#Cancer Cell

Medical News Today

Cancer treatment shows promise against multiple sclerosis in mouse study

About 4% of the world’s population has one of more than 100 autoimmune diseases, such as multiple sclerosis. Most medications used to treat autoimmune diseases suppress a person’s entire immune system, leaving them vulnerable to infections. Researchers from the Washington University School of Medicine in St. Louis discovered...
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Adaptimmune: The Afamicel Rolling BLA Is Its Lifeline

ADAP has been in a sea of trouble, lately. Its rolling BLA of afamicel, to be started this quarter, is its immediate lifeline. Adaptimmune (NASDAQ:ADAP), I noted previously, had been a stagnant stock for long due to a lack of clarity surrounding the BLA submission of its lead asset afami-cel. However, the stock is now up 20% since my last, mainly because of an update from the company that says they will start a rolling BLA this quarter, and complete it by mid-2023. So now we have a date.

Highlighting the molecular mechanism underlying pancreatic cancer development

Researchers have visualized the protein binding site of the (pro)renin receptor known to be involved in pancreatic cancer development using an artificial intelligence-based protein structure prediction program. They predicted the 3D shape of this receptor and revealed the presence of hand-shaped grooves, allowing for the binding of multiple proteins. This...

Structural studies offer 'how-to' guide for designing cancer drugs

To design drugs that stall the growth of aggressive cancers, it helps to know the structures of the proteins that are revving the cancers' engines. In a series of three papers published in Proceedings of the National Academy of Sciences, Scripps Research scientists have illuminated the three-dimensional structure of phosphoinositide 3-kinase alpha (PI3Kα), a protein often mutated in cancer cells. Moreover, the research team shed light on how that structure changes with the cancer-associated mutations, paving the way for drugs that could target only the mutated versions.

Key Regulator of Cell Growth Deciphered

A UNIGE team has discovered the structure of a protein complex that regulates the activity of the major growth regulator. The mTOR protein plays a central role in cell growth, proliferation, and survival. Its activity is affected by the availability of nutrients as well as various growth factors such as hormones. This protein has been linked to a number of diseases, including cancer, where its activity frequently increases.

New cancer treatments may come from disease-killing substances in potatoes and tomatoes

POZNAN, Poland — Potatoes and tomatoes contain compounds that may be useful for developing new cancer drugs, according to new research. Cases of cancer continue to rise worldwide, while progress on finding effective new treatments that don’t cause harmful side-effects has been slow and difficult. However, Polish researchers have found that glycoalkaloids, which are naturally-occurring compounds in commonly consumed vegetables, may have the potential to fight cancer cells.

miR-219-5p attenuates cisplatin resistance of ovarian cancer by inactivating Wnt/β-catenin signaling and autophagy via targeting HMGA2

Our previous study confirmed that miR-219-5p inhibits the progression of ovarian cancer (OC) by targeting high mobility group AT-hook 2 (HMGA2), while the role of miR-219-5p on the chemoresistance of OC is unclear. HMGA2 and miR-219-5p expression in OC tumors and various types of OC cells were determined by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The miRNA profiles in A2780 and cisplatin-resistant A2780 cells were investigated via bulk miRNA sequencing, and the interactions of miR-219-5p and HMGA2 were determined by luciferase reporter activity assay. Cell function was verified through Cell Counting Kit-8, invasion assay, wound-healing, and TUNEL assays. HMGA2 level is highly expressed in cisplatin-resistant OC cell lines compared to normal OC cells, while the expression trend of miR-219-5p is the opposite. In addition, we found that miR-219-5p is one of the miRNAs that have the most significant reduction in levels in the cisplatin-resistant A2780/DDP cell line compared to A2780 cells. Then, we reveal that miR-219-5p directly targets HMGA2 in cisplatin-resistant OC cells, and upregulation of miR-219-5p significantly reduces the resistance of OC cells to cisplatin both in vitro and in vivo. Finally, our results suggest that Wnt/β-catenin signaling and autophagy pathway is involved in the role of miR-219-5p/HMGA2 on resistance of OC cells to cisplatin via gain-of-function experiments. Collectively, the present study shows that miR-219-5p decreases the resistance of OC cells to cisplatin via Wnt/β-catenin signaling and autophagy by regulating HMGA2, which provides a feasible solution for the resistance of OC to chemotherapy.

Which vegetables help reduce cancer?

