A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity.

Rationale: Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis. Methods: We devise a hierarchically unlocking nanoSTING stimulant liposome (AUG) as a neoadjuvant chemoimmunotherapy agent in the debulking of tumors prior to surgery and prevention of postoperative tumor recurrence and metastasis by simultaneously activating innate and adaptive antitumor immune responses. In the weakly acidic tumor microenvironment, the hydrazone bond within AUG is initially cleaved, leading to the release of a cyclic seven-membered ring containing tertiary amine that serve to activate the stimulator of interferon genes (STING) pathway. Following this, AUG undergoes degradation within lysosomes, facilitating the release of doxorubicin and ultimately inducing immunogenic cell death along with leakage of double-stranded DNA into the cytoplasm. Results: The hierarchically acidity-unlocking pattern enables cascaded STING activation, achieving over 90% tumor growth inhibition in subcutaneous xenograft model and preventing 75% of mice from postsurgical metastasis or recurrence when combined with immune checkpoint inhibitors. Conclusion: Our strategy highlights the potency of AUG as a neoadjuvant paradigm for presurgical tumor debulking and as a preventive measure against postoperative tumor recurrence and metastasis.

Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-Stimulation Engineering Scaffold for Potent Immunotherapy.

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.

Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold.

In situ vaccine (ISV) is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire. However, its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity. To break this plight, a tumor-activated and optically reinforced immunoscaffold (TURN) is exploited to trigger cancer immunoediting phases regression, thus levering potent systemic antitumor immune responses. Upon response to tumoral reactive oxygen species, TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines, and thus immunosuppression falls and immunogenicity rises. Subsequently, intermittent laser irradiation-activated photothermal agents (PL) trigger abundant tumor antigens exposure, which causes immunogenicity springs and preliminary infiltration of T cells. Finally, CD137 agonists from TURN further promotes the proliferation, function, and survival of T cells for durable antitumor effects. Therefore, cancer immunoediting phases reverse and systemic antitumor immune responses occur. TURN achieves over 90 % tumor growth inhibition in both primary and secondary tumor lesions, induces potent systemic immune responses, and triggers superior long-term immune memory in vivo. Taken together, TURN provides a prospective sight for ISV from the perspective of immunoediting phases.

Hierarchical-unlocking virus-esque NanoCRISPR precisely disrupts autocrine and paracrine pathway of VEGF for tumor inhibition and antiangiogenesis.

Vascular endothelial growth factor (VEGF) not only serves as an autocrine survival factor for tumor cells themselves, but also stimulates angiogenesis by paracrine pathway. Strategies targeting VEGF holds tremendous potential for tumor therapy, however, agents targeting VEGF are limited by intolerable side effects, together with incomplete and temporary blocking of VEGF, resulting in unsatisfactory and unsustained therapeutic outcomes. Herein, hierarchical-unlocking virus-esque NanoCRISPR (HUNGER) is constructed for complete, permanent and efficient intracellular disruption of autocrine and paracrine pathway of VEGF, thereby eliciting notable tumor inhibition and antiangiogenesis. After intravenous administration, HUNGER exhibits prolonged blood circulation and hyaluronic acid-CD44 mediated tumor-targeting capability. Subsequently, when matrix metalloproteinase-2 is overexpressed in the tumor microenvironment, the PEG layer will be removed. The cell-penetrating peptide R8 endows HUNGER deep tumor penetration and specific cellular uptake. Upon cellular internalization, HUNGER undergoes hyaluronidase-triggered deshielding in lysosome, lysosomal escape is realized swiftly, and then the loaded CRISPR/Cas9 plasmid (>8 kb) is transported to nucleus efficiently. Consequentially, complete, permanent and efficient intracellular disruption of autocrine and paracrine pathway of VEGF ensures inhibition of angiogenesis and tumor growth with inappreciable toxicity. Overall, this work opens a brand-new avenue for anti-VEGF therapy and presents a feasible strategy for in vivo delivery of CRISPR/Cas9 system.

A programmable releasing versatile hydrogel platform boosts systemic immune responses via sculpting tumor immunogenicity and reversing tolerogenic dendritic cells.

