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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.

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.

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.

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."

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.

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.

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.

Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

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.