Continuation of immunotherapy beyond progression is beneficial to the survival of advanced non-small-cell lung cancer.

PURPOSE: To investigate the potential clinical importance of continuing immunotherapy beyond progression in patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: The data of patients with aNSCLC who experienced progressive disease after receiving first-line immunotherapy plus chemotherapy were collected from multiple centers for the period from January 1, 2018 to May 31, 2022. According to the second-line treatment, the patients were classified into two groups: the continuation of immunotherapy beyond progression (CIBP) group and the discontinuation of immunotherapy beyond progression (DIBP) group. The efficacy and safety of the treatment were compared between the groups. RESULTS: Overall, data from 169 patients were analyzed; 93 patients were enrolled in the CIBP group and 76 patients were in the DIBP group. The median second-line progression-free survival was 5.5 months in the CIBP group, which for the DIBP group was 3.4 (p = 0.011). The median overall survival of the CIBP group was 13.3 months, whereas that of the DIBP group was 8.8 months (p = 0.031). The disease control rate of the CIBP group (79.57%) was observably higher than that of the DIBP group (64.47%; p = 0.028). Among patients who responded better (complete or partial response) to prior therapy, the median progression-free survival was 5.5 months and 3.3 months in the CIBP and DIBP groups respectively (p = 0.022), and the median overall survival was 14.8 months and 8.8 months in the CIBP and DIBP groups respectively (p = 0.046). CONCLUSIONS: Continuing immunotherapy as a second-line treatment could be beneficial to the survival of patients with aNSCLC with disease progression beyond initial chemotherapy combined with immunotherapy.

MSCohi-O lenses for long-term retention of mesenchymal stem cells on ocular surface as a therapeutic approach for chronic ocular graft-versus-host disease.

Chronic ocular graft-versus-host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can lead to vision loss if not diagnosed and treated promptly. Currently, no approved drugs exist for oGVHD treatment. However, umbilical cord-derived mesenchymal stem cells (UCMSCs) have known immunoregulatory properties and have been employed in clinical trials for immune-mediated diseases. To address oGVHD, the application of UCMSCs to the ocular surface is a logical approach. Intravenous administration of UCMSCs poses risks, necessitating topical and local delivery. Retaining UCMSCs on the ocular surface remains a challenge. To overcome this, we invented mesenchymal stem cell-coating high oxygen-permeable hydrogel lenses combining UCMSCs and machinery to enable the long-term retention of UCMSCs on the ocular surface. Animal model experiments demonstrated that these lenses effectively retained UCMSCs, providing therapeutic benefits by decreasing corneal inflammation and damage, and inhibiting immune rejection and response, all crucial aspects in oGVHD treatment.

Application of biomaterials and tissue engineering in bladder regeneration.

The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.

Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer.

DNA ligase (LIG) plays a key role in connecting the 3'-OH end of a DNA strand to the 5'-P end of another DNA strand, resulting in the formation of a phosphodiester bond. It has been reported that LIGs (including LIG1, LIG3 and LIG4) play important roles in the occurrence and progression of many cancers. However, the role of LIGs in breast cancer (BC) is still unclear. In this study, we aim to reveal the expression level, function, and prognostic value of LIGs in BC. Bioinformatic tools were used to study the expression level, potential function and prognostic value of LIG1 and LIG3 in BC patients. ENCORI was used to predict microRNAs (miRNAs) that regulate LIG1 and LIG3 and established a valuable miRNA-mRNA regulation network for BC. We found that the expression of LIG1 and LIG3 was upregulated in BC and predicted high relapse-free survival (RFS) in BC patients. Functional annotation analysis was performed to reveal the role of LIG1 and LIG3 in BC. In addition, hsa-miR-22-3p was identified to be potentially involved in the regulation of LIG3. We suggest that LIG1 and LIG3 are novel valuable prognostic biomarkers for BC and has-miRNA-22-3p may be a potential therapeutic target for BC.

The Alterations and Potential Roles of MCMs in Breast Cancer.

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2-8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4-7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4-7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

Epithelial Splicing Regulatory Protein 1 Is Overexpressed in Breast Cancer and Predicts Poor Prognosis for Breast Cancer Patients.

BACKGROUND Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, are important proteins for alternative splicing of mRNAs and are reported to promote or inhibit the progression of some tumors. However, the effects of ESRPs in breast cancer are still unknown. MATERIAL AND METHODS In this study, we detected the transcriptional level and alterations of ESRP1 in patients with breast cancer based on the Oncomine, Gene Expression Profiling Interactive Analysis, Gene Expression-Based Outcome for Breast Cancer Online, and cBioPortal databases. Using immunohistochemistry and quantitative polymerase chain reaction, the expression pattern of ESRP1 in breast cancer was analyzed. Analysis of the clinicopathological characteristics and function of ESRP1 in breast cancer were actualized through the University of Alabama Cancer database and Database for Annotation, Visualization and Integrated Discovery. Using the Kaplan-Meier plotter, the prognostic values of ESRP1 in patients with breast cancer were analyzed. The Encyclopedia of RNA Interactomes database was used to predict miRNAs that regulated ESRP1. RESULTS We found that ESRP1 was significantly overexpressed in patients with breast cancer, compared with patients without breast cancer, and had statistically significant clinicopathological characteristics. Kaplan-Meier plotter analysis indicated that the elevated expression of ESRP1 was associated with poor prognosis in patients with breast cancer. Furthermore, hsa-miR-181c-5p was identified to be potentially involved in the regulation of ESRP1. CONCLUSIONS These results suggest that ESRP1 is a valuable target for the precise treatment of breast cancer and a potential biomarker for the prognosis of patients with breast cancer.

