Malignant Cancer Cells Research Articles

Genetic Factors and MicroRNAs in the Development of Gallbladder Cancer: The Prospective Clinical Targets.

Gallbladder cancer (GBC) is an uncommon condition in which malignant (cancer) cells are detected in gallbladder tissue. Cancer is often triggered when normal cells turn malignant and begin to spread. Cancer can also be caused by genetic anomalies that result in uncontrolled cell proliferation and tumor development. MicroRNAs (also known as miRNAs or miRs) are a group of small, endogenous, non-coding RNAs of 19-23 nucleotides in length, which play a key role in post-transcriptional gene regulation. These miRNAs serve as negative gene regulators by supervising target genes and regulating biological processes, including cell proliferation, migration, invasion, and apoptosis. Cancer development and progression relate to aberrant miRNA expression. This review demonstrated the implication of various genetic factors and microRNAs in developing and regulating GBC. This suggests the potential of genes and RNAs as the diagnostic, prognostic, and therapeutic targets in gallbladder cancer.

MiR-4319 targets tuftelin 1 to reduce malignancy of cervical cancer cells.

Cervical cancer (CC) is the most common malignant tumor of female reproductive system. MiR-4319 has been identified as an anti-oncogene in various cancers. In the present study, role of miR-4319 in CC was identified. Colony formation, flow cytometer, wound healing, and transwell assays were used to detect CC cell proliferation, apoptosis, migration, and invasion. The expression of miR-4319 was decreased in clinical CC tissues and CC cell lines. Upregulation of miR-4319 suppressed cell viability, proliferation, migration, and invasion, and induced cell apoptosis in CC cells. Moreover, tuftelin 1 (TUFT1) was verified as a direct target of miR-4319, as confirmed by dual-luciferase reporter assay. Additionally, TUFT1 expression was remarkably increased in clinical CC tissues and CC cell lines and was negatively associated with miR-4319 expression. Furthermore, overexpression of TUFT1 partially restored the effects of miR-4319 mimic on cell viability, proliferation, migration, invasion, and cell apoptosis in CC cells. To conclude, miR-4319 played an anti-cancer role in the occurrence and development of CC, which might be achieved by targeting TUFT1.

Abstract 4383: Atypical protein kinases C-ζ and ι-inhibitors impede the growth of malignant gastric cancer cells

Abstract Currently, the global data on gastric cancer demonstrate that it is the fifth most common type of cancer and as far as cancer-related death is concerned, it is the third most common type. The high mortality of gastric cancer can be attributed to the fact that it is mostly diagnosed when the disease has progressed to the advanced stage. While the bacterium Helicobacter pylori is known to be the most common cause of gastric cancer, other notable risk factors also include high salt intake, age and diets lacking in fruits and vegetables. Demographic data have revealed that the regions of East Asia, Eastern Europe and South America are notable hotspots of this type of cancer. Endoscopic resection is considered as the major treatment procedure for early detected gastric cancer while those diagnosed in later stages are treated with surgeries such as D2 lymphadenectomy. Previously, the Atypical Protein Kinases C (aPKCs) - ζ and ι - have been documented to play significant roles in elevated cell proliferation in various cancer types. Here, we employed two inhibitors, ICA-1S (5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide and ζ-stat (8-hydroxy-1,3,6- naphthalenetrisulfonic acid), that specifically inhibit aPKC-ι and-ζ respectively on a gastric cancer cell line (i.e., AGS) to observe their effects on cell proliferation. In separate trials, AGS cells were treated with ICA-1S and ζ-stat for 72 hours (about 3 days). An assortment of drug concentrations for each of the inhibitors were tried and the analysis of the cell count demonstrated that the cell proliferation decreases were statistically significant for both drugs in all concentrations. In case of ICA-1S, the highest decrease in cell proliferation was observed at 20 µM (p < 0.0001), whereas in case of ζ-stat, the highest decrease was observed at 10 µM (p < 0.0001). Our previous research have revealed that these aPKC inhibitors downregulate the aPKCs-ι and-ζ and interfere with established cancer pathways to cause cell deaths. Based on that and the results from the preliminary data on this project, it can be hypothesized that these two aPKC inhibitors have the potential to lead to Gastric Cancer cell deaths, which could potentially open a new door for Gastric Cancer therapeutics. Henceforth, the Western Blot analysis of AGS cells treated with ζ-stat have demonstrated the downregulation of the aPKC-ζ protein. Likewise, a downregulation of the apoptosis-related markers, Survivin and Caspase-3, was also illustrated in ζ-stat treated cells. Current, investigations include how these aPKC inhibitors, ICA-1S and ζ-stat, play into some of the well-established gastric cancer pathways to lead to cell deaths with techniques such as Western Blot analysis, Immunoprecipitation Assays and Flow cytometry. Citation Format: Abiral Hasib Shourav, Mahfuza Marzan, Khandker Mohammad Khalid, Wishrawana Sarathi Ratnayake, Mildred Acevedo-Duncan. Atypical protein kinases C-ζ and ι-inhibitors impede the growth of malignant gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4383.

