Role of cell division cycle-associated proteins in regulating cell cycle and promoting tumor progression.

The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.

Exposure to microcystin-LR promotes the progression of colitis-associated colorectal cancer by inducing barrier disruption and gut microbiota dysbiosis.

Microcystins (MCs) are secondary metabolites generated by cyanobacterial blooms, among which microcystin-LR (MC-LR) stands out as the most widely distributed variant in aquatic environments. However, the effects of MC-LR on the colorectum and its role in promoting colorectal tumor progression remain unclear. Therefore, this study aims to scrutinize the impact of MC-LR on a mice model of colitis-associated colorectal cancer and elucidate the potential underlying molecular mechanisms. In this study, we used AOM/DSS mice and orally administered MC-LR at doses of 40 µg/kg or 200 µg/kg. Exposure to MC-LR increased tumor burden, promoted tumor growth, shortened colon size, and decreased goblet cell numbers and tight junction protein levels in intestinal tissues. Additionally, exposure to MC-LR induced alterations in the structure of gut microbiota in the mouse colon, characterized by an increase in the relative abundance of Escherichia_coli and Shigella_sonnei, and a decline in the relative abundance of Akkermansia_muciniphila. Transcriptomic analysis revealed that MC-LR exposure activated the IL-17 signaling pathway in mouse colorectal tissues and participated in inflammation regulation and immune response. Immunofluorescence results demonstrated an increase in T-helper 17 (Th17) cell levels in mouse colorectal tumors following MC-LR exposure. The results from RT-qPCR revealed that MC-LR induced the upregulation of IL-6, IL-1ß, IL-10, IL-17A, TNF-α, CXCL1, CXCL2, CXCL5 and CCL20. The novelty of this study lies in its comprehensive approach to understanding the mechanisms by which MC-LR may contribute to CRC progression, offering new perspectives and valuable reference points for establishing guidance standards regarding MC-LR in drinking water. Our findings suggest that even at guideline value, MC-LR can have profound effects on susceptible mice, emphasizing the need for a reevaluation of guideline value and a deeper understanding of the role of environmental toxins in cancer progression.

Ablation of Small Liver Metastases Presenting as Foci of Diffusion Restriction on MRI-Results from the Prospective Minimally Invasive Thermal Ablation (MITA) Study.

PURPOSE: Liver metastases presenting as small hyperintense foci on diffusion-weighted imaging (DWI) pose a therapeutic challenge. Ablation is generally not possible since these lesions are often occult on ultrasound and CT. The purpose of this prospective study was to assess if small liver metastases (≤10 mm) detected on DWI can be successfully localized and ablated with the Hepatic Arteriography and C-Arm CT-Guided Ablation technique (HepACAGA). MATERIALS AND METHODS: All consecutive patients with small liver metastases (≤10 mm), as measured on DWI, referred for ablation with HepACAGA between 1 January 2021, and 31 October 2023, were included. Re-ablations and ablations concomitant with another local treatment were excluded. The primary outcome was the technical success rate, defined as the intraprocedural detection and subsequent successful ablation of small liver metastases using HepACAGA. Secondary outcomes included the primary and secondary local tumor progression (LTP) rates and the complication rate. RESULTS: A total of 15 patients (26 tumors) were included, with liver metastases from colorectal cancer (73%), neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). All 26 tumors were successfully identified, punctured and ablated (a technical success rate of 100%). After a median follow-up of 9 months, primary and secondary LTP were 4% and 0%, respectively. No complications occurred. CONCLUSION: In this proof-of-concept study, the HepACAGA technique was successfully used to detect and ablate 100% of small liver metastases identified on DWI with a low recurrence rate and no complications. This technique enables the ablation of subcentimeter liver metastases detected on MRI.

Mitochondrial inhibitors: a new horizon in breast cancer therapy.