Health experts believe that the chemicals in potatoes, tomatoes, and eggplants can help to fight cancer. According to Polish researchers, studies have shown that glycoalkaloids (which are naturally present in chili peppers and huckleberries) have some anti-cancer properties. Researchers believe that these active compounds in the vegetable may help patients...

circPLIN2 promotes clear cell renal cell carcinoma progression by binding IGF2BP proteins and miR-199a-3p

Recent evidence has indicated that circular RNAs (circRNAs), a novel type of regulatory RNA, play important roles in the development and progression of various cancers. However, the potential regulatory roles and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) remain largely unclear. Here, we explored circRNA expression profiles in 10 paired samples of RCC (including cancer tissues and surrounding tissues) from the Gene Expression Omnibus (GEO) datasets GSE124453 and GSE108735. We initially identified hsa_circ_0086457, designated circPLIN2, derived from exons 4 to 5 of the PLIN2 gene. We observed that circPLIN2 was preferentially located in the cytoplasm and was more stable than its linear counterpart PLIN2. circPLIN2 was significantly upregulated in ccRCC cells and tissues, and its overexpression was correlated with higher clinical stage and worse prognosis for ccRCC patients. Moreover, gain- and loss-of-function assays indicated that circPLIN2 promoted ccRCC cell proliferation, migration, and invasion in vitro and ccRCC tumor growth and metastasis in vivo. Mechanistically, circPLIN2 not only increased the stability of the c-Myc and MARCKSL1 mRNAs by binding to the KH domains of IGF2BP proteins but also competitively sponged miR-199a-3p to abolish the repressive effect of miR-199a-3p on ZEB1 expression, which ultimately resulted in ccRCC tumorigenesis and progression. Collectively, our results suggest that circPLIN2 may represent a promising diagnostic and prognostic biomarker and a potential therapeutic target for ccRCC patients.

Setting the Stage for ASH 2022

When the 64th American Society of Hematology (ASH) annual meeting kicks off Saturday in New Orleans, established hematology leaders like AstraZeneca, Janssen and Merck will showcase new data, and new players like Vega Therapeutics will launch new programs. Janssen. J&J’s Janssen will take a leading role at this year’s conference...

FAP is critical for ovarian cancer cell survival by sustaining NF-κB activation through recruitment of PRKDC in lipid rafts

Fibroblast activation protein (FAP) is tumor-specific and plays an important role in tumorigenecity. However, agents against its enzymatic activity or extracellular presence were unsuccessful in the clinic for undefined reasons. Here we show that FAP expression is higher in advanced ovarian cancer and is only detected in invasive ovarian cancer cells. Silencing FAP induces apoptosis and FAP's enzymatic activity is dispensable for cell survival. To elucidate the cause of apoptosis, we find that NF-κB activity is diminished when FAP is depleted and BIRC5 (survivin) acts downstream of FAP-NF-κB axis to promote cell survival. To uncover the link between FAP and NF-κB activation, we reveal that PRKDC (DNA-PK, DNA-dependent protein kinase) forms complex with FAP and is required for NF-κB activation and cell survival. Remarkably, FAP-PRKDC interaction occurs only in lipid rafts, and depleting FAP prevents lipid raft localization of PRKDC. Given the known ability of PRKDC to direct NF-κB activation, these results suggest that FAP recruits PRKDC in lipid rafts for NF-κB activation. FAP's non-enzymatic role and functioning from lipid rafts for cell survival also offer an explanation on the failure of past FAP-targeted therapies. Finally, we demonstrate that EpCAM aptamer-delivered FAP siRNA impeded intraperitoneal xenograft development of ovary tumors.

Biology, vulnerabilities and clinical applications of circulating tumour cells

In recent years, exceptional technological advances have enabled the identification and interrogation of rare circulating tumour cells (CTCs) from blood samples of patients, leading to new fields of research and fostering the promise for paradigm-changing, liquid biopsy-based clinical applications. Analysis of CTCs has revealed distinct biological phenotypes, including the presence of CTC clusters and the interaction between CTCs and immune or stromal cells, impacting metastasis formation and providing new insights into cancer vulnerabilities. Here we review the progress made in understanding biological features of CTCs and provide insight into exploiting these developments to design future clinical tools for improving the diagnosis and treatment of cancer.

Exelixis (EXEL) Reports Data from CONTACT-01, QUARTZ-101 Study

EXEL - Free Report) announced that the late-stage CONTACT-01 study failed to achieve its primary endpoint of overall survival at the final analysis. CONTACT-01 is a phase III study evaluating the lead drug Cabometyx (cabozantinib) in combination with Roche’s (. RHHBY - Free Report) Tecentriq (atezolizumab) versus docetaxel in...

