Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia. A retrospective analysis was conducted on pediatric CNS tumors from January 1, 2000, to December 31, 2020, at the Department of Pediatric Oncology and Hematology at the National Institute of Children's Diseases in Bratislava, Slovakia. Among 397 patients (242 males, 155 females), the most common histological types were astrocytomas (42.8%), followed by embryonal tumors (18.4%), brain stem tumors (10.3%), and ependymal tumors (8.1%). Tumor locations were supratentorial (48.1%), infratentorial (46.9%), and spinal (4.3%). Surgical interventions included radical excision (30.2%), subtotal/partial excision (41.8%), and biopsy (9.3%). Treatment modalities varied, with 31.2% receiving combined surgery, chemotherapy, and radiotherapy; 27.5% surgery alone; 9.6% surgery with radiotherapy; 7.8% chemotherapy only; and 6.3% having no treatment. By 2020, 74.3% of patients were alive, with a 25.7% mortality rate. This study outlines the characteristics of pediatric CNS tumors in Bratislava, highlighting the need for multidisciplinary national and international collaboration to advance diagnosis and treatment. Our data align with global findings from other centers.

Esophageal squamous cell carcinoma (ESCC) has high mortality. The role and regulatory mechanism of hsa_circ_0021727 (circ_0021727) in ESCC remain largely unknown. This study focused on the undiscovered impact of circ_0021727 on cell cycle progression, apoptosis, and angiogenesis of ESCC. We found that circ_0021727 levels were significantly upregulated in ESCC cells. TUNEL, flow cytometry, and tubule formation assay indicated that knockdown of circ_0021727 in ESCC induced cell arrest at the G0/G1 phase, promoted apoptosis, and inhibited angiogenesis, whereas overexpression of circ_0021727 produced the opposite effect. Gastrulation brain homeobox 2 (GBX2) GBX2 was a downstream target gene of circ_0021727, and overexpression of GBX2 reversed the effect of circ_0021727 knockdown in ESCC progression. The results of the RIP and RNA pull-down showed that circ_0021727 and GBX2 mRNA bound with eukaryotic translation initiation factor 4A3 (EIF4A3). Overexpression of circ_0021727 promoted GBX2 mRNA stability by binding with EIF4A3. In a tumor xenograft model, the knockdown of circ_0021727 inhibited tumor growth, which was reversed by further overexpression of GBX2. In conclusion, circ_0021727 increased GBX2 mRNA stability by recruiting EIF4A3, which promoted cell cycle progression and angiogenesis in ESCC.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast malignancy. Although some patients benefit from immune checkpoint therapy, current treatment methods rely mainly on chemotherapy. It is imperative to develop predictors of efficacy and identify individuals who will be sensitive to particular treatment regimens. This study analyzed peripheral interferons and immune cell subsets in TNBC patients receiving pre-operative neoadjuvant therapy. The effects of interferon-induced helicase 1 (IFIH1) on the biological characteristics of apoptosis and PD-L1 expression of cancer cells and its potential mechanism were investigated using bioinformatics analysis, clinical specimens, and in vitro study. We found that serum interferon-γ and interferon-α2 levels were significantly higher in TNBC patients with pathologic complete response (pCR). The expression of IFIH1 is markedly upregulated in various tumors, including breast cancer. Immunohistochemical results revealed that IFIH1 was specifically located in the cytoplasm of cancer cells. Gene set enrichment analysis showed that genes co-expressed with IFIH1 were involved in tumor immune-related pathways and apoptosis. Knockdown of IFIH1 in MDA-MB-231 and BT-549 cells resulted in significantly increased cell proliferation and colony formation. Regarding apoptosis-related pathway proteins, there was a significant decrease in levels of phosphorylated TANK-binding kinase 1 (TBK1) and phosphorylated interferon regulatory factor 3 (IRF3). In addition, the expression of PD-L1 was significantly downregulated. Furthermore, we demonstrated the existence of binding sites between IRF3 and PD-L1 promotors. Our data indicate that cancer cell IFIH1 promotes apoptosis and PD-L1 expression, suggesting its potential as a predictive marker of efficacy and therapeutic target in TNBC.

Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance. The results showed decreased resistance after inhibiting PI3K activity. Furthermore, the reduced resistance due to flotillin knockdown was restored after adding the PI3K activator. Additional results showed no changes in PI3K molecules. However, p-AKT expression was downregulated. Further results suggested that the phosphatidylinositol (3,4,5)-trisphosphate/phosphatidylinositol 4,5-bisphosphate (PIP3/PIP2) ratio was downregulated, whereas the phosphatase and tensin homolog (PTEN) expression was upregulated. In addition, we also found that P-gp activity inhibition resulted in increased adriamycin accumulation and reversal of resistance, and flotillin knockdown was accompanied by a downregulation of P-gp expression in CRC cells. In conclusion, our study demonstrated that flotillin knockdown could reverse drug resistance in CRC cells by downregulating the PTEN/PI3K/AKT pathway and P-gp.

MTHFD2 is highly overexpressed in breast cancer tissues, indicating that it might be used as a target in breast cancer treatment. This study aims to determine the role of MTHFD2 in breast cancer cell proliferation and the molecular pathways involved. In order to investigate MTHFD2 gene expression and its downstream pathways in breast cancer, we started our inquiry with a bioinformatics analysis. We then engineered breast cancer cell lines with either silenced or overexpressed MTHFD2 to study its effects on the cell cycle, proliferation, and the m6A methylation status of the gene IFRD1, predicted as a downstream target. Overexpression of MTHFD2 enhanced cellular proliferation, increased the proportion of EdU-positive cells, and accelerated progression into the S+G2/M phase. In contrast, MTHFD2 knockdown led to opposite effects. MTHFD2 and IFRD1 expression levels showed a strong positive association. Increased MTHFD2 activity boosted HDAC3 and mTOR phosphorylation, activating p70 S6K and 4EBP1-key regulators of cell proliferation. Moreover, overexpression of MTHFD2 was associated with reduced p53 acetylation and total protein levels. Silencing MTHFD2 decreased m6A methylation of IFRD1 RNA, whereas its overexpression increased methylation. Notably, IFRD1 siRNA transfection reversed the proliferative effects induced by MTHFD2 overexpression. Furthermore, MTHFD2 knockdown enhanced the sensitivity of breast cancer cells to several chemotherapeutic agents. In conclusion, MTHFD2 influences breast cancer cell proliferation by modulating the m6A methylation of IFRD1 RNA, which regulates the HDAC3/p53/mTOR pathway. These findings suggest that MTHFD2 inhibitors may synergistically enhance the efficacy of existing chemotherapies.

DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC. Seventy-five studies were reviewed, focusing on the promoter methylation of key genes, such as APC, BRCA1, CDH1, CDH13, DAPK1, DLEC1, FHIT, GSTP1, hMLH1, MGMT, CDKN2A, RARβ, RASSF1, RUNX3, and TIMP3. These studies explored diagnostic, prognostic, epidemiological, and therapeutic aspects across NSCLC subtypes. Additionally, mutational profiles of TP53, RB1, KEAP1, and STK11 and expression patterns of ASCL1, DLL3, and NOTCH were analyzed. The findings suggest that LCNEC may serve as a biological bridge between non-small cell and small-cell lung carcinoma. Our analysis highlights that the methylation status of selected genes could enhance diagnosis, prognosis, and personalized treatment strategies in patients with NSCLC, particularly those with LCNEC.

The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.008). In the univariate Cox proportional hazard model, the hazard ratio was 1.653 in pts with present PC (p=0.026) and 1.851 in pts with higher cytoplasmic β-catenin (25-75%) (p=0.009). Multivariate testing of the whole group of 218 pts with NSCLC showed that the presence of PC was associated with a worse prognosis (p=0.018). In the subgroup of 125 pts with adenocarcinoma, OS was significantly improved in pts with higher membranous β-catenin expression (≥50%) than in pts with lower expression (<50%) (p=0.0300) and OS was significantly inferior in pts with higher cytoplasmic β-catenin expression (25-75%) than in pts with lower expression (<25%) (p=0.0004). Multivariate testing of the subgroup of pts with adenocarcinoma showed that cytoplasmic β-catenin (p<0.001) and pleural invasion (p=0.017) were associated with worse prognosis. The present results indicate a negative prognostic significance of PC and cytoplasmic β-catenin expression in NSCLC and a negative prognostic significance of cytoplasmic β-catenin expression in adenocarcinoma.

Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanisms of circ_0075829 on ferroptosis and immune escape in colon cancer. We utilized colon cancer cell lines and a xenograft mouse model to analyze the function of circ_0075829 in vitro and in vivo. The gene expression level was assessed by qRT-PCR and western blotting. Cell proliferation was evaluated using the CCK-8 assay. The targeting relationships between circ_0075829, miR-330-5p, and TCF4 were analyzed through a dual-luciferase reporter experiment and RNA pull-down experiment. Cytokine levels were measured using the ELISA assay. Fe2+, MDA, and SOD levels were tested using appropriate kits, and the ROS level was detected by immunofluorescence. Knockdown of circ_0075829 resulted in increased levels of Fe2+, ROS, and MDA and decreased levels of GPX4 and xCT proteins in cells. Furthermore, silencing of circ_0075829 increased the cell proliferation rates of CD8+T cells co-cultured with colon cells. Moreover, it also enhanced IFN-γ, IL-2, and TNF-α concentration in the supernatants of the co-culturing system and reduced PD-L1 protein expression levels. Subsequently, silencing of circ_0075829 induced ferroptosis and inhibited immune escape in vivo. Meaningfully, we certified that circ_0075829 functions as a sponge for miR-330-5p, leading to the upregulation of TCF4 expression. TCF4 was identified as a downstream target of miR-330-5p. Additionally, co-transfection with anti-miR-330-5p or TCF4 overexpression plasmid reversed the effects observed following the knockout of circ_0075829. Collectively, our research indicates that the circ_0075829 plays a significant role in regulating ferroptosis and immune escape in colon cancer by sponging miR-330-5p to modulate TCF4 expression.

The incidence and mortality trends of lung cancer in Slovakia are not favorable. In our single-center, non-interventional retrospective cohort study, we provide comprehensive information about Slovakia's non-small cell lung cancer (NSCLC) patient population. We evaluated how the introduction of immunotherapy agents affected the survival of NSCLC patients and tried to identify whether the PD-L1 expression level was associated with a negative patient survival effect. The demographics, results of histological and immunohistochemical (PD-L1) examinations, and information about treatment (immunotherapy or standard of care (SOC)) were recorded. In males, squamous cell carcinomas occurred more often than adenocarcinomas (54.40% and 45.08%, respectively), in females, adenocarcinomas clearly dominated (71.88% vs. 27.08%, respectively). The overall proportion of adenocarcinomas was 53.98%. NSCLC patients with stage III and IV treated with SOC treatment (n=54) showed significantly worse overall survival than patients with immunotherapy (n=9) (p=0.026). The comparison of immunotherapy-treated (n=7) and SOC-treated (n=32) adenocarcinoma patients stage III and IV showed similar results (p=0.046). The negative effect of PD-L1 expression level on survival of females with NSCLC and females with adenocarcinoma was visible already at the TPS level of 20-25%. In males with NSCLC, the negative effect was visible at a TPS level of 70-90%. Our results confirm the positive impact of immunotherapy in real-world conditions and show different effects of PD-L1 expression level on patients' survival depending on sex and histology. Determination of different PD-L1 expression breaking points in males and females with NSCLC is a solid starting point for more research on this topic.

Gastric cancer is a globally common type of cancer with a dismal prognosis. Circle RNA_ 0001860 (circ_0001860) is dysregulated in several cancers and involved in cancer development. Its involvement in stomach cancer, however, remains unclear. AGS and HGC-27 cells were transfected with shRNA against circ_0001860 to knock down the circ_0001860 level. The function of circ_0001860 in gastric cancer was analyzed by cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell, ELISA, dual-luciferase reporter, RIP, RNA pull-down, and western blotting. Nude mice were subcutaneously inoculated with AGS cells with lentivirus-packaged sh-circ_0001860 to determine the role of sh-circ_0001860 in gastric cancer by immunohistochemistry assays. circ_0001860 was upregulated in gastric cancer, indicating a poor prognosis for gastric cancer patients. Knockdown of circ_0001860 reduced gastric cancer cells' viability, the percentage of EdU-positive cells, the numbers of invaded cells, and concentrations of IL-10 and TGF-β while fostering the concentrations of IFN-γ and IL-2. circ_0001860 sponged miR-618 to positively modulate the HMGA2 level in gastric cancer cells. The inhibitory role of sh-circ_0001860 on cell growth, invasion, and immune evasion of gastric cancer was abolished with the miR-618 knockdown or the HMGA2 overexpression. Besides, EIF4A3 positively modulated the circ_0001860 level in gastric cancer cells. In vivo, silencing of circ_0001860 reduced tumor size and weight and the expression of HMGA2 and IL-10 but enhanced the level of miR-618 and IFN-γ. Collectively, circle RNA_ 0001860 was induced by EIF4A3 to enhance proliferation, invasion, and immune evasion of gastric cancer through the miR-618/HMGA2 axis.

