scholarly journals MiR-429 Involves in the Pathogenesis of Colorectal Cancer via Directly Targeting LATS2

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xia Chen ◽  
Ai-li Wang ◽  
Yuan-yuan Liu ◽  
Chen-xi Zhao ◽  
Xue Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Solid Tumors ◽  
Therapeutic Targets ◽  
Multiple Cancer ◽  
Upstream Regulator ◽  
The World ◽  
Cancer Types ◽  
Metastasis Rate ◽  
Direct Regulator

Colorectal cancer (CRC) is a leading cause of cancer-related death around the world whose recurrence and metastasis rate is high. Due to the underlying unclear pathogenesis, it is hard so far to predict the tumorigenesis and prevent its recurrence. YAP/TAZ has been reported to be activated and functioned as a potential oncogene in multiple cancer types and proved to be essential for the carcinogenesis of most solid tumors. In the present study, we found that YAP/TAZ was markedly upregulated in CRC tissues comparing with the adjacent noncancerous tissues due to the downregulation of LATS2, the main upstream regulator. We further identified miR-429 as a direct regulator of LATS2-YAP/TAZ activation, suggesting that the miR-429-LATS2-YAP/TAZ might be novel effective diagnostic axis and therapeutic targets for CRC.

scholarly journals Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 383
Author(s):  
Jianlin Zhu ◽  
Lu Wang ◽  
Fan Liu ◽  
Jinghua Pan ◽  
Zhimeng Yao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Solid Tumors ◽  
Therapeutic Strategy ◽  
Umbilical Vein ◽  
Defined Contribution ◽  
Cancer Types ◽  
Control Tumor ◽  
Umbilical Vein Endothelial Cells ◽  
Oncogenic Protein

Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors.

scholarly journals Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiangnan He ◽  
Michelle K.Y. Siu ◽  
Hextan Y. S. Ngan ◽  
Karen K. L. Chan
Keyword(s):  
Ovarian Cancer ◽  
Mammalian Cells ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Therapeutic Targets ◽  
Multiple Cancer ◽  
Cancer Types ◽  
Characteristic Features ◽  
Rate Limiting

Cholesterol is an essential substance in mammalian cells, and cholesterol metabolism plays crucial roles in multiple biological functions. Dysregulated cholesterol metabolism is a metabolic hallmark in several cancers, beyond the Warburg effect. Reprogrammed cholesterol metabolism has been reported to enhance tumorigenesis, metastasis and chemoresistance in multiple cancer types, including ovarian cancer. Ovarian cancer is one of the most aggressive malignancies worldwide. Alterations in metabolic pathways are characteristic features of ovarian cancer; however, the specific role of cholesterol metabolism remains to be established. In this report, we provide an overview of the key proteins involved in cholesterol metabolism in ovarian cancer, including the rate-limiting enzymes in cholesterol biosynthesis, and the proteins involved in cholesterol uptake, storage and trafficking. Also, we review the roles of cholesterol and its derivatives in ovarian cancer and the tumor microenvironment, and discuss promising related therapeutic targets for ovarian cancer.

scholarly journals Circulating tumour DNA (ctDNA) as a biomarker in metachronous melanoma and colorectal cancer- a case report

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Leslie Calapre ◽  
Lydia Warburton ◽  
Michael Millward ◽  
Elin S. Gray
Keyword(s):  
Colorectal Cancer ◽  
Clinical Information ◽  
Disease Status ◽  
Cancer Type ◽  
Multiple Cancer ◽  
The Status ◽  
Cancer Types ◽  
Potential Clinical Utility ◽  
Ctdna Analysis ◽  
Circulating Tumour Dna

Abstract Background Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation. Case presentation We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF V600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient’s tumours. In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan. Based on these results, ctDNA can be used to specifically clarify disease status of patients with metachronous cancers. Conclusions Using cancer-specific mutational targets, we report here for the first time the efficacy of ctDNA to accurately provide a comprehensive outlook of the tumour status of two different cancers within one patient. Thus, ctDNA analysis has a potential clinical utility to delineate clinical information in patients with multiple cancer types.