Immunogenicity improvement is a valuable strategy for tumor immunotherapy. However, immunosuppressive factors bestow tolerogenic phenotype on tumor-infiltrating DCs, which exhibit weak antigen presentation and strong anti-inflammatory cytokines secretion abilities, limiting the effectiveness of tumor immunotherapy even if the tumor has adequate immunogenicity. Herein, we designed a programmable releasing versatile hydrogel platform (PIVOT) to sculpt tumor immunogenicity, increase intratumoral DCs and cDC1s abundance, and reverse the tolerogenic phenotype of DCs, thus promoting their maturation for boosting innate and adaptive immune responses. Responsive to tumoral reactive oxygen species (ROS), the hydrogel splits and promotes the activation of DCs and macrophages. Then, oxaliplatin is first released from PIVOT to sculpt tumor immunogenicity by inducing immunogenic cell death (ICD) and causing tumoral DNA fragments exposure simultaneously. Subsequently, the impaired DNA fragments bind to high mobility group protein 1 (HMGB1) forming the DNA-HMGB1 complex. Moreover, exogenous FMS-like tyrosine kinase 3 ligand (Flt-3L) recruits masses of DCs, especially cDC1s, which will endocytose the complex benefiting from TIM-3 blockade (αTIM3) that can reverse tolerogenic DCs. Finally, the endocytosis activates the cGAS-STING pathway of cDC1s, which promotes the secretion of type I IFN that triggers innate immune responses, and CXCL9 which recruits CD8+ effector T cells to initiate the following adaptive immune response against tumor progress. PIVOT achieves nearly 90 % tumor growth inhibition and induces systemic antitumor immune responses. In conclusion, this study focuses on ICD-mediated tumor immunogenicity sculpture and nucleic acid endocytosis-involved tolerogenic DCs reversal, providing a novel paradigm for enhancing DCs-based antitumor immune responses.

An analysis of the influencing factors of depression in older adults under the home care model.

Objectives: To explore and analyze the influencing factors of depression in older adults living at home, so as to propose suggestions for improving the quality of older adults living at home. Methods: We conducted a cross-sectional study on 498 older adults living at home based on questionnaire survey on the general information, daily living ability, health status, and care perception (including self-care, care for cohabitants, and care for non-cohabitants) of older adults living at home, as well as their willingness to help each other, and analyzed the influencing factors of depression among older adults living at home. Results: The results showed a willingness to help older adults, self-care, and total activities of daily living (ADL), health status was an influential factor for depression in older adults (p < 0.05). Conclusion: It aims to take targeted measures, such as encouraging older adults at home to actively participate in mutual assistance activities for older adults and care for themselves, so as to prevent and reduce the occurrence of depression in older adults.

Factors associated with the perceived need for assistance from voluntary services in home-based older adults in Chinese urban areas: a cross-sectional study.

BACKGROUND: With China's rapidly aging population, meeting the diverse care needs of senior citizens is becoming more challenging. Although voluntary social services have numerous advantages and are popular among older adults, there is little information on the need for assistance from volunteer-based social services, particularly those with a medical background, and influencing factors among urban home-based older adults. This study aimed to assess the need for assistance from voluntary services and related factors among urban home-based older adults in China. METHODS: A cross-sectional study was conducted in 2022 on communities in four cities in China. The 27-item Home-Based Older Adults Assistance Need Scale was used to measure the assistance needs of 498 participants aged 60 and above. Multiple linear regression models were conducted to identify salient variables associated with the need for assistance from voluntary services. RESULTS: The mean score of the need for assistance from voluntary services was 88.60 ± 24.37. The mean scores of the items examining four dimensions, namely, health maintenance, visiting communication, social intercourse, and daily life, were 3.64 ± 1.08, 3.49 ± 1.04, 3.33 ± 1.08, and 2.78 ± 1.08, respectively. The level of depression, willingness to assist older adults, attaching importance to health preservation, ability to self-comfort, desire to accept assistance from others, and the presence of more children or none at all were all positively correlated with the perceived need for assistance from voluntary services. In contrast, social care obtained from visiting medical institutions was negatively correlated. These seven factors explained 28.5% of the total variance. CONCLUSIONS: Urban home-based older adults in China were found to have significant requirements for assistance from volunteer services, and several complex factors were associated with more significant assistance needs. These findings may encourage the extremely limited numbers of social volunteers, particularly those with a medical background, to identify priorities in providing assistance services to the large numbers of urban home-based older adults and thus improve service delivery.

Antigenicity and adjuvanticity co-reinforced personalized cell vaccines based on self-adjuvanted hydrogel for post-surgical cancer vaccination.

