2. Emerging evidence suggests that various non-coding RNAs (ncRNAs) play a significant role in modulating EMT-associated transcription factors (EMT-TFs) and molecular signaling at the transcriptional and post-transcriptional level and thus, regulating the EMT process. Various noncoding-RNAs like miRNAs, piRNAs, tsRNAs, lncRNAs, T-UCRs, CircRNAs, eRNAs, snoRNAs can either promote or can inhibit the process of EMT and thus modulates cancer progression. Here we review the recent research advances in delineating the role of various non-coding RNAs in the EMT, cancer, and metastasis process as well as their potential roles as biomarkers and therapeutic targets.

Lung cancer is the leading cause of death; by the time it is diagnosed, the patient is usually in late-stage grade IV. Late-stage lung cancer is mainly associated with metastasis in the liver, brain, and lymphoid tissues; as a result, a localized lung cancer treatment remains meaningless. Early diagnosis of non-small cell lung cancer (NSCLC) may be curable or will improve the survival rate. Although with advanced developments to screen high-risk patients by LDCT scan, false-positive rates and limited resolution necessitated the development of advanced diagnostic techniques for NSCLC. Extracellular vesicles (EVs) released from cells freely circulate in the blood and contain various transmembrane proteins, and they may be a non-invasive biomarker for cancer diagnosis and prognosis. Current studies predict that the CD91 marker in EVs may be a potential biomarker of NSCLC; however, the expression of CD91 in lung cancer tissues is not fully known. Here, this study determines the differential expression of CD91 in lung cancer cells and in circulating EVs in blood as a potential biomarker of NSCLC patients. Our results confirmed the expression of CD91 in NCI–H1975 cultured cells and NSCLC lung biopsy tissues. Furthermore, biophysical characterization of EVs from lung cancer cells determines the substantial expression of CD91, which the Transmission Electron Microscope confirms. Thus, this study suggests EVs containing CD91 could be an asset to studying the development of diagnostic and prognostic biomarkers in NSCLC disease.