Anticancer Immunotoxins, Challenges, and Approaches

2020 ◽  
Vol 26 ◽  
Author(s):  
Maryam Dashtiahangar ◽  
Leila Rahbarnia ◽  
Safar Farajnia ◽  
Arash Salmaninejad ◽  
Arezoo Gowhari Shabgah ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Antibody Fragment ◽  
Clinical Use ◽  
Multiple Cancer ◽  
Main Obstacle ◽  
Cancer Types ◽  
Recombinant Immunotoxins ◽  
Cancerous Cells ◽  
High Immunogenicity ◽  
Novel Therapeutic

: The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper devoted to reviewing recent advances in the design of immunotoxins with lower immunogenicity.

scholarly journals Landscape of Chimeric RNAs in Non-Cancerous Cells

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 466
Author(s):  
Chen Chen ◽  
Samuel Haddox ◽  
Yue Tang ◽  
Fujun Qin ◽  
Hui Li
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Drug Targets ◽  
Neoplastic Cell ◽  
Multiple Cancer ◽  
Chimeric Rnas ◽  
Healthy Donors ◽  
Cancer Types ◽  
Chimeric Rna ◽  
Cancerous Cells

Gene fusions and their products (RNA and protein) have been traditionally recognized as unique features of cancer cells and are used as ideal biomarkers and drug targets for multiple cancer types. However, recent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can also be found in normal cells and tissues. In this study, we aim to identify chimeric RNAs in different non-neoplastic cell lines and investigate the landscape and expression of these novel candidate chimeric RNAs. To do so, we used HEK-293T, HUVEC, and LO2 cell lines as models, performed paired-end RNA sequencing, and conducted analyses for chimeric RNA profiles. Several filtering criteria were applied, and the landscape of chimeric RNAs was characterized at multiple levels and from various angles. Further, we experimentally validated 17 chimeric RNAs from different classifications. Finally, we examined a number of validated chimeric RNAs in different cancer and non-cancer cells, including blood from healthy donors, and demonstrated their ubiquitous expression pattern.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

Characterizing the Heterogeneity of Small Extracellular Vesicle Populations in Multiple Cancer Types via an Ultrasensitive Chip

ACS Sensors ◽  
2021 ◽  
Author(s):  
Jing Wang ◽  
Alain Wuethrich ◽  
Richard J. Lobb ◽  
Fiach Antaw ◽  
Abu Ali Ibn Sina ◽  
...  
Keyword(s):  
Extracellular Vesicle ◽  
Multiple Cancer ◽  
Cancer Types

scholarly journals Development of Group B Coxsackievirus as an Oncolytic Virus: Opportunities and Challenges

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1082
Author(s):  
Huitao Liu ◽  
Honglin Luo
Keyword(s):  
Tumor Cells ◽  
Current Knowledge ◽  
Oncolytic Viruses ◽  
Human Enterovirus ◽  
Multiple Cancer ◽  
The Family ◽  
Cancer Types ◽  
Group B ◽  
Type 3 ◽  
Genus Enterovirus

Oncolytic viruses have emerged as a promising strategy for cancer therapy due to their dual ability to selectively infect and lyse tumor cells and to induce systemic anti-tumor immunity. Among various candidate viruses, coxsackievirus group B (CVBs) have attracted increasing attention in recent years. CVBs are a group of small, non-enveloped, single-stranded, positive-sense RNA viruses, belonging to species human Enterovirus B in the genus Enterovirus of the family Picornaviridae. Preclinical studies have demonstrated potent anti-tumor activities for CVBs, particularly type 3, against multiple cancer types, including lung, breast, and colorectal cancer. Various approaches have been proposed or applied to enhance the safety and specificity of CVBs towards tumor cells and to further increase their anti-tumor efficacy. This review summarizes current knowledge and strategies for developing CVBs as oncolytic viruses for cancer virotherapy. The challenges arising from these studies and future prospects are also discussed in this review.

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