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PurposeCompared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa).MethodsA retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3–4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression.ResultsThe SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P

Breast cancer is the most common malignancy in women, and there is evidence for the dual role of cell pyroptosis in tumor development. However, little is known about the relationship between cell pyroptosis and breast cancer and its prognostic value. We aimed to construct a prognostic model using cell-pyroptosis-related genes to provide innovative insights into the prognosis and treatment of breast cancer. We screened candidate genes for pyroptosis using public databases and identified 10 cell pyroptosis signature genes with the random forest method. Finally, a nomogram for predicting 1-, 3-, and 5-year survival probabilities was constructed. The differences in immune cell distributions between survival periods were similar across the breast cancer datasets. The 10 identified key pyroptosis factors showed a significant correlation with Her2, tumor–node–metastasis (TNM) stage, and survival of breast cancer. The risk scores correlated positively with the infiltration features of naive B cells, CD8+ T cells, atpdelnd mast cells, while they correlated negatively with those of M0 macrophages and dendritic cells. In conclusion, our findings confirm that cell pyroptosis is closely associated with breast cancer. Importantly, the prognostic complex values generated from the 10 cell-pyroptosis-related genes based on various clinical features may provide an important basis for future studies on the prognosis of breast cancer.

BNIP3 is a BH3-only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here, we undertook a quantitative analysis of BNIP3 expression and functions in single-cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer 3D organoid cultures compared with 2D culture. Taken together, the combination of in silico perturbations using public single-cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.

BackgroundApigenin (APG), a natural flavonoid, can affect the development of a variety of tumors, but its role in ovarian cancer remains unclear. There has been an increasing amount of evidence supporting the vital role played by mast cells and the bioactive mediators they release, as components of the tumor microenvironment, in the progression of ovarian cancer (OC); however, the mechanism warrants further exploration.Methods and ResultsIn this study, a combination of transcriptomics analysis and application of TCGA database was performed, and we found that the expression of genes related to mast cell degranulation in ovarian cancer tissues changed remarkably. We then explored whether histamine, a major constituent of mast cell degranulation, could affect the development of ovarian cancer through immunohistochemistry analysis and cell proliferation assays. The results showed that a certain concentration of histamine promoted the proliferation of ovarian cancer cells by upregulating the expression of estrogen receptor α (ERα)/estrogen receptor β (ERβ). Additionally, we found that the inhibition of ERα or the activation of ERβ could inhibit the proliferation of ovarian cancer cells induced by histamine through real-time PCR and western blot assays. Finally, we demonstrated the attenuation effect imparted by apigenin in histamine-mediated ovarian cancer via the PI3K/AKT/mTOR signaling pathway.ConclusionOur research revealed that apigenin decelerated ovarian cancer development by downregulating ER-mediated PI3K/AKT/mTOR expression, thus providing evidence of its applicability as a potentially effective therapeutic agent for ovarian cancer treatment.

Radiotherapy is an essential component of multi-modality treatment of glioblastoma (GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly activated DNA damage response (DDR) mechanisms as a consequence of oncogene overexpression, persistent replicative stress, and other so far unknown reasons. The molecular chaperone heat shock protein 90 (HSP90) plays an important role in the establishment and maintenance of treatment resistance, since it crucially assists the folding and stabilization of various DDR regulators. Accordingly, inhibition of HSP90 represents a multi-target strategy to interfere with DDR function and to sensitize cancer cells to radiotherapy. Using NW457, a pochoxime-based HSP90 inhibitor with favorable brain pharmacokinetic profile, we show here that HSP90 inhibition at low concentrations with per se limited cytotoxicity leads to downregulation of various DNA damage response factors on the protein level, distinct transcriptomic alterations, impaired DNA damage repair, and reduced clonogenic survival in response to ionizing irradiation in glioblastoma cells in vitro. In vivo, HSP90 inhibition by NW457 improved the therapeutic outcome of fractionated CBCT-based irradiation in an orthotopic, syngeneic GBM mouse model, both in terms of tumor progression and survival. Nevertheless, in view of the promising in vitro results the in vivo efficacy was not as strong as expected, although apart from the radiosensitizing effects HSP90 inhibition also reduced irradiation-induced GBM cell migration and tumor invasiveness. Hence, our findings identify the combination of HSP90 inhibition and radiotherapy in principle as a promising strategy for GBM treatment whose performance needs to be further optimized by improved inhibitor substances, better formulations and/or administration routes, and fine-tuned treatment sequences.

Background: FUN14 domain containing 1 (FUNDC1) plays a pivotal role in mitochondrial autophagy (mitophagy), which is closely associated with human immunity. However, the role of FUNDC1 in cancers remains unclear. This study aimed to visualize the prognostic landscape of FUNDC1 in pan-cancer and investigate the relationship between FUNDC1 expression and immune infiltration.Methods: In this study, we explored the expression pattern and prognostic value of FUNDC1 in pan-cancer across multiple databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter. Then, using the GEPIA and TIMER databases, we investigated the correlations between FUNDC1 expression and immune infiltration in cancers, especially liver hepatocellular carcinoma (LIHC), and lung squamous cell carcinoma (LUSC).Results: In general, compared with that in normal tissue, tumor tissue had a higher expression level of FUNDC1. Although FUNDC1 showed a protective effect on pan-cancer, a high expression level of FUNDC1 was detrimental to the survival of LIHC patients. Although different from what was found for LUSC, for LIHC, there were significant positive correlations between FUNDC1 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells. Furthermore, markers of infiltrating immune cells, such as tumor-associated-macrophages (TAMs), exhibited different FUNDC1-related immune infiltration patterns.Conclusion: The mitophagy regulator FUNDC1 can serve as a prognostic biomarker in pan-cancer and is correlated with immune infiltrates.

Purpose: Compared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa). Methods: A retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3-4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression. Results: The SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS =8, and tPSA >20 ng/ml and GS=8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT. Conclusion: 99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies. [ABSTRACT FROM AUTHOR]