Therapeutic cancer vaccines: advancements, challenges, and prospects.

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

Cancer-associated fibroblasts nurture LGR5 marked liver tumor-initiating cells and promote their tumor formation, growth, and metastasis.

BACKGROUND & AIMS: In liver cancer, leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) compartment represents an important tumor-initiating cell (TIC) population and served as a potential therapeutic target. Cancer-associated fibroblasts (CAFs) is a critical part of the tumor microenvironment, heavily influenced TIC function and fate. However, deeply investigations have been hindered by the lack of accurate preclinical models to investigate the interaction between CAFs and TIC. Organoids model have achieved major advancements as a precious research model for recapitulating the morphological aspects of organs, and thus also serving as a candidate model to investigate the mutual interaction between different cell types. Consequently, this study aimed to construct a three-dimensional (3D) co-culture organoid model of primary LGR5-expressing tumor stem cells from primary murine liver tumors with CAFs to investigate the impact of CAFs on LGR5 marked TICs in liver cancer. MATERIALS AND METHODS: First, both of the transgenic LGR5-diphtheria toxin receptor (DTR)-GFP knock-in mice and transgenic Rosa26-mT mice developed primary liver tumors by diethylnitrosamine (DEN) administration. Tumor organoids and CAFs were generated from those primary liver cancer separately. Second, LGR5-expressing TICs organoid with CAFs were established ex vivo based on cell-cell contact or trans-well co-culture system, and the mutual influence between those two types of cells was further investigated. Subsequently, immunodeficient mouse-based xenograft model was further adopted to evaluate the influence of CAFs to LGR5 tumor stem cell, tumor formation, and metastasis. RESULTS: The co-culture organoid model composed of murine liver tumor LGR5+ tumor-initiating cells and CAFs in 3D co-culture was successfully established, with the intention to investigate their mutual interaction. The existence of CAFs upon engrafting tumor organoids resulted in dramatic higher number of LGR5+ cells in the neoplasia when compared with engrafting tumor organoids alone. Furthermore, ex vivo culture of isolated LGR5+ cells from tumors of co-engrafted mice formed significantly larger size of organoids than mono-engrafted. Our results also indicated significantly larger size and number of formed organoids, when LGR5+ cells co-cultured with CAF in both cell-cell contact and paracrine signaling in vitro, comparing to LGR5+ cells alone. Furthermore, we found that specific knockout of LGR5 expressing cells suppressed CAF-mediated promotion of tumor formation, growth, and metastasis in the experimental mice model. CONCLUSIONS: Altogether, in a 3D co-culture type of murine liver LGR5+ cells and cancer-associated fibroblasts, we have demonstrated robust effects of CAFs in the promotion of LGR5 marked liver TICs. We also further revealed the influence of tumor microenvironment on stem cell-related therapy, suggesting the possibility of combing CAF-targeted and tumor stem cell targeted therapy in treating liver cancer.

Legumain: a biomarker for diagnosis and prognosis of human ovarian cancer.

Legumain is a member of the asparaginyl endopeptidase family that is over-expressed in response to hypoxic stress on mammary adenocarcinoma, colorectal cancer, proliferating endothelial cells, and tumor-associated macrophages (TAMs). Here, we demonstrate that elevated expression of legumain in ovarian cancer by a proteomic approach using isobaric tags for relative and absolute quantification (iTRAQ) followed by liquid chromatography-mass spectrometry (LC-MS/MS). To investigate the relationship between legumain expression and ovarian cancer development, we tested legumain expression in malignant human ovarian tumors (n = 60), borderline ovarian tumors (n = 20), benign ovarian tumors (n = 20), and normal ovary samples (n = 20) using immunohistochemical assay (IHC). A correlation between legumain expression, and clinocopathologic and biological variables was also established. Importantly, increased legumain expression was validated by real-time PCR and Western blots, correlated positively with an increased malignancy of ovarian tumors (P < 0.01). In fact, patients with strong legumain expression had a worse prognosis (P = 0.03). In addition, results of in vitro experiments revealed that over-expression of legumain correlates with increased cell migration and invasion of ovarian cancer cells. Although legumain's functional role and clinical utility remain to be established, our results indicated that a sensitive assay for early expression of legumain may serve as both a potential biomarker and a molecular target for treatment of ovarian cancer.

Career Development and Occupational Disease in Chinese Nurses: A Cross-Sectional Study.

BACKGROUND: A high tendency of intention to leave has been noted for nurses in China. The nursing profession is currently unstable. METHODS: A sample of 51406 nurses from 311 hospitals in China who completed the self-administered questionnaire online was recruited via the China Nursing Association by email and phone using a simple random sampling method. The recruitment occurred between July 2016 and July 2017. RESULTS: The majority of the nurses had working experience ≤20 years and had to work on night shifts. A high percentage of nurses (71.8%) had insomnia, followed by 37.0% who developed varicose veins and 40.9% who experienced musculoskeletal-related disorders. The proportions of the nurses who developed gastrointestinal and urinary system diseases were 56.0% and 18.2%, respectively. Nearly half of the nurses did not have a clear goal for their future career development and intended to leave. Nurses with long working hours each week were positively associated with the development of occupational diseases. The prevalence of occupational diseases was independently associated with career development. CONCLUSIONS: A high prevalence of occupational diseases was noted among nurses in China. The data indicated that 50% of the nurses were vague regarding their career planning. The data suggest that managers need to pay more attention and to prevent this problem. Appropriate interventions should also be provided.

Designing a Needs-Oriented Psychological Intervention for Chinese Women Undergoing an Abortion.

Accessing good quality abortion care is a fundamental human right and contributes to achieving Sustainable Development Goals. However, well-designed abortion care that meets women's needs is limited. This study aims to systematically develop an intervention to promote the psychological well-being of Chinese women undergoing an abortion. A five-step iterative approach informed by intervention mapping was undertaken to determine the intervention design. Step 1 used in-depth interviews with 14 Chinese women undergoing an abortion to assess real-life stressors and support needs. We identified eight stressors and found women's support needs varied with the time trajectory of the abortion. Step 2 used a focus group discussion with care providers to select modifiable stressors that impact negative psychological outcomes. In Step 3 and Step 4, we determined and integrated the exact strategies to eliminate or mitigate possible modifiable stressors by incorporating information from in-depth interviews and the Transactional Model of Stress and Coping. The integrated strategies were instructional support, informational support, and timely communication. In Step 5, we composed the detailed intervention design according to the best available evidence and, to confirm content validity, consulted 10 women who had undergone abortion in the previous 2-6 weeks. The intervention was titled STress-And-coping suppoRT (START), which included four interacting components: (1) a face-to-face consultation at the first appointment; (2) a printed booklet with information on abortion, self-care, and managing emotions and intimate relationships; (3) a WeChat-based online public profile page offering the same information as the booklet; (4) a telephone hotline. This study paves the way for a new approach to addressing the psychological needs of women experiencing abortion in China. The rigorous process provides an example of developing tailored health promotion interventions.