Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment ...strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin-proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy. Keywords: Ubiquitin-specific proteases (USPs), Cancer, Immunotherapy, USP inhibitors
Emerging data have supported the immunostimulatory role of radiotherapy, which could exert a synergistic effect with immune checkpoint inhibitors (ICIs). With proven effective but suboptimal effect ...of ICI and chemotherapy in triple-negative breast cancer (TNBC), we designed a pilot study to explore the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) plus adebrelimab and chemotherapy in TNBC patients.
Treatment-naïve TNBC patients received two cycles of intravenous adebrelimab (20 mg/kg, every 3 weeks), and SBRT (24 Gy/3 f, every other day) started at the second cycle, then followed by six cycles of adebrelimab plus nab-paclitaxel (125 mg/m² on days 1 and 8) and carboplatin (area under the curve 6 mg/mL per min on day 1) every 3 weeks. The surgery was performed within 3-5 weeks after the end of neoadjuvant therapy. Primary endpoint was pathological complete response (pCR, ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), residual cancer burden (RCB) 0-I, and safety.
13 patients were enrolled and received at least one dose of therapy. 10 (76.9%) patients completed SBRT and were included in efficacy analysis. 90% (9/10) of patients achieved pCR, both RCB 0-I and ORR reached 100% with three patients achieved complete remission. Adverse events (AEs) of all-grade and grade 3-4 occurred in 92.3% and 53.8%, respectively. One (7.7%) patient had treatment-related serious AEs. No radiation-related dermatitis or death occurred.
Adding SBRT to adebrelimab and neoadjuvant chemotherapy led to a substantial proportion of pCR with acceptable toxicities, supporting further exploration of this combination in TNBC patients.
None.
NCT05132790.
CMTM6 has been connected to the development of several malignancies. However, it is still unknown what function CMTM6 serves in pancreatic adenocarcinoma (PAAD). We obtained RNA sequencing ...information of PAAD from public datasets and predicted statistical significance of CMTM6 survival in accordance with Kaplan–Meier curves. Gene set enrichment assessment (GSEA) was employed to analyze changes in pathways. Then, we systematically investigated the association involving CMTM6 and the immunological traits within the tumor microenvironment (TME) of PAAD, including immune pathways, immunomodulators, immune infiltrating cells, inflammatory activities, and immunotherapy response prediction. To demonstrate the biologically malignant properties of CMTM6 expression, the Cell Counting Kit-8, transwell experiments, colony formation, and wound healing were utilized. Upregulated CMTM6 expression was revealed within PAAD tissues, which was associated with more frequent somatic mutations and worse survival outcomes. Specifically, CMTM6 expression represented stronger immune infiltration, inflammatory activity, and better immunotherapeutic response in TME. Functional studies revealed that CMTM6 promoted the ability to proliferate, migrate, and invade. Additionally, CMTM6 and PD-L1 had a positive relationship, and CMTM6 can co-immunocoprecipitate with PD-L1 protein in pancreatic cell lines. CMTM6 overexpression shapes the inflammatory TME with a strong immune response. These findings support that CMTM6 is an immunotherapeutic target with promising effect to treat PAAD.
Background
We analyzed the clinical and imaging characteristics of patients with breast ductal carcinoma in situ with microinvasion (DCISM) and breast ductal carcinoma in situ (DCIS).
Methods
We ...analyzed the records of 40 patients diagnosed with DCISM and 61 patients with DCIS who were hospitalized at Shengjing Hospital (Shenyang, China) from January 2009 to June 2016. The size, hardness, and degree of calcification of tumors were determined by mammography and ultrasonography.
Results
In all, 37 DCISM patients and 45 DCIS patients showed clinical palpable masses (92.5% vs 73.77%, P = 0.018). Mammography showed that the mean size of tumor was larger in DCISM patients than that of DCIS patients (3.13 ± 1.51 vs 2.68 ± 1.77, P = 0.030). Ultrasound examination revealed calcification shadows in the solid tumor mass in 17 DCISM cases and 11 DCIS patients (42.5 vs 18.03%, P = 0.007). Furthermore, estrogen receptor positivity and progesterone receptor positivity were more common in DCIS patients (32.5% vs 54.10%, P = 0.033; 22.5% vs 45.90%, P = 0.017), and the percentage of menopausal patients were higher in DCISM patients than that of DCIS patients (70.00% vs 47.54%, P = 0.026).
Conclusion
Clinically palpable and calcified tumor masses on sonography are more commonly encountered in DCISM lesions.
Integrin-linked kinase (ILK), an intracellular serine-threonine kinase, has been reported to be overexpressed in multiple types of human malignancies, including colorectal cancer (CRC). The ...prognostic value of ILK in CRC, however, remains unknown. In the present study, expression of ILK in 25 paired primary CRC samples and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. ILK protein expression was analyzed in 102 archived, paraffin-embedded CRC samples using immunohistochemistry. The correlation between ILK expression and clinicopathological factors was evaluated by the χ
2
test. Patients’ overall survival was analyzed by Kaplan–Meier method. We found that both ILK mRNA and protein expression levels were significantly up-regulated in primary CRC samples compared with their corresponding normal tissues. Immunohistochemical analysis revealed relative high expression of ILK in 43 of 102 (42.2 %) primary CRC samples. Statistical analysis showed a significant correlation of ILK expression with tumor differentiation, lymph node metastasis, tumor invasion, and tumor-node-metastasis stage. Patients with tumors displaying high-level ILK expression showed significantly shorter overall survival (
P
= 0.028, log-rank test). More importantly, multivariate analysis indicated that high ILK protein expression was an independent prognostic factor for CRC patients (
P
= 0.026). Taken together, our data suggest that ILK overexpression is associated with tumor progression and a poor prognosis in CRC patients and may represent a novel potential prognostic marker for patients with CRC.
OBJECTIVE： To explore the effect of electroacu- puncture and Chinese kidney-nourishing medicine on insulin （INS）, adiponectin （APN）, leptin （LEP）, and glucolipid metabolism of obese patients with ...polycystic ovary syndrome （PCOS）. METHODS： Sixty-seven obese PCOS patients were randomly divided into two groups. Thirty-three pa- tients in the acupuncture-medicine group were treated three times a week with electroacupunc- ture at the Tianshu （ST 25）, Zhongwan （CV 2）, Qi- hai （CV 6）, Sanyinjiao （SP 6）, Geshu （BL 17）, and Cil-iao （BL 32） acupoints. They drug, Tiankui capsule, for 3 treatment. Point-taking and also took the Chinese months as a course of treatment in the elec- troacupuncture group of 34 patients was the same as those in the acupuncture-medicine group. We observed and compared the changes in the obesi- ty-related indexes of body weight （BW）, body mass index （BMI）, and waist-hip ratio （WHR）, as well as fasting plasma glucose （FPG）, fasting insulin （FINS）, APN, and LER RESULTS： BW, BMI, WHR, and FINS decreased and insulin sensitivity index （ISI） and APN were higher in the acupuncture-medicine group than in the electroacupuncture group （P〈0.01）. There was no obvious difference in LEP between the two groups （P〉0.05）. CONCLUSION： Acupuncture combined with medi- cine is better than just electroacupuncture for obese PCOS patients by improving obesity-related indexes, insulin sensitivity, and APN level. This indi- cates that acupuncture-medicine therapy is worth clinical popularization.
Chronic pain affects the life quality of the suffering patients and posts heavy problems to the health care system. Conventional medications are usually insufficient for chronic pain management and ...oftentimes results in many adverse effects. The NLRP3 inflammasome controls the processing of proinflammatory cytokine interleukin 1β (IL-1β) and is implicated in a variety of disease conditions. Recently, growing number of evidence suggests that NLRP3 inflammasome is dysregulated under chronic pain condition and contributes to pathogenesis of chronic pain. This review provides an up-to-date summary of the recent findings of the involvement of NLRP3 inflammasome in chronic pain and discussed the expression and regulation of NLRP3 inflammasome-related signaling components in chronic pain conditions. This review also summarized the successful therapeutic approaches that target against NLRP3 inflammasome for chronic pain treatment.
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