Cancer vaccine-based postsurgical immunotherapy is emerging as a promising approach in patients following surgical resection for inhibition of tumor recurrence. However, low immunogenicity and insufficient cancer antigens limit the widespread application of postoperative cancer vaccines. Here, we propose a "trash to treasure" cancer vaccine strategy to enhance postsurgical personalized immunotherapy, in which antigenicity and adjuvanticity of purified surgically exfoliated autologous tumors (with whole antigen repertoire) were co-reinforced. In the antigenicity and adjuvanticity co-reinforced personalized vaccine (Angel-Vax), polyriboinosinic: polyribocytidylic acid (pIC) and tumor cells that have undergone immunogenic death are encapsulated in a self-adjuvanted hydrogel formed by cross-linking of mannan and polyethyleneimine. Angel-Vax exhibits an enhanced capacity on antigen-presenting cells stimulation and maturation compared to its individual components in vitro. Immunization with Angel-Vax provokes an efficient systemic cytotoxic T-cell immune response, contributing to the satisfied prophylactic and therapeutic efficacy in mice. Furthermore, when combined with immune checkpoint inhibitors (ICI), Angel-Vax effectively prevented postsurgical tumor recurrence, as evidenced by an increase in median survival of approximately 35% compared with ICI alone. Unlike the cumbersome preparation process of postoperative cancer vaccines, the simple and feasible approach herein may represent a general strategy for various kinds of tumor cell-based antigens in the inhibition of postsurgical tumor relapse by reinforced immunogenicity.

Experiences of older people, healthcare providers and caregivers on implementing person-centered care for community-dwelling older people: a systematic review and qualitative meta-synthesis.

BACKGROUND: Person-centered care (PCC) is a critical approach to improving the quality of care for community-dwelling older people. Old-age care services could be provided according to older peoples' choices, needs, and preferences. The purpose of this study was to synthesize research evidence on the experiences of older people, healthcare providers, and caregivers with PCC and to identify the enablers and barriers to implementing PCC for community-dwelling older people. METHODS: A meta-synthesis of qualitative research design was adopted. Data searches were performed using CINAHL (EBSCOhost), PubMed (OvidSP), Embase (Ovid), Cochrane Database, and PsycINFO (Ovid) in published articles and were reviewed from the earliest date to February 2023. The Qualitative Method Appraisal Tool was used to conduct a quality appraisal on selected articles. Data were extracted based on the capacity, opportunity, and motivation-behavior model (COM-B model), and the findings were synthesized using the meta-aggregative approach. RESULTS: Twelve included articles were analyzed to identify 122 findings that were organized into 11 categories and combined into three synthesized findings-capacities of older people, healthcare providers, and caregivers; opportunities in the implementation of PCC; motivation in implementing PCC. Capacities consisted of a lack of person-centered knowledge and skills, negative attitudes toward shared decision-making, and a lack of formal training to enhance capabilities among HCPs. Opportunities included a lack of coordination in resource allocation, strengthening multidisciplinary teamwork, establishing a desirable environment, and time constraints. Motivation in implementing PCC included encouraging self-reflection and regulation, respecting the autonomy of older people, lack of clear reward and empowerment mechanisms, and being resilient and optimistic. CONCLUSIONS: The findings of this research provide a reference for implementing successful PCC in the community. The researchers identified barriers and facilitators of implementing PCC, facilitating through stakeholder's person-centered knowledge and skills being valued and respecting the autonomy of older people. Establishing a positive environment and strengthening multidisciplinary team members also promotes the implementation of PCC. However, additional studies are required to explore the influencing factors and address the barriers.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

Survival Advantages in Gastric Cancer Patients Receiving Preoperative SOX Regimen Chemotherapy.

Objective: This study addressed whether preoperative chemotherapy (PECT) plus surgery prolongs overall survival (OS) compared with surgery plus postoperative chemotherapy (POCT) among gastric cancer (GC) patients in Northwest China. Materials and Methods: The authors included 157 GC patients confirmed histologically or by gastroscopic pathological examination treated at the General Hospital of Ningxia Medical University of China between 2012 and 2018. All patients were followed up by telephone in January 2019 within a 2-week period. The endpoint was death due to GC or its complications. Results: Thirty-eight patients received PECT, 41 patients received POCT, 40 patients received surgery alone, and 38 patients received chemotherapy alone. Surgery was performed with R0 resection and subsequent extended lymph node dissection. Chemotherapy was performed with the S-1, oxaliplatin capecitabine regimen. Patients who received PECT had longer OS than those with POCT treatment (hazard ratio = 2.409, p = 0.037). The 5-year OS rate was 32.7% higher in the PECT group than in the POCT group. Conclusions: PECT was associated with better OS in GC patients and should be considered by clinicians in GC treatment, although prospective studies are needed for confirmation.