Primitive neuroectodermal tumors: a clinical and radiological analysis of six cases.

BACKGROUND: Primitive neuroectodermal tumor (PNET) is extremely rare and highly aggressive with poor prognosis. Few studies concerning PNET's the imaging features have been published. METHODS: Six cases of PNET, all confirmed by pathology and immunohistochemical (IHC) examinations, were treated during January 2012 to December 2016. These cases' clinical course and imaging findings were retrospectively analyzed. RESULTS: Among six PNET cases, one located in left superior abdomen, one case at posterior abdominal wall, one case in right orbit, one case in left frontal temporal lobe, one case in pelvic cavity, and one case located in left supraclavicular fossa. The tumor's density was uniform for small tumor and heterogeneous for large tumors on CT images, while the size of tumors differed during presentation depending on the location of the tumor. Marked enhancement was visualized after injection of contrast media. The demarcation between the lesion and adjacent tissues or organs tended to be unclear. On magnetic resonance imaging (MRI) images, the mass mainly showed heterogeneously long T1 and long T2 signal intensity, mixed high signal intensity on fluid-attenuated inversion recovery (FLAIR) image. In two cases maximum intensity projection image reconstruction demonstrates tortuous blood vessels within the tumor on enhanced CT images. Five cases were treated by surgical resection with two cases received adjuvant radiotherapy and three cases received adjuvant chemotherapy. Six patients were followed up with a mean period of 34.5 months (ranging from 6 to 55 months). Five patients survived and one died. Among the five patients undergoing surgeries, one patient presented pelvic and abdominal recurrence/metastasis 2 months after abdominal PNET resection. One patient had a recurrent lesion in the right orbit involving the right ethmoid sinus 6 months after right orbital PNET resection. One patient's pelvic tumor recurred 7 months after PNET operation, and this patient died after 1 year and 10 months of follow-up. During the follow-up period, the remaining three cases did not show obvious recurrence and/or metastasis. CONCLUSIONS: Overall, the imaging appearances of PNET lack characteristics. PNETs generally do not have clear boundary, or partially so, with its adjacent organs or tissues suggesting their invasive nature. Upon further validation, maximum intensity projection image reconstruction demonstrates tortuous blood vessels within the tumor on enhanced CT images may be valuable information for the diagnosis of PNET.

Intraviral interactome of Chikungunya virus reveals the homo-oligomerization and palmitoylation of structural protein TF.

Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. Although the protein-protein interactions (PPIs) between nonstructural proteins of CHIKV have been extensively established, the complete CHIKV intraviral interactome remains to be elucidated. In this study, we examined all possible CHIKV intraviral PPIs by immunoprecipitation and constructed the intraviral interactome of CHIKV. We reported 19 novel PPIs including the homo-oligomerization of TF. Disulfide bonds promoted the oligomerization of CHIKV TF protein. 2-BP, a palmitoylation inhibitor reduced the palmitoylation of TF and increased TF oligomerization. A quadruple mutant of Cys33, Cys35, Cys41, and Cys43 in TF blocked its palmitoylation and reduced oligomerization. Furthermore, we determined the association of TF with nsP1 and nsP3 in a palmitoylation-dependent manner. Construction of intraviral interactome of CHIKV provides the basis for further studying the function of CHIKV proteins.

Knockdown the P2X3 receptor in the stellate ganglia of rats relieved the diabetic cardiac autonomic neuropathy.

Diabetic cardiac autonomic neuropathy (DCAN) is a common and serious complication of diabetes mellitus (DM), is manifested by nerve fiber injury in the sympathetic and parasympathetic nerve of the autonomic nervous system, and causes hypertension, cardiac arrhythmias, silent myocardial infarction, and sudden death. Our previous study observed that P2X3 receptor in superior cervical ganglia in rat was associated with sympathetic neuropathy caused by myocardial ischemia. However, whether the P2X3 receptor is involved in the diabetic cardiac autonomic neuropathy and the underlying mechanisms remain unclear. The aim of this research was explored the effect of P2X3 short hairpin RNA (shRNA) on information transmission of sympathetic nerve induced by DCAN. Sprague-Dawley (SD) male rats were randomly divided into four groups: Control, DM, DM treated with P2X3 shRNA and DM treated with scramble shRNA. Blood pressure, heart rate and heart rate variability were measured in each group. The expression of P2X3 in stellate ganglion (SG) was detected by immunohistochemistry, western blotting and QPCR. Results showed that P2X3 shRNA alleviated blood pressure and heart rate, improved heart rate variability, decreased the up-regulated expression levels of P2X3, interleukin-1beta and tumor necrosis factor alpha in stellate ganglion (SG) of diabetic rats. P2X3 shRNA also reduced the incremental concentration of serum epinephrine and the phosphorylation level of extracellular regulated protein kinases1/2 in diabetic rats. These results indicated that P2X3 shRNA could decrease sympathetic activity via inhibiting P2X3 receptor in the SG to alleviate DCAN.