Breast cancer, due to resistance to standard therapies such as endocrine therapy, anti-HER2 therapy and chemotherapy, continues to pose a major health challenge. A growing body of research emphasizes the heterogeneity and plasticity of metabolism in breast cancer. Because differences in subtypes exhibit a bias toward metabolic pathways, targeting mitochondrial inhibitors shows great potential as stand-alone or adjuvant cancer therapies. Multiple therapeutic candidates are currently in various stages of preclinical studies and clinical openings. However, specific inhibitors have been shown to face multiple challenges (e.g., single metabolic therapies, mitochondrial structure and enzymes, etc.), and combining with standard therapies or targeting multiple metabolic pathways may be necessary. In this paper, we review the critical role of mitochondrial metabolic functions, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid cycle, and fatty acid and amino acid metabolism, in metabolic reprogramming of breast cancer cells. In addition, we outline the impact of mitochondrial dysfunction on metabolic pathways in different subtypes of breast cancer and mitochondrial inhibitors targeting different metabolic pathways, aiming to provide additional ideas for the development of mitochondrial inhibitors and to improve the efficacy of existing therapies for breast cancer.

Comparative analysis of upfront stereotactic radiosurgery and watchful waiting in the management of newly diagnosed vestibular schwannomas: a systematic review and meta-analysis.

Vestibular schwannomas (VS) are benign intracranial tumors posing significant management challenges. This study aims to compare the outcomes of stereotactic radiosurgery (SRS) and watchful waiting (WW) in the management of newly diagnosed VS, integrating findings from both retrospective and the pioneering V-REX prospective trial. Adhering to PRISMA guidelines, a systematic review was conducted using MEDLINE, Embase, and Cochrane databases. Studies directly comparing SRS with WW for newly diagnosed VS were included. Primary outcomes focused on hearing preservation assessed through the AAO-HNS or Gardner-Robertson hearing classification scales and tumor progression, with secondary outcomes focusing on neurological symptoms, and the need for further treatment. Thirteen studies encompassing 1,635 patients (WW: 891; SRS: 744) were included.While no significant difference was found in serviceable hearing loss at last follow-up (RR = 1.51, [95%CI: 0.98, 2.32], p = 0.06), significant differences favoring WW were observed in pure tone audiometry (PTA) (MD = -13.51 [95%CI: -22.66, -4.37], p = 0.004) and word recognition score (WRS) (MD = 20.48 [95%CI: 9.72, 31.25], p = 0.0002). Analysis of tumor progression indicated no overall significant difference in risk between SRS and WW (RR = 0.40, [95%CI 0.07, 2.40], p = 0.32), but subgroup analysis suggested a lower risk with SRS in certain contexts. The need for further treatments favored SRS (RR = 0.24, [95%CI: 0.07, 0.74], p = 0.007). No significant differences were found in tinnitus and imbalance between the two groups. This comprehensive analysis suggests no marked difference in functional hearing preservation between SRS and WW in managing VS. However, untreated tumors commonly necessitate additional interventions. These findings highlight the need for individualized treatment decisions and underscore the importance of continued monitoring. The study advocates for further prospective trials to refine management strategies for VS.

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Role of the P2X7 receptor in breast cancer progression.

Breast cancer is a common malignant tumor, whose incidence is increasing year by year, and it has become the malignant tumor with the highest incidence rate in women. Purine ligand-gated ion channel 7 receptor (P2X7R) is a cation channel receptor with Adenosine triphosphate ( ATP) as a ligand, which is widely distributed in cells and tissues, and is closely related to tumorigenesis and progression. P2X7R plays an important role in cancer by interacting with ATP. Studies have shown that P2X7R is up-regulated in breast cancer and can promote tumor invasion and metastasis by activating the protein kinase B (AKT) signaling pathway, promoting epithelial-mesenchymal transition (EMT), controlling the generation of extracellular vesicle (EV), and regulating the expression of the inflammatory protein cyclooxygenase 2 (COX-2). Furthermore, P2X7R was proven to play an essential role in the proliferation and apoptosis of breast cancer cells. Recently, inhibitors targeting P2X7R have been found to inhibit the progression of breast cancer. Natural P2X7R antagonists, such as rhodopsin, and the isoquinoline alkaloid berberine, have also been shown to be effective in inhibiting breast cancer progression. In this article, we review the research progress of P2X7R and breast cancer intending to provide new targets and directions for breast cancer treatment.

LncRNA PITPNA-AS1 mediates the diagnostic potential of miR-129-5p in prostate cancer.

