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BACKGROUND AND OBJECTIVE: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). METHODS: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0. KEY FINDINGS AND LIMITATIONS: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs. CONCLUSIONS: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC. PATIENT SUMMARY: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.
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BACKGROUND: Bladder cancer (BCa) is a highly prevalent disease with a poor prognosis. There is no better forecasting method for it yet. Current studies demonstrate that pyroptosis is involved in the development and progression of various cancers. METHODS: This study employed bioinformatics techniques to analyze the data of BCa patients obtained from the TCGA and GEO databases in order to construct a prognostic risk model. The TCGA dataset was used for the training set, and the multiple external datasets (including GSE13507, GSE31684, GSE48075, IMvigor210, and GSE32894) were applied as the validation sets. Prognostic-associated pyroptosis genes screened by univariate Cox regression analysis were utilized to construct the lasso Cox regression model. GO and KEGG analysis results identified the selected genes that are primarily involved in the inflammation and cell death processes. The related patients were grouped into low- and high-risk groups. Kaplan-Meier survival analysis was performed to compare survival differences between the risk groups. The accuracy of this risk prediction model was assessed by ROC. We also applied the Human Protein Atlas (HPA) to detect the protein expression of these genes. Subsequently, qRT-PCR was performed to verify the expression of these model genes. RESULTS: There are 29 pyroptosis-related genes with significant expression differences between BCa and corresponding adjacent tissues, and 11 genes (SH2D2A, CHMP4C, MRFAP1L1, GBP2, EHBP1, RAD9A, ANXA1, TMEM109, HEYL, APOL2, ORMDL1) were picked by univariate and LASSO Cox regression analysis. Immunological cell infiltration and ssGSEA results further indicated that the low and high-risk groups were substantially correlated with the immune status of BCa patients. According to TCGA and multiple external datasets, Kaplan-Meier survival curves showed the overall survival rate of the high-risk group to be decreased. ROC curves showed the model established to be accurate and reliable. Moreover, the HPA database also demonstrated the verification of the modeled genes' expression in BCa and normal bladder tissue using the HPA database. qRT-PCR results also suggested the up-regulated EHBP1 and down-regulated RAD9A mRNA expression levels to be confirmed in 15 pairs of BCa and corresponding adjacent tissues. CONCLUSION: This study presents the development and validation of a novel gene signature associated with pyroptosis, which holds the potential for predicting patient outcomes in BCa and providing insights into the immune microenvironment of BCa.
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[This corrects the article DOI: 10.1016/j.heliyon.2023.e16897.].
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A temperature measurement subsystem (TMS) is a critical piece of infrastructure of the space gravitational wave detection platform, necessary for monitoring minuscule temperature changes at the level of 1µK/Hz1/2 within the electrode house, in the frequency range of 0.1mHz to 1Hz. The voltage reference (VR), a key component of the TMS, must possess low noise characteristics in the detection band to minimize the impact on temperature measurements. However, the noise characteristics of the voltage reference in the sub-millihertz range have not been documented yet and require further study. This paper reports a dual-channel measurement method for measuring the low-frequency noise of VR chips down to 0.1mHz. The measurement method makes use of a dual-channel chopper amplifier and an assembly thermal insulation box to achieve a normalized resolution of 3×10-7/Hz1/2@0.1mHz in the VR noise measurement. The seven best-performance VR chips documented at a common frequency range are tested. The results show that their noise at sub-millihertz frequencies can significantly differ from that around 1Hz.
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Background: Transient receptor potential cation channel subfamily V (TRPV) play an essential in cancer initiation, progression, and treatment. TRPV expression alteration are shown relate to multiple cancers prognosis and treatment of cancers but are less-studied in pan-cancer. In this study, we characterize the clinical prediction value of TRPV at pan-cancer level. Methods: Several databases were used to examine the transcript expression difference in tumor vs. normal tissue, copy-number variant (CNV) and single nucleotide polymorphisms (SNP) mutation of each TRPV members in pan-cancer, including The Cancer Genome Atlas (TCGA) and cBioPortal. We performed K-M survival curve and univariate Cox regression analyses to identify survival and prognosis value of TRPV. CellMiner were selected to explore drug sensitivity. We also analyzed association between tumor mutation burden (TMB), microsatellite instability (MSI), tumor immune microenvironment and TRPV family genes expression. Moreover, we investigated the relationship between TRPVs expression and effectiveness of immunotherapy in multiple cohorts, including one melanoma (GSE78220), one renal cell carcinoma (GSE67501), and three bladder cancer cohorts (GSE111636, IMvigor210, GSE176307 and our own sequencing dataset (TRUCE-01)), and further analyzed the changes of TRPVs expression before and after treatment (tislelizumab combined with nab-paclitaxel) of bladder cancer. Next, we made a special effort to investigate and study biological functions of TRPV in bladder cancer using gene set enrichment analysis (GSEA), and conducted immune infiltration analysis with TRPVs family genes expression, copy number or somatic mutations of bladder cancer by TIMER 2.0. Finally, real-time PCR and protein expression validation of TRPVs within 10 paired cancer and para-carcinoma tissue samples, were also performed in bladder cancer. Results: Only TRPV2 expression was lower in most cancer types among TRPV family genes. All TRPVs were correlated with survival changes. Amplification was the significant gene alternation in all TRPVs. Next, analysis between TRPVs and clinical traits showed that TRPVs were related to pathologic stage, TNM stage and first course treatment outcome. Moreover, TRPV expression was highly correlated with MSI and TMB. Immunotherapy is a research hotspot at present, our result showed the significant association between TRPVs expression and immune infiltration indicated that TRPV expression alternation could be used to guide prognosis. In addition, we also discovered that the expression level of TRPV1/2/3/4/6 was positively or negatively correlated with objective responses to anti-PD-1/PD-L1 across multiple immunotherapy cohort. Further analysis of drug sensitivity showed the value to treatment. Based on the above analysis, we next focused on TRPV family in bladder cancer. The result demonstrated TRPV also played an important role in bladder cancer. Finally, qPCR assay verified our analysis in bladder cancer. Conclusion: Our study firstly revealed expression and genome alternation of TRPV in pan-cancer. TRPV could be used to predict prognosis or instructing treatment of human cancers, especially bladder cancer.
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Studying high-sensitivity fiber-optic temperature sensors is vital in pursuing high-precision temperature measurement. We propose a liquid-sealed multimode interference fiber temperature sensor with a double-taper structure. The influence of structure and sealed-liquid material on the temperature sensitivity of the sensor is analyzed experimentally. The results show that the tapered structure can effectively improve the temperature sensitivity of the sensor, and the effect becomes more evident with the increased refractive index of the sealed liquid. As the refractive index of the sealed liquid increases, the temperature sensitivity of the sensor can be effectively improved. However, the sealed liquid with a high refractive index will increase the failure temperature of the sensor. Near the failure temperature, the sensor achieves an ultra-high-temperature sensitivity of -8.28nm/K. The results also prove that further increasing the refractive index of the sealed liquid no longer has a significant gain in temperature sensitivity. It is expected that the relevant research will contribute to the development of high-precision temperature-sensing systems.
