Advances in therapeutic cancer vaccines: Harnessing immune adjuvants for enhanced efficacy and future perspectives.

Preventive cancer vaccines are highly effective in preventing viral infection-induced cancer, but advances in therapeutic cancer vaccines with a focus on eliminating cancer cells through immunotherapy are limited. To develop therapeutic cancer vaccines, the integration of optimal adjuvants is a potential strategy to enhance or complement existing therapeutic approaches. However, conventional adjuvants do not satisfy the criteria of clinical trials for therapeutic cancer vaccines. To improve the effects of adjuvants in therapeutic cancer vaccines, effective vaccination strategies must be formulated and novel adjuvants must be identified. This review offers an overview of the current advancements in therapeutic cancer vaccines and highlights in situ vaccination approaches that can be synergistically combined with other immunotherapies by harnessing the adjuvant effects. Additionally, the refinement of adjuvant systems using cutting-edge technologies and the elucidation of molecular mechanisms underlying immunogenic cell death to facilitate the development of innovative adjuvants have been discussed.

CSSLdb: Discovery of cancer-specific synthetic lethal interactions based on machine learning and statistic inference.

Synthetic lethality (SL) occurs when the inactivation of two genes results in cell death while the inactivation of either gene alone is non-lethal. SL-based therapy has become a promising anti-cancer treatment option with the increasing researches and applications in clinical practice, while the specific therapeutic opportunities for various cancers have not yet been comprehensively investigated. Herein, we described a computational approach based on machine learning and statistical inference to discover the cancer-specific synthetic lethal interactions. First, Random Forest and One-Class SVM were used to perform cancer unbiased prediction of synthetic lethality. Then, two strategies, including mutual exclusivity and differential expression, were used to screen cancer-specific synthetic lethal interactions, resulting in 14,582 SL gene pairs in 33 cancer types. Finally, we developed a freely available database of CSSLdb (Cancer Specific Synthetic Lethality Database, http://www.tmliang.cn/CSSL/) to present cancer-specific synthetic lethal genetic interactions, which would enrich the relevant research and contribute to underlying therapy strategies based on synthetic lethality.

Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer.

Autophagy, a complex and highly regulated cellular process, is critical for the maintenance of cellular homeostasis by lysosomal degradation of cellular debris, intracellular pathogens, and dysfunctional organelles. It has become an interesting and attractive topic in cancer because of its dual role as a tumor suppressor and cell survival mechanism. As a highly conserved pathway, autophagy is strictly regulated by diverse non-coding RNAs (ncRNAs), ranging from short and flexible miRNAs to lncRNAs and even circRNAs, which largely contribute to autophagy regulatory networks via complex RNA interactions. The potential roles of RNA interactions during autophagy, especially in cancer procession and further anticancer treatment, will aid our understanding of related RNAs in autophagy in tumorigenesis and cancer treatment. Herein, we mainly summarized autophagy-related mRNAs and ncRNAs, also providing RNA-RNA interactions and their potential roles in cancer prognosis, which may deepen our understanding of the relationships between various RNAs during autophagy and provide new insights into autophagy-related therapeutic strategies in personalized medicine.

Unleashing the Power of Synthetic Lethality: Augmenting Treatment Efficacy through Synergistic Integration with Chemotherapy Drugs.

Cancer is the second leading cause of death in the world, and chemotherapy is one of the main methods of cancer treatment. However, the resistance of cancer cells to chemotherapeutic drugs has always been the main reason affecting the therapeutic effect. Synthetic lethality has emerged as a promising approach to augment the sensitivity of cancer cells to chemotherapy agents. Synthetic lethality (SL) refers to the specific cell death resulting from the simultaneous mutation of two non-lethal genes, which individually allow cell survival. This comprehensive review explores the classification of SL, screening methods, and research advancements in SL inhibitors, including Poly (ADP-ribose) polymerase (PARP) inhibitors, Ataxia telangiectasia and Rad3-related (ATR) inhibitors, WEE1 G2 checkpoint kinase (WEE1) inhibitors, and protein arginine methyltransferase 5 (PRMT5) inhibitors. Emphasizing their combined use with chemotherapy drugs, we aim to unveil more effective treatment strategies for cancer patients.

Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/ß-Catenin Signaling Pathway in Tumor Progression.