Abstract 1798: Glyoxalase 1 (GLO1) as an oncometabolic enabler of prostate cancer progression: CRISPR/Cas9-based GLO1-deletion from human DU145-Luc2 cells blocks EMT and bone metastasis in SCID mice

Abstract Glyoxalase 1 (encoded by GLO1) is a glutathione-dependent enzyme detoxifying the glycolytic byproduct methylglyoxal (MG), an oncometabolite involved in metabolic reprogramming. Recently, we have demonstrated that GLO1 is overexpressed in human prostate cancer cells and patient tumors. In order to inform the ongoing debate on the role of GLO1 as an oncometabolic enabler of tumor glucose metabolism and malignant progression, we performed CRISPR/Cas9-based GLO1-deletion in human DU145-Luc2 malignant prostate cancer cells. NanoString nCounterTM ('PanCancer-Progression-Panel') comparative gene expression profiling (GLO1_KO versus GLO1_wt) revealed a significant downregulation of EMT-related pathways in GLO1_KO cells; concordantly, phenotypical screening indicated a pronounced attenuation of matrigel invasiveness observable in GLO1_KO cells. Likewise, inclusion of MG or a small molecule GLO1 inhibitor (TLSC-702) blocked invasiveness of DU145 GLO1_wt cells. Downregulation of EMT-related genes (including MMP3, SPP1, CXCL8) was accompanied by increased expression of TXNIP (thioredoxin-interacting protein), a master regulator of cellular energy metabolism and redox homeostasis. In a bioluminescent SCID mouse bone metastasis model (intracardial injection of DU145-Luc2 GLO1_wt and GLO1_KO cells), GLO1 expression was necessary to cause mandibular bone metastases (as evidenced by the complete absence of bone metastases after GLO1 deletion). Given the availability of drug-like small molecule inhibitors of GLO1 enzymatic activity these data suggest that GLO1 represents a novel molecular target for the pharmacological suppression of prostate cancer bone metastasis. Citation Format: Jana Jandova, Anne E. Cress, Georg T. Wondrak. Glyoxalase 1 (GLO1) as an oncometabolic enabler of prostate cancer progression: CRISPR/Cas9-based GLO1-deletion from human DU145-Luc2 cells blocks EMT and bone metastasis in SCID mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1798.

Abstract 2896: Elucidating the role of transglutaminase 2 (TGM2) in pancreatic ductal adenocarcinoma pathogenesis and its therapeutic implications