BACKGROUND: LncRNA has an effective value in many diseases, which has long been applied in the diagnosis, treatment and prognosis of prostate cancer. This study focused on lncRNA PITPNA-AS1, and its diagnostic potential in prostate cancer has been explored. METHODS: The expression of PITPNA-AS1 and miR-129-5p in prostate cancer serum and sample cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The relationship between the expression of PITPNA-AS1 and clinicopathological parameters was considered. ROC curve prompted the diagnostic value of PITPNA-AS1. The effect of PITPNA-AS1 on prostate cancer cells was verified using vitro cells assay. Luciferase activity assay and RIP assay demonstrated the sponge relationship of PITPNA-AS1 to miR-129-5p. RESULTS: PITPNA-AS1 level was increased, while miR-129-5p was obviously decreased in prostate cancer. PITPNA-AS1 expression was associated with Gleason grade, lymph node metastasis and TNM stage in patients. The area under the curve (AUC) was 0.910, with high sensitivity and specificity. PITPNA-AS1 was elucidated to directly target miR-129-5p, whereas silencing PITPNA-AS1 negatively affected prostate cancer cell proliferation, migration and invasion. Intervention of miR-129-5p inhibitor reversed the effect of silencing PITPNA-AS1 on cells. CONCLUSIONS: PITPNA-AS1 was relatively highly expressed in prostate cancer and mediated the pathophysiological process of patients, which may serve as a diagnostic indicator. Silencing of the PITPNA-AS1 sponge miR-129-5p inhibited the biological function of the cells, indicating that PITPNA-AS1 may represent a novel therapeutic target for prostate cancer.

Reactive astrocytes promote tumor progression by up-regulating tumor protocadherin 1 expression in lung cancer brain metastasis.

Brain metastasis (BM) is one of the main causes of death in patients with non-small cell lung carcinoma. The specific pathological processes of BM, which are inextricably linked to the brain tumor microenvironment, such as the abundance of astrocytes, lead to limited treatment options and poor prognosis. Reactive astrocytes are acquired in the BM; however, the underlying mechanisms remain unclear. This study aimed to explore the mechanisms by which astrocytes promote BM development. We determined the crucial role of reactive astrocytes in promoting the proliferation and migration of brain metastatic lung tumor cells by upregulating protocadherin 1 (PCDH1) expression in an in vitro co-culture model. The overexpression of PCDH1 was confirmed in clinical BM samples using immunohistochemical staining. Survival analysis indicated that high-PCDH1 expression was associated with poor survival in patients with lung adenocarcinoma. In vivo assays further showed that silence of PCDH1 effectively inhibited the tumor progression of brain metastases and prolonged the survival of animals. RNA sequencing has revealed that PCDH1 plays an important role in cell proliferation and adhesion. In conclusion, the present study revealed the promoting role of astrocytes in enhancing the aggressive phenotype of brain metastatic tumor cells by regulating the expression of PCDH1, which might be a biomarker for BM diagnosis and prognosis, suggesting the potential efficacy of targeting important astrocyte-tumor interactions in the treatment of patients with non-small cell lung carcinoma with BM.

Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration.

Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.

Label-Free Monitoring of Endometrial Cancer Progression Using Multiphoton Microscopy.

Endometrial cancer is the most common gynecological cancer in the developed world. However, the accuracy of current diagnostic methods is still unsatisfactory and time-consuming. Here, we presented an alternate approach to monitoring the progression of endometrial cancer via multiphoton microscopy imaging and analysis of collagen, which is often overlooked in current endometrial cancer diagnosis protocols but can offer a crucial signature in cancer biology. Multiphoton microscopy (MPM) based on the second-harmonic generation and two-photon excited fluorescence was introduced to visualize the microenvironment of endometrium in normal, hyperplasia without atypia, atypical hyperplasia, and endometrial cancer specimens. Furthermore, automatic image analysis based on the MPM image processing algorithm was used to quantify the differences in the collagen morphological features among them. MPM enables the visualization of the morphological details and alterations of the glands in the development process of endometrial cancer, including irregular changes in the structure of the gland, increased ratio of the gland to the interstitium, and atypical changes in the glandular epithelial cells. Moreover, the destructed basement membrane caused by gland proliferation and fusion is clearly shown in SHG images, which is a key feature for identifying endometrial cancer progression. Quantitative analysis reveals that the formation of endometrial cancer is accompanied by an increase in collagen fiber length and width, a progressive linearization and loosening of interstitial collagen, and a more random arrangement of interstitial collagen. Observation and quantitative analysis of interstitial collagen provide invaluable information in monitoring the progression of endometrial cancer. Label-free multiphoton imaging reported here has the potential to become an in situ histological tool for effective and accurate early diagnosis and detection of malignant lesions in endometrial cancer.