Dysregulated expression of specific non-coding RNAs (ncRNAs) has been strongly linked to tumorigenesis, cancer progression, and therapeutic resistance. These ncRNAs can act as either oncogenes or tumor suppressors, thereby serving as valuable diagnostic and prognostic markers. Numerous studies have implicated the participation of ncRNAs in the regulation of diverse signaling pathways, including the pivotal Wnt/ß-catenin signaling pathway that is widely acknowledged for its pivotal role in embryogenesis, cellular proliferation, and tumor biology control. Recent emerging evidence has shed light on the capacity of ncRNAs to interact with key components of the Wnt/ß-catenin signaling pathway, thereby modulating the expression of Wnt target genes in cancer cells. Notably, the activity of this pathway can reciprocally influence the expression levels of ncRNAs. However, comprehensive analysis investigating the specific ncRNAs associated with the Wnt/ß-catenin signaling pathway and their intricate interactions in cancer remains elusive. Based on these noteworthy findings, this review aims to unravel the intricate associations between ncRNAs and the Wnt/ß-catenin signaling pathway during cancer initiation, progression, and their potential implications for therapeutic interventions. Additionally, we provide a comprehensive overview of the characteristics of ncRNAs and the Wnt/ß-catenin signaling pathway, accompanied by a thorough discussion of their functional roles in tumor biology. Targeting ncRNAs and molecules associated with the Wnt/ß-catenin signaling pathway may emerge as a promising and effective therapeutic strategy in future cancer treatments.

Development and validation of a risk prediction model for diabetic retinopathy in type 2 diabetic patients.

To establish a risk prediction model and make individualized assessment for the susceptible diabetic retinopathy (DR) population in type 2 diabetic mellitus (T2DM) patients. According to the retrieval strategy, inclusion and exclusion criteria, the relevant meta-analyses on DR risk factors were searched and evaluated. The pooled odds ratio (OR) or relative risk (RR) of each risk factor was obtained and calculated for ß coefficients using logistic regression (LR) model. Besides, an electronic patient-reported outcome questionnaire was developed and 60 cases of DR and non-DR T2DM patients were investigated to validate the developed model. Receiver operating characteristic curve (ROC) was drawn to verify the prediction accuracy of the model. After retrieving, eight meta-analyses with a total of 15,654 cases and 12 risk factors associated with the onset of DR in T2DM, including weight loss surgery, myopia, lipid-lowing drugs, intensive glucose control, course of T2DM, glycated hemoglobin (HbA1c), fasting plasma glucose, hypertension, gender, insulin treatment, residence, and smoking were included for LR modeling. These factors, followed by the respective ß coefficient was bariatric surgery (- 0.942), myopia (- 0.357), lipid-lowering drug follow-up < 3y (- 0.994), lipid-lowering drug follow-up > 3y (- 0.223), course of T2DM (0.174), HbA1c (0.372), fasting plasma glucose (0.223), insulin therapy (0.688), rural residence (0.199), smoking (- 0.083), hypertension (0.405), male (0.548), intensive glycemic control (- 0.400) with constant term α (- 0.949) in the constructed model. The area under receiver operating characteristic curve (AUC) of the model in the external validation was 0.912. An application was presented as an example of use. In conclusion, the risk prediction model of DR is developed, which makes individualized assessment for the susceptible DR population feasible and needs to be further verified with large sample size application.

[Clinical investigation of different routes of administration of dexamethasone on sudden deafness].

OBJECTIVE: To investigate the therapeutic effects of conventional treatment with different routes of administration of dexamethasone on sudden deafness. METHOD: Eighty-four patients with sudden deafness were included in this prospective randomized study. Twenty one patients (group 1) were treated with taking dexamethasone orally combined with conventional methods. Another 21 patients (group 2) were treated with intravenous dexamethasone injection combined with conventional methods. Group 3 (21 patients) were treated with intratympanic dexamethasone injection by the way of external ear combined with conventional methods. The other 21 patients (group 4) were treated with intratympanic dexamethasone injection by the way of pharyngotympanic tube combined with conventional methods. The hearing gains at 0.5, 1.0, 2.0, 4.0 kHz and the mean values were compared among four groups. RESULTS: The average hearing gains of 1, 2, 3 and 4 group was 21.3 dB, 27.5 dB, 43.2 dB and 48.1 dB respectively. Group 3 and group 4 had statistical difference compared with group 1 and group 2 in the average hearing gains. There was no obviously statistical difference between group 1 and group 2 and between group 3 and group 4. In patients with PTA < or = 70 dB, the average hearing gains at 0.5, 1.0, 2.0, 4.0 kHz had no obvious difference (P > 0.05) among four groups. However, in patients with PTA > 70 dB, there was statistical difference between group 1, 2 and group 3, 4 (P < 0.05), the hearing gains of group 3. 4 were apparently higher than that of group 1, 2. However, there was no significant difference of hearing gains between group 1 and group 2 (P > 0.05) and between group 3 and group 4 (P > 0.05). CONCLUSION: The conventional drug treatment with taking dexamethasone orally or intravenous dexamethasone injection had no obvious effect on sudden deafness with PTA > 70 dB, but the conventional drug treatment with intratympanic dexamethasone injection is a useful treatment for sudden deafness. Comparison with whole body administration, intratympanic dexamethasone injection is more convenient to use in clinic, and with less prohibitions and complications. Patients with PTA > 70 dB should take intratympanic dexamethasone injection in early days.