Advances in cancer biology - metastasis最新文献

Cancer is one of the major health burdens in modern world, and its mechanism is very complex, which is one of the main reasons for difficulties in cancer drug development. The development of cancer is associated with chronic inflammation, although inflammation is an essential biological process. The epithelial-mesenchymal transition (EMT) is a crucial step in development process of human tissue and involve in the regulatory pathways. On the contrary, the uncontrolled EMT is responsible for the initiation of cancer, its metastasis, immunosuppression, and resistance to antitumor treatment. Interestingly, there is an interrelationship between inflammation and EMT process. Usually, proinflammatory cytokines activate EMT inducing transcription factors (EMT-TFs), causing epithelial cells to change into cancerous mesenchymal cell by activating the mesenchymal cells markers, such as N- Cadherin, Fibronectin, Vimentin etc., and inhibiting the epithelial cells markers such as E− Cadherin, Claudin 1, Occludin, and β-catenin. Consequently, epithelial cells are dissociated, invasive, motile, resistant to therapy, resistant to apoptosis, and undergo mesenchymal cells angiogenesis. Some natural products and short RNAs have been identified to interfere with inflammation-EMT axis to inhibit cancer progression and metastasis. We have described these relationships in this review article and also described the therapeutic perspectives for cancer.

Background

Colorectal carcinoma (CRC) is the third most common cancer in the world and incidences are on the rise in Bangladesh. KRAS, NRAS, BRAF, PIK3CA, and AKTI gene mutations are predictive markers of biological therapies, monoclonal antibodies targeting EGFR. The purpose of this study was to detect KRAS, NRAS, BRAF, PIK3CA, and AKT1 genes mutation in CRC patients by multiplex real-time Polymerase Chain Reaction (PCR) and evaluate the association of the mutations with clinicopathological features.

Methodology

This cross-sectional study was carried out in the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2019 to January 2020. Tissues from surgically resected colorectal tumors were collected from 44 histopathologically confirmed adult colorectal cancer patients, who were admitted in the Department of Colorectal Surgery, BSMMU.

Results

Among 44 histopathologically diagnosed colorectal cancer patients, KRAS, BRAF, and PIK3CA gene mutations were identified in 31.5%, 4.85%, and 4.85% tumors, respectively. In this study, no mutation was detected in NRAS and AKT1 genes. Concurrent mutation in KRAS and PIK3CA genes were found in one patient. Among the 14 KRAS mutant cases, most (92.85%) were in exon 2 (codon 12/13) and only 7.15% of the mutations were in exon 3 (codon 61). No mutation was detected in codon 59, 117, and 146. Among the two PIK3CA mutations, one was present in exon 9 and another was in exon 20. KRAS mutations were significantly associated with well and moderately differentiated tumors than poorly differentiated tumors (p < 0.05). Histopathologically there was no significant association of KRAS mutations with age, sex, tumor location, TNM staging, and other parameters.

Conclusion

A combined evaluation of genetic biomarkers can classify about one-third of colorectal cancer patients as mutant for any one of these KRAS, BRAF, and PIK3CA genes.

Cancer is a global challenge for healthcare professional due to multiple unresolved issues before therapy, during therapy, and post-therapy stages. The disease diagnosis and subsequent chemotherapy are an ideal treatment approach to culminate such menace. Among cancers, prostate cancer (PC) is considered next to skin and breast cancer as the most dreadful and recorded with high mortality. It is also one of the leading causes of cancer death among men. With increased incidence worldwide and high mortality rate prostate cancer remains a global healthcare challenge. Advances in the diagnosis of PC have improved the chances of patient survival. Today, scientists developed electrochemical biosensors for early diagnosis of PC and it was found to be playing a significant role to reduce cases, mortality and complication at clinical set up. This updated review focused on biomarkers and traditional techniques used for PC diagnosis (early) and the most recent achievements of electrochemical techniques for making successful translation to clinical bed. Nanoparticles based electro-biochemical techniques have gained considerable attention alternative to traditional techniques. These techniques are found significantly effective for PC detection and have shown interesting parameters such as low cost and easy incorporation to user-friendly sensing platforms. With further advancements portable devices can be developed that can diagnose PC earlier for rapid clinical analysis and subsequently earliest report availability to the physician office for quick decision and life-saving approach. Overall, these compiled data in a form of review paper supports the adoption and promotion of nanotechnology-based diagnostics for PC in the healthcare.

Cases of cervical cancer metastatic to the bowel are not rare because recurrent cervical cancer can commonly metastasize to nearby structures by direct extension. However, in recurrent cervical cancer patients who have received repeated radiation therapy, the treatment approach for acute abdominal pain has been generally established based on the first diagnostic impression of radiation enteritis. Therefore, we want to report with the aim of notifying that the possibility of bowel metastasis, especially in patients who have repeatedly received radiation therapy for recurrent cervical cancer, should also be considered not only for radiation enteritis. Here, we report the case which showed the clinical diagnosis of radiation enteritis after receiving repeated radiation therapy for recurrent cervical cancer, but showed the final pathologic diagnosis of bowel metastasis.

MicroRNAs (miRNAs) are actively involved in the progression and metastasis of ovarian cancer. Here we show that miR-203b–3p is one of the miRNAs whose expression is diminished in advanced ovarian cancer (Stage III/IV). Introducing miR-203b-3p into ovarian cancer cells suppressed cell migration, in vitro invasion and peritoneal metastatic colonization. With the aid of cytokine array and modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH), we identified C-X-C motif chemokine ligand 1 (CXCL1) mRNA as a target of miR-203b-3p. Recombinant CXCL1 largely restored cell migration/invasion and CXCL1 neutralizing antibody blocked cell migration/invasion. Intriguingly, miR-203b-3p targets CXCL1 in an unconventional manner: 1) miR-203b-3p targets the 5′-untranslated region (UTR) and protein coding region of CXCL1 mRNA and 2) seed sequences in miR-203b-3p are not the conventional nucleotides 2 to 8 observed for most of miRNA/target complementation. Finally, we show that epithelial cell adhesion molecule (EpCAM) aptamer can effectively deliver miR-203b-3p into ovarian cancer cells and EpCAM aptamer-delivered miR-203b-3p impeded peritoneal metastatic colonization and prolonged lifespan of tumor-bearing mice. In summary, our findings provide a novel mechanism in which attenuated miR-203b-3p expression sustains CXCL1 abundance and hence ovarian cancer progression. Importantly, we suggest that EpCAM aptamer-delivered miR-203b-3p may be exploited for therapeutic purpose against advanced ovarian cancer.

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.