Abstract Pancreatic cancer remains one of the deadliest malignancies, with limited therapeutic options and a poor prognosis due to delayed symptom presentation and disease detection. Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 8%, predominantly attributed to oncogenic KRAS mutations and loss-of-function mutations in TP53, SMAD4, and P16. Our lab is interested in studying Transglutaminase 2 (TGM2), a multifunctional enzyme involved in protein cross-linking and cellular signaling, because it is highly correlated with cancer cell survival, malignancy, metastasis, and treatment resistance. Clinically, overexpression of TGM2 is associated with poorer survival in patients with Pancreatic Ductal Adenocarcinoma so it is imperative to understand the mechanism of its action in disease progression. To elucidate the role of TGM2 in PDAC, we studied the targeted deletion of TGM2 in the context of a mouse model of PDAC and saw a significant reduction in PDAC incidence and precursor lesion formation, suggesting that TGM2 has a role in the tumor microenvironment. Using single cell sequencing, we found TGM2 levels to be elevated in certain cell populations, specifically endothelial cells and cancer cells. We discovered high TGM2 levels in TIE2-GFP mouse vessels and subsequently found high TGM2 levels in patient tumor vasculature. Further studies aim to conditionally ablate TGM2 in endothelial cells to assess its mechanistic involvement in PDAC initiation and progression. Additionally, we are studying concurrent conditional TGM2 and SMAD4 deletions in mice to investigate pancreatic cancer precursor lesion formation and are further evaluating the protective mechanisms of a TGM2 deletion in a more aggressive mouse model of PDAC. Our preliminary findings substantiate TGM2 as a critical player in PDAC pathogenesis, opening avenues for targeted therapeutics to ultimately improve patient prognosis. Citation Format: Polina Wright, Azeddine Atfi. Elucidating the role of transglutaminase 2 (TGM2) in pancreatic ductal adenocarcinoma pathogenesis and its therapeutic implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2896.

Abstract 4454: Manipulation of the amino acid metabolism promotes therapeutic efficacy through targeting lysosome in glioblastoma

Abstract Nutrients are converted by the body to smaller molecules, which are utilized for both anabolic and catabolic reactions. Cooperative regulation of these metabolic processes is critical for maintaining tissue homeostasis. Based on these findings, our group has been focusing on how the regulation of nutrient-driven metabolism controls the malignancy of cancer cells. Metabolic regulation has been considered crucial for cellular adaptation to environmental changes and promoting survival and proliferation. Recent studies showed the successful applications of targeting specific nutrients for cancer therapy. In this study, we developed a new lysosome-targeting therapeutic strategy, centered around the manipulation of the amino acid metabolism for GBM. Using patient-derived GBM cells, we found that lysosomal proteolytic activity is a unique metabolic biomarker representing malignant phenotypes of GBM and that it is closely correlated with the efficacy of current conventional therapy for GBM patients. Furthermore, the MiT/TFE family members, TFEB and TFE3, which are the master regulators of lysosomal biogenesis, controlled malignant progression and therapeutic efficacy in vitro and vivo. Combinatory analyses with clinical patient samples and xenograft models demonstrated that the MiT/TFE family plays a crucial role as a regulator of malignant properties in GBM. Analysis of The Cancer Genome Atlas (TCGA) glioma dataset, which includes data from patients with Grade 2, 3, and 4 (GBM) gliomas, showed that higher expression of the MiT/TFE family was significantly associated with shorter survival. Interestingly, we discovered that an essential amino acid controls lysosomal biogenesis and membrane integrity by regulation of nitric oxide signaling pathway. Finally, we screened the potential anti-cancer drugs, including temozolomide, exhibiting the synergy effect in amino acid-restriction conditions by conducting a drug screening using a clinically available anti-cancer drug library. Our study demonstrated that lysosomal function, supported by amino acid metabolism, plays a critical role in the regulation of GBM malignant status and proposed precision nutrition as a promising therapeutic approach. Citation Format: Yongwei Jing, Masahiko Kobayashi, Atsushi Hirao. Manipulation of the amino acid metabolism promotes therapeutic efficacy through targeting lysosome in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4454.

State-of-the-art in transposable element modulation affected by drugs in malignant prostatic cancer cells.

Over recent years, the investigation of transposable elements (TEs) has granted researchers a deeper comprehension of their characteristics and functions, particularly regarding their significance in the mechanisms contributing to cancer development. This manuscript focuses on prostate carcinoma cell lines and offers a comprehensive review intended to scrutinize the associations and interactions between TEs and genes, as well as their response to treatment using various chemical drugs, emphasizing their involvement in cancer progression. We assembled a compendium of articles retrieved from the PubMed database to construct networks demonstrating correlations with genes and pharmaceuticals. In doing so, we linked the transposition of certain TE types to the expression of specific transcripts directly implicated in carcinogenesis. Additionally, we underline that treatment employing different drugs revealed unique patterns of TE reactivation. Our hypothesis gathers the current understanding and guides research toward evidence-based investigations, emphasizing the association between antiviral drugs, chemotherapy, and the reduced expression of TEs in patients affected by prostate cancer.