Experiences and expectations of receiving volunteer services among home-based elderly in Chinese urban areas: A qualitative study.

BACKGROUND: The various complex needs for assistance among home-based older adults have increased dramatically. Thus, it would be advantageous to recruit volunteers with medical knowledge and a better understanding to support and assist the elderly living in urban communities. AIM: This study aimed to explore the experiences and expectations of receiving volunteer services among the home-based elderly in Chinese urban areas. DESIGN, SETTING AND PARTICIPANTS: A descriptive qualitative study was conducted following the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. This study was performed in two communities in Wuhan, Hubei Province. A purposive sampling method, which includes criterion and maximum variation sampling, was used to identify and select a diverse range of participants. Semistructured face-to-face interviews with 20 older adults (aged 62-90 years old) were performed. The conventional content analysis method was used for thematic analysis. RESULTS: Three categories with associated subcategories were identified: experiences of receiving volunteer services including negative and positive experiences; specific needs for volunteer services involving physiological, psychosocial, health-related behaviours and environmental domains; characteristics of expected volunteer services including availability, formats, recipients, providers and service strategies. CONCLUSIONS: The volunteer services provided to the home-based elderly were found to be unsatisfactory, and lacking relevance and effectiveness. Due to a lack of family support or difficulty in meeting some high-level needs, the home-based elderly expressed a strong demand for volunteer services involving physiological, psychosocial, health-related behaviours and environmental domains. This finding can provide a basis for developing training plans beneficial to volunteers. Furthermore, the present research clarifies the criteria for selecting volunteers and the necessity of supervising and managing volunteers. Improving the effectiveness and accessibility of urban-community volunteer service may reduce the burden on care institutions and home caregivers while enhancing the quality of life and well-being of the elderly. PATIENT OR PUBLIC CONTRIBUTION: Developing research questions, study design, management and conduct and interpretation of evidence.

Prevalence and risk factors of Helicobacter pylori infection in Ningxia, China: comparison of two cross-sectional studies from 2017 and 2022.

OBJECTIVES: Helicobacter pylori (H. pylori) infection causes a variety of intragastric and extragastric diseases. Despite its decreasing global prevalence, it remains a major public health problem in many developing countries. This study aimed to understand the prevalence of H. pylori infection and its risk factors in five cities of the Ningxia Hui Autonomous Region, an area with high incidence of gastric cancer. METHODS: Cross-sectional studies were conducted in Ningxia from 2017 and 2022, to detect the prevalence of H. pylori using the 14C urea breath test. All participants completed a questionnaire that included demographics, personal habits, household economic characteristics, and previous health status. Multiple logistic regression analyses were used to identify independent factors for H. pylori infection. RESULTS: Our findings demonstrated that the prevalence of H. pylori infection in Ningxia decreased significantly from 60.3% in 2017 to 43.6% in 2022, with an increase in public awareness rate from 35.9% in 2017 to 68.5% in 2022. The lowest infection rate was found in Zhongwei and highest in Guyuan. The prevalence of H. pylori infection was higher among Hui ethnicity, farmers, individuals living in rural areas, individuals with lower income, low education, and those who consumed less fruit. Gallbladder, respiratory, cardiovascular and autoimmune diseases were not associated with H. pylori infection. CONCLUSIONS: The prevalence of H. pylori in Ningxia decreased in the past five years. Ethnicity, location, occupation, income, education, and consumption of fruits were independent risk factors for H. pylori infection in Ningxia. It was not associated with extra-gastric disease.

Attenuated ZHX3 expression is predictive of poor outcome for liver cancer: Indication for personalized therapy.

The zinc-fingers and homeoboxes (ZHX) family members have been characterized as master regulators in cancer initiation and development. The present study performed in silico data-mining with publicly available datasets and immunohistochemistry to assess the expression status of ZHX factors and the corresponding prognostic implications in liver cancer. Increased ZHX3 mRNA expression was associated with favorable overall survival in patients with liver cancer. Subgroups analyses revealed a significant association between the expression of ZHX factors and outcomes in select patient cohorts. Immunohistochemical analysis supported that ZHX3 expression was an independent prognostic indicator for patient survival. These results suggested that dysregulation of ZHX factors is involved in disease progression and ZHX3 expression may serve as a prognostic biomarker for liver cancer.