Gene amplification-driven lncRNA SNHG6 promotes tumorigenesis via epigenetically suppressing p27 expression and regulating cell cycle in non"“small cell lung cancer

Long non-coding RNAs (lncRNAs) have been validated to play essential roles in non-small cell lung carcinoma (NSCLC) progression. In this study, through systematically screening GSE33532 and GSE29249 from Gene Expression Omnibus (GEO) database and bioinformatics analysis, we found the significant upregulation of SNHG6 in NSCLC. The activation of SNHG6 was driven by copy number amplification and high expression of SNHG6 indicated a poor prognosis. Functionally, the knockdown of SNHG6 inhibited NSCLC cell proliferation, migration, and suppressed the G1/S transition of the cell cycle. SNHG6 overexpression had the opposite effects. Mechanically, SNHG6 recruited EZH2 to the promoter region of p27 and increased H3K27me3 enrichment, thus epigenetically repressing the expression of p27, regulating the cell cycle, and promoting tumorigenesis of NSCLC. SNHG6 silencing restrained tumor growth in vivo and suppressed the expressions of cell cycle-related proteins in the G1/S transition. In conclusion, our study uncovered a novel mechanism of SNHG6 activation and its function. SNHG6 can be considered a potential target for the diagnosis and treatment of NSCLC in the future.

Pals1 functions in redundancy with SMAP1 to inhibit Arf6 in order to prevent Rac1-dependent colorectal cancer cell migration and invasion

Downregulation of cell"“cell adhesion and increased motility are prerequisites for the metastasis of cancer cells. We have recently shown that downregulation of the tight junction adapter protein Pals1 in colorectal cancer cells results in an increase of cell migration, invasion, and metastasis due to the enhanced activation of Arf6 and Rac1. We now reveal a redundancy between the Arf6-GAP SMAP1 and Pals1 in regulating Arf6 activity and thereby Rac1-dependent cell migration. The gene encoding SMAP1 is frequently disrupted in microsatellite instable colorectal cancer specimen and cell lines. In cells expressing SMAP1, deletion of Pals1 leads to disturbed formation of tight junctions but has no impact on Arf6 activity and cell migration. In contrast, inactivation of both SMAP1 and Pals1 results in enhanced Arf6/Rac1 activity and increased cell migration and invasion. Furthermore, analyzing patient cohorts, we found a significant decrease in patient's survival when both genes were downregulated, in contrast to cases, when expression of only one of both genes was affected. Taken together, we identified a redundancy between SMAP1 and Pals1 in the regulation of activation of Arf6/Rac1, thereby controlling cell migration, invasion, and metastasis of colorectal cancer cells.

Glioblastoma glycolytic signature predicts unfavorable prognosis, immunological heterogeneity, and ENO1 promotes microglia M2 polarization and cancer cell malignancy

Glioblastomas are the most malignant brain tumors, whose progress was promoted by aberrate aerobic glycolysis. The immune environment was highly engaged in glioblastoma formation, while its interaction with aerobic glycolysis remained unclear. Herein, we build a 7-gene Glycolytic Score (GS) by Elastic Net in the training set and two independent validating sets. The GS predicted malignant features and poor survival with good performances. Immune functional analyses and Cibersort calculation identified depressed T cells, B cells, natural killer cells immunity, and high immunosuppressive cell infiltration in the high-GS group. Also, high expressions of the immune-escape genes were discovered. Subsequently, the single-cell analyses validated the glycolysis-related immunosuppression. The functional results manifested the high-GS neoplastic cells' association with T cells, NK cells, and macrophage function regulation. The intercellular cross-talk showed strong associations between high-GS neoplastic cells and M2 macrophages/microglia in several immunological pathways. We finally confirmed that ENO1, the key gene of the GS, promoted M2 microglia polarization and glioblastoma cell malignant behaviors via immunofluorescence, clone formation, CCK8, and transwell rescue experiments. These results indicated the interactions between cancerous glycolysis and immunosuppression and glycolysis' role in promoting glioblastoma progression. Conclusively, we built a robust model and discovered strong interaction between GS and immune, shedding light on prognosis management improvement and therapeutic strategies development for glioblastoma patients.

Helping Families Handle Cancer Bereavement Boxes Support Grieving Families and Local Small Businesses

CALGARY, AB / ACCESSWIRE / December 9, 2022 / The loss of a child is an unthinkable pain that no parent should have to experience. At Helping Families Handle Cancer we are aiming to further support the families we cared for during their child's treatment, by collaborating with Avery's Legacy to support families who are experiencing loss. On Saturday, December 10, 2022, we will be assembling 75 beautiful and intentionally curated Bereavement Boxes to gift AT NO COST to parents navigating the journey through the loss of their child to cancer.