This study focuses on exploring the role of Six2 in the progression of hepatocellular carcinoma (HCC) and its resistance to the chemotherapy drug 5-fluorouracil (5-FU). Using Hep3B and Huh7 cell lines, we analyzed how Six2 affects various cellular functions, including viability, proliferation, apoptosis, and invasion. Our research also delved into Six2's regulatory impact on DNMT1 levels, E-cadherin expression, and the methylation of the E-cadherin promoter, all of which are crucial for 5-FU resistance in HCC cells. Additionally, we examined the effects of Six2 knockdown on the PI3K/AKT/mTOR signaling pathway. Our findings indicate that overexpression of Six2 enhances cell viability and proliferation, encourages invasive behavior, increases methylation at the E-cadherin promoter, and reduces apoptosis. These changes correspond with increased levels of DNMT1 and decreased levels of E-cadherin, culminating in heightened resistance to 5-FU. Conversely, knocking down Six2 increases the sensitivity of HCC cells to 5-FU and reduces activation of the PI3K/AKT/mTOR pathway. These results suggest that Six2 plays a significant role in promoting HCC proliferation, invasion, and chemotherapy resistance, particularly through mechanisms involving DNMT1 and the PI3K/AKT/mTOR pathway, highlighting its potential as a target for HCC treatment.

The aberrant activation of the hepatocyte growth factor receptor (c-Met) in malignant melanoma is associated with poor prognosis, fostering tumor progression, angiogenesis, and invasiveness. While therapeutic targeting of this pathway has shown promise in several tumors, our previous findings revealed increased tumorigenicity following tyrosine kinase inhibitor SU11274 treatment. Therefore, we hypothesized that administering c-Met inhibitors may elicit distinct effects in human melanoma cells. In this study, we investigated the influence of three c-Met inhibitors, SU11274, crizotinib, and PHA665752, on molecular characteristics, tumorigenicity, and metastatic behavior in three human melanoma cell lines, M4Beu, EGFP-A375 and its metastatic variant, EGFP-A375/Rel3 (Rel3). Crizotinib and PHA665752 induced upregulation of MET proto-oncogene, receptor tyrosine kinase (MET), alongside cancer stem cell marker Prominin 1 (CD133), pluripotency marker Nanog homeobox (Nanog), and genes encoding angiogenic factors and receptors in Rel3 cells, correlating with supportive effect on tumorigenicity in vivo. The increased tumorigenicity of the Rel3 cells following the SU11274 treatment correlated with the elevated phosphorylation of Akt, p70 S6 and RSK kinases. Our results demonstrate pleiotropic changes induced by small-molecule inhibitors of receptor tyrosine kinases in melanoma cell lines.

Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in males, and there are currently few effective therapeutic targets following hormone therapy resistance. Subunits of eukaryotic initiation factor 3 (eIF3) have been implicated in the progression of various cancers. This study aims to investigate the biological functions of the eIF3m subunit in PCa and assess its potential as a novel therapeutic target for treatment. We utilized open-access datasets and patient tissues to analyze the expression and prognostic value of eIF3m in PCa. To explore the role of eIF3m in PCa growth, we established eIF3m knockdown models in PC3 and 22Rv1 cells for both in vitro and in vivo studies. Gene set enrichment analysis (GSEA) was utilized to identify signaling pathways regulated by eIF3m in PCa. Additionally, western blotting and immunochemistry were used to confirm the regulation of c-Myc signaling by eIF3m in PCa. Our results indicated that eIF3m expression was elevated in PCa tissues, with higher levels correlating with an increased risk of biochemical recurrence following radical prostatectomy. Both in vitro and in vivo experiments demonstrated that inhibiting eIF3m significantly impeded the growth of PCa cells. GSEA and immunochemistry further revealed that high eIF3m expression contributed to the activation of c-Myc signaling in PCa patients. Notably, the downregulation of eIF3m resulted in a significant decrease in the expression of c-Myc mRNA and protein in PCa cells. Overall, our findings suggest that eIF3m inhibition significantly suppressed PCa cell growth and c-Myc signaling, indicating that eIF3m is a promising therapeutic target for PCa patients.