Comparing long and intermediate-length plates for metastatic bone disease of the proximal humerus: A retrospective analysis.

AIMS: Managing proximal humerus pathologic fractures requires strategic planning to ensure optimal patient outcomes. Traditionally, fixation of the humerus using long devices has been considered the standard of care, but emerging evidence has challenged this approach. This study aimed to compare long plates (LPs) and intermediate-length plates (IPs) in this clinical context. METHODS: Forty-four patients with proximal humerus metastatic bone disease were retrospectively studied from 2013 to 2019, with 11 (25%) receiving long plates (LPs) and 33 (75%) intermediate-length plates (IPs). Outcomes included tumor progression, reoperation rates, postoperative anemia, blood loss, operation time, and hospitalization duration. Tumor progression was classified into three categories, with Type III progression (new metastatic lesions in the distal humerus) theoretically benefiting most from whole bone stabilization. RESULTS: Tumor progression occurred in three patients (7%), all of them was in IPs. No revision surgery was needed to address these tumor progressions, including one type III progression which occurred 34 months postoperatively after IP surgery. IP were associated with a reduced operation time compared with LP (median, 1.5 h [IQR, 1.2-1.9] vs. 2.4 [IQR, 1.7-2.5]; p = 0.004). No differences were found for the other perioperative outcomes. CONCLUSIONS: Our findings reveal a low incidence of tumor progression and low reoperation rates in both groups. The shortened operative time associated with IP use suggests its particular suitability for patients with limited life expectancy. Further research is needed to elucidate the ideal prosthesis length that best balances the risks and benefits when addressing proximal humerus metastatic disease.

Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells.

Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole. There was a decrease in the levels of HIF-1α, G6PDH, GAPDH, PDH, and CS after Mel treatment even in the presence of luzindole in both OC cells. Mel treatment also reduced the activity of OC-related enzymes including PFK-1, G6PDH, LDH, CS, and GS whereas PDH activity was increased. Lactate and glutamine levels dropped after Mel treatment. Mel further promoted a reduction in the concentrations of CREB, JNK, NF-kB, p-38, ERK1/2, AKT, P70S6K, and STAT in both cell lines. Mel reverses Warburg-type metabolism and possibly reduces glutaminolysis, thereby attenuating various oncogenic molecules associated with OC progression and invasion.

TMPRSS2 is a tumor suppressor and its downregulation promotes antitumor immunity and immunotherapy response in lung adenocarcinoma.

BACKGROUND: TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored. METHODS: In five bulk transcriptomics datasets, one single-cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings. RESULTS: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. CONCLUSIONS: TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.

Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in advanced HBV-HCC.

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling.

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

The role of ATP-binding cassette subfamily G member 1 in tumor progression.

BACKGROUND: ATP-binding cassette subfamily G member 1 is mostly known as a transporter for intracellular cholesterol efflux, and a number of studies indicate that ABCG1 also functions actively in tumor initiation and progression. This review aimed to provide an overall review of how ABCG1 acts in tumor progression. METHOD: A comprehensive searching about ABCG1 and tumor was conducted up to November 2023 using proper keywords through databases including PubMed and Web of Science. RESULT: Overall, ABCG1 plays a crucial role in the development of multiple tumorigenesis. ABCG1 enhances tumor-promoting ability through conferring stem-like properties to cancer cells and mediates chemoresistance in multiple cancers. Additionally, ABCG1 may act as a kinase to phosphorylate downstream molecules and induces tumor growth. In tumor microenvironment, ABCG1 plays a substantial role in immunity response through macrophages to create a tumor-favoring circumstance. CONCLUSION: High expression of ABCG1 is usually associated with poor prognosis, which means ABCG1 may be a potential biomarker for early diagnosis and prognosis of various cancers. ABCG1-targeted therapy may provide a novel treatment for cancer patients.

Identifying the Morphological and Molecular Features of a Cell-Based Orthotopic Pancreatic Cancer Mouse Model during Growth over Time.

Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.