The Effect of Retinoic Acid on Arsenite-Transformed Malignant UROtsa Bladder Cancer Cells: In Vitro Model of Basal Muscle-Invasive Bladder Cancer.

Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival.

Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer.

The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression.

WW domains form a folded type of nuclear localization signal to guide YAP1 nuclear import.

The nuclear translocation of YAP1 is significantly implicated in the proliferation, stemness, and metastasis of cancer cells. Although the molecular basis underlying YAP1 subcellular distribution has been extensively explored, it remains to be elucidated how the nuclear localization signal guides YAP1 to pass through the nuclear pore complex. Here, we define a globular type of nuclear localization signal composed of folded WW domains, named as WW-NLS. It directs YAP1 nuclear import through the heterodimeric nuclear transport receptors KPNA-KPNB1, bypassing the canonical nuclear localization signal that has been well documented in KPNA/KPNB1-mediated nuclear import. Strikingly, competitive interference with the function of the WW-NLS significantly attenuates YAP1 nuclear translocation and damages stemness gene activation and sphere formation in malignant breast cancer cells. Our findings elucidate a novel globular type of nuclear localization signal to facilitate nuclear entry of WW-containing proteins including YAP1.

Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties

BackgroundRegular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. MethodsExperimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. ResultsLow- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. ConclusionSteady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

247 (PB-063) Poster - SARS-CoV-2 M-protein promotes malignancy of breast cancer cells and alters interaction in breast tumor microenvironment

247 (PB-063) Poster - SARS-CoV-2 M-protein promotes malignancy of breast cancer cells and alters interaction in breast tumor microenvironment

ITGB6 promotes pancreatic fibrosis and aggravates the malignant process of pancreatic cancer via JAK2/STAT3 signaling pathway.

Integrin β6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-β-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment.

Transcription Factor STAT3-Activated LDHB Promotes Tumor Properties of Endometrial Cancer Cells by Inducing MDH2 Expression.

The pathogenesis of endometrial cancer (EC) involves the regulation of lactate dehydrogenases. However, the role and mechanism of lactate dehydrogenase-B (LDHB) in EC progression have not been studied. The mRNA levels of LDHB and malate dehydrogenase 2 (MDH2) were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blotting and immunohistochemistry assays. Cell proliferation, apoptosis, and invasion were analyzed by 5-Ethynyl-2'-deoxyuridine, transwell, and flow cytometry assay, respectively. Glycolysis was investigated using Glucose Assay Kit, CheKine™ Micro Lactate Assay Kit, and ADP/ATP ratio assay kit. An in vivo tumor formation assay was conducted to disclose the effect of LDHB on tumor growth in vivo. The associations among signal transducer and activator of transcription 3 (STAT3), LDHB, and MDH2 were predicted through JASPAR or GeneMANIA online database and identified by chromatin immunoprecipitation assay, dual-luciferase reporter assay, and co-immunoprecipitation assay. LDHB expression was increased in EC tissues and cells in comparison with normal endometrial tissues and human endometrial stromal cells. LDHB had the potential as a biomarker to predict the prognosis of EC patients. In addition, LDHB knockdown inhibited the proliferation, invasion, and glycolysis and promoted apoptosis of RL95-2 and Ishikawa cells. LDHB knockdown inhibited tumor property of Ishikawa cells in vivo. STAT3 bound to the promoter region of LDHB, and STAT3 silencing-induced effects were relieved after LDHB upregulation. LDHB interacted with and regulated MDH2 expression. Moreover, MDH2 overexpression rescued LDHB knockdown-induced effects on EC cell phenotypes. STAT3-activated LDHB promoted endometrial cancer cell malignancy by inducing MDH2 production.

Statement of Retraction: Long noncoding RNA UBA6-AS1 inhibits the malignancy of ovarian cancer cells via suppressing the decay of UBA6 mRNA.

Statement of Retraction: Long noncoding RNA UBA6-AS1 inhibits the malignancy of ovarian cancer cells via suppressing the decay of UBA6 mRNA.

Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures

IntroductionAnti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents.ResultsIn this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as ‘non-mitotic proliferation’ in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog.ConclusionsThe present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies.

ARTICLE REVIEW: UTILIZATION OF CURCUMIN AS AN ANTI-CANCER AGENT

The uncontrolled growth of abnormal cells in one area of the body can spread to other tissues and create more cancer cells, a disease known as cancer. Malignant cancer cells have the potential to become fatal. After cardiovascular disease, cancer is the second most common cause of mortality. Numerous cancer types exist, including stomach, liver, colorectal, lung, breast, and cervical cancers. More than 70% of cancer-related deaths occur in low- and middle-income nations, and the number of cancer-related deaths is predicted to rise steadily, hitting 11.5 million by 2030. Some of the resources utilized to look up information on curcumin's application as an anticancer agent are PubMed, Science Direct, and Google Scholar. Most of the articles that were used were published between 2013 and 2023, or within the last ten years. These journals were found using the following keywords: "Curcumin," "Cancer," "Curcumin as an Anticancer," and "Utilization of Curcumin as an Anticancer Agent." Scholars from many nations have conducted comparable investigations on the application of curcumin as an anticancer agent. Furthermore, it has been established that curcumin directly inhibits cancer cells when used as an anticancer drug. This suggests that curcumin does have anticancer properties. Keywords: Curcumin, Cancer, Curcumin as an Anticancer agent

Analyzing of colorectal cancerrelated genes and microRNAs expression profiles in response to probiotics Lactobacillus acidophilus and Saccharomyces cerevisiae in colon cancer cell lines.

Colorectal cancer is the world's third most frequent cancer and the fourth cause of mortality. Probiotics play an important function in preventing metastasis as well as the growth and proliferation of malignant cancer cells. The study investigated the anticancer effect of Lactobacillus acidophilus supernatant and Saccharomyces cerevisiae yeast on colorectal cell lines, including HT29 and SW480 as a colorectal cancer model. The extract from the Lactobacillus acidophilus and Saccharomyces cerevisiae standard probiotics were prepared, and probiotics characterization was confirmed by morphological and Biochemical tests. The viability of HT29 and SW480 colon cancer cell lines on effecting probiotic supernatant was evaluated by measuring the MTT colorimetric method. Comparison of the expression profile of several genes involved in apoptosis, cell cycle, and metastatic pathway in HT29 and SW480 cell lines with the treatment of probiotics extract showed an upregulation in the BAX, CASP3, and CASP9 and down regulation BCl-2, MMP2, and MMP9 genes. Also, a comparison of microRNA expression profiles indicated an increase of miR 34, 135, 25, 16, 195, 27, 98, let7 and a decrease of miR 9, 106b, 17, 21, 155, 221. The findings of this study indicate that probiotics can effectively suppress the proliferation of colorectal cancer cells and even reverse their development. Additionally, the study of cellular genes and miRNA profiles associated with colorectal cancer have demonstrated that our probiotics play a crucial role in CRC prevention by increasing the expression of tumor suppressor microRNAs and their target genes while decreasing oncogenes.

GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy

As the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC.

Titanium‐Coated Extremely Sensitive SPR Biosensor for Cancer Cell Detection

In this study, a D‐shaped, extremely sensitive surface plasmon resonance (SPR) sensor with a blue shift characteristic is proposed that can be used to identify various malignant cancer cells. A sensing layer made of titanium is inserted to produce intense sensitivity. For the simulation and numerical evaluation of the proposed biosensor, we used the finite element method (FEM) and the COMSOL Multiphysics 5.6 software. To regulate how much light passes through the sensor, which incites the released electrons at the surface of the plasmonic material, air holes in different radii are used. The characteristics that make our proposed sensor superior to other D‐shaped SPR sensors are—it gives an excellent amplitude sensitivity (AS) of 200 RIU−1 also ensures extremely high wavelength sensitivity (WS) spanning from 34,350 to 42,145 nm/RIU with an outstanding spectral resolution of 2.37 × 10−6 RIU. Furthermore, the R2 (0.9966) value is also extremely close to 1 which ensures the quality of our sensor regarding its performance. The given sensor is tailored for four vital human cancers, which are blood cancer, skin cancer, cervical cancer, and adrenal gland cancer. Here, optimization of the structural geometric parameters, plasmonic materials, and material thickness are also conducted in search of the best functionality of the sensor. The offered structure, nonetheless, can be an obvious prologue in the case of the crucial human cancer detection platform due to its mild sensing performances.