Carcinoma of unknown primary (CUP) is defined as a metastatic carcinoma whose primary site cannot be determined, and the absence of a known primary tumor in CUP poses a significant challenge in treatment planning. The purpose of this study was to investigate the protein level of epithelial membrane proteins (EMP) 1, EMP 2, and EMP 3 in CUP and explore their clinical implications. Tissue microarrays were constructed using samples from 72 CUP cases. The histologic subtypes were adenocarcinoma (ADC) in 22% of cases, poorly differentiated carcinoma (PDC) in 15%, squamous cell carcinoma (SCC) in 19%, and undifferentiated carcinoma (UDC) in 14%. Clinically, 17 cases (23.6%) were of favorable type, and 55 cases (76.4%) were of unfavorable type. Immunohistochemical staining for EMP 1, EMP 2, and EMP 3 was performed on the tissue microarrays to investigate the correlation between staining results and clinicopathologic parameters. The investigation of EMP 1, EMP 2, and EMP 3 protein levels in CUP revealed that EMP 2 H-score was significantly higher (p=0.013) in the favorable type, and there was a higher proportion of stromal EMP 1-positivity (p=0.034) and high protein level of tumoral EMP 3 (p=0.002). A positive correlation was observed between EMP 1 and EMP 3 (r=0.425 and p<0.001). In conclusion, CUP exhibits EMP 1, EMP 2, and EMP 3 protein levels, and their protein levels are different according to the clinical subtype.

Effective treatment strategies for second-line therapy in extensive-stage small cell lung cancer (ES-SCLC) are currently lacking. For this reason, we collected and recorded efficacy and safety data from patients with ES-SCLC who had disease progression after first-line treatment and received albumin-bound paclitaxel, anlotinib, and immunotherapy. Preliminary data showed an objective response rate of 37.78%. Median progression-free survival and overall survival were 5 months and 10 months, respectively. Treatment-related adverse events were mostly tolerable. Subgroup analysis indicated that efficacy correlated with the interval from last chemotherapy to treatment initiation and specific drug-related adverse events. Further analysis of immune cell subtypes suggested that the mechanism may involve depletion of immune suppression to activate immune responses synergistically against tumors. With its promising efficacy and manageable adverse effects, this regimen holds potential as a significant option for second-line therapy in ES-SCLC. However, due to the limited sample size, further clinical validation is needed to ascertain its true clinical value.

MYC-rearranged high-grade B-cell lymphoma (HGBCL) patients with concurrent BCL2 rearrangements (HGBCL-MYC/BCL2) often have a poor prognosis with standard chemoimmunotherapy and may benefit from more intensified regimens. Conventional fluorescence in situ hybridization (FISH) is the gold standard for detecting rearrangements, but it has several limitations. This study compared DNA- and RNA-sequencing with FISH to detect clinically relevant rearrangements in HGBCL. Archived formalin-fixed, paraffin-embedded samples from 34 patients who underwent FISH testing were analyzed using targeted DNA- and RNA-sequencing. DNA- and RNA-sequencing identified six and five out of the 12 MYC rearrangements detected by FISH, 10 and 6 out of 10 FISH-detectable BCL2 rearrangements, and 13 and 10 out of the 18 FISH-detectable BCL6 rearrangements. When combining DNA- and RNA-sequencing (integrated NGS), the sensitivity for detecting MYC, BCL2, and BCL6 rearrangements was 58.3%, 100%, and 73.7%, respectively. Both DNA- and RNA-sequencing detected the EIF4A2::BCL6 fusion missed by FISH. FISH identified 12 HGBCL-MYC/BCL2 out of 34 cases, while the integrated NGS strategy identified 7 cases, with 5 cases showing discordant results (41.7%). Additionally, patients with DLBCL/HGBCL-MYC/BCL2 had significantly shorter overall survival than other patients. Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

Due to the delayed delivery of the request for a correction and the requirement from the Office of Zhejiang Chinese Medical University to standardize the institution's English translation, the editorial department of NEOPLASMA has issued a correction in response to the author's signed request: The affiliation of the first author has been changed from "Graduate School of Zhejiang University of Traditional Chinese Medicine" to "Graduate School, Zhejiang Chinese Medical University."

The purpose of this study is to detect the vitamin D (VitD) levels in patients with renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC) using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology to assess the VitD status in subjects using different methods, to understand the true level of VitD in RCC, BC, and PC patients. A total of 170 subjects were included in this study, and their serum VitD metabolite levels were measured, including 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [C3-epi-25(OH)D3, C3-epi], and calculations for 25(OH)D, 25(OH)D2/25(OH)D3, and C3-epi/25(OH)D3 were made. The variations in serum VitD, calcium (Ca), inorganic phosphorus (IP), vitamin D receptor (VDR), and renal function indicators were measured, and their correlations were analyzed. The levels of 25(OH)D, 25(OH)D3, C3-epi, C3-epi /25(OH)D3, and free 25(OH)D [ F25(OH)D] in RCC, BC, and PC patients were significantly lower than that in the healthy control (HC) group (all p<0.05). The ratio of 25(OH)D2/25(OH)D3 was significantly higher in these groups compared to the HC group (all p<0.05). 25(OH)D3 distinguished the HC group from common cancers of the urinary system (including RCC, BC, and PC) in male patients and showed good diagnostic performance. The level of 25(OH)D3 in all three groups was positively correlated with F25(OH)D levels, and in the disease groups, C3-epi levels were positively correlated with both 25(OH)D3 and F25(OH)D levels. This study found that RCC, BC, and PC patients had lower serum levels of 25(OH)D3, C3-epi, and F25(OH)D compared to healthy individuals, with most RCC, BC, and PC patients displaying VitD deficiency.

Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g., cancer. Vitamin D is involved in the regulation of cell proliferation, differentiation, energetic metabolism, and different types of cell death (e.g., apoptosis, autophagy, etc.). In physiological conditions, it is also able to modulate immune responses, angiogenesis, etc., which belongs to fundamental cancer-related processes. Vitamin D deficiency has been associated with an increased risk of some types of cancer, e.g., colorectal, breast, ovarian, prostate, pancreatic, etc. The role of vitamin D in cancer prevention, carcinogenesis, and cancer treatment is still under investigation and depends on the type of cancer. This review summarizes the role of vitamin D in all three above-mentioned aspects and discusses the mechanism of action and potential possibilities in cancer treatment.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

N6-methyladenosine (m6A) methylation, as a new regulatory mechanism, has been reported to be involved in diverse biological processes in recent years. Wilms tumor 1-associated protein (WTAP), as the key member of m6A methylation, has been proven to participate in tumorigenesis. Here, we studied the expression of WTAP and its potential mechanism involved in the development of esophageal squamous cell carcinoma (ESCC). We detected the expression of WTAP and its correlation with clinicopathological features, and we determined the function of WTAP on ESCC cells by MTS assay, colony formation, scratch wound healing assay, Transwell assay, and subcutaneous xenograft assay. We used mRNA sequencing technology to screen candidate downstream targets for WTAP and investigated the underlying mechanism of CCND1 in ESCC promotion through a series of rescue assays. An elevated expression of WTAP in ESCC malignancy indicated a worse prognosis. WTAP promoted the proliferation and metastasis of ESCC cells, and CCND1 was identified as the potential downstream effecter of WTAP. Moreover, WTAP modulated ESCC progression through a MAPK pathway-dependent pattern. Our research suggested that WTAP promoted both proliferation and metastasis of ESCC by accelerating the expression of CCND1 via the MAPK signaling pathway, indicating that WTAP may be a candidate prognostic biomarker for ESCC and also will be a promising strategy for ESCC cancer therapy.