Aberrant expression of the esophageal carcinoma related gene 4 as a prognostic signature for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) is a lethal cancer with increasing incidence, yet the molecular biomarkers that have strong prognostic impact and also hold great therapeutic promise remain elusive. METHODS: Data mining approaches with a set of publicly accessible databases and immunohistochemistry were used to provide a novel insight into the expression pattern and prognostic significance of the esophageal cancer-related gene (ECRG) family members in HCC. RESULTS: We found that elevated mRNA expression levels of ECRG factors were correlated with better overall survival, relapse-free survival and progression-free survival rates in patients with HCC. Subgroup analyses showed significant associations between ECRG expression and survival outcome in select HCC patients. In addition, immunohistochemical and multivariate analysis confirmed increased ECRG4 expression as an independent prognostic indicator for survival. CONCLUSIONS: Our data suggest that ECRG factors have significant impacts on the survival of HCC patients. The expression of ECRG factors may be involved in HCC progression and could serve as novel biomarkers for predicting more accurate prognosis.

Dysregulation of ECRG4 is associated with malignant properties and of prognostic importance in human gastric cancer.

BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P= 0.018), lymph node metastasis (P= 0.011), invasive depth (P= 0.020), advanced tumor stage (P= 0.002) and poor overall survival (P< 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P< 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and α-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.

Prognostic value and therapeutic implications of ZHX family member expression in human gastric cancer.

Despite significant advances in the early diagnosis and effective treatment of gastric cancer, it remains the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. The zinc-fingers and homeoboxes (ZHX) family of transcriptional repressors has been shown to play a role in multiple types of cancer. However, the prognostic significance of ZHX expression in patients with gastric cancer remains unclear. This work studied the association between differential expression of ZHX mRNA and outcomes in patients with gastric cancer using data from the Oncomine, CCLE, Kaplan-Meier-plotter, and cBioPortal databases. Expression of ZHX3 protein was also measured by immunohistochemistry (IHC) in gastric cancer tissues. We found that increased expression of ZHX1 mRNA and decreased expression of ZHX2 and ZHX3 were correlated with better overall survival (OS) in patients with gastric cancer. Further subgroup analyses identified significant associations between ZHX1 expression and survival in select gastric cancer patients. IHC staining confirmed that the over-expression of ZHX3 was associated with worse OS, and multivariate analyses identified ZHX3 expression as an independent prognostic factor. These results suggest that the ZHX family members may serve as distinct biomarkers and prognostic factors for patients with gastric cancer.

Zoledronic acid exhibits radio-sensitizing activity in human pancreatic cancer cells via inactivation of STAT3/NF-κB signaling.

Background: Although pancreatic cancer is typically radio-sensitive, local treatment failure and metastasis are commonly caused by the development of resistance to radiotherapy. In the current study, the radio-sensitizing actions of zoledronic acid (ZOL) on pancreatic cancer cells were investigated. Materials and methods: Three human pancreatic cancer cell lines were exposed to ZOL, ionizing radiation (IR), or a combination of both, and the effects of the respective drug regimens on cell proliferation and invasion were examined. Results: Combined treatment with low doses of ZOL plus IR efficiently increased cell death and attenuated cell invasion compared with the individual use of ZOL or IR. These effects of ZOL were associated with inactivation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB). Conclusion: Collectively, these data suggest that ZOL in combination with IR is a promising therapeutic strategy for enhancing radio-sensitivity in pancreatic cancer cells via downregulation of the STAT3/NF-κB signaling pathway.

Decreased ST2 expression is associated with gastric cancer progression and pathogenesis.

Gastric cancer is a type of cancer with increasing incidence and high mortality rates, but molecular biomarkers of diagnostic and therapeutic value are currently lacking. The aim of the present study was to examine the expression pattern of the interleukin 1 receptor-like 1 (ST2) protein and assess its clinicopathological significance in gastric cancer. Western blot analysis of 12 gastric cancer specimens and paired adjacent tissues demonstrated that the protein levels of 2 isoforms of ST2, soluble secreted ST2 and the ST2 variant without the third immunoglobulin motif and splicing in the C-terminal, were markedly decreased in cancer tissues compared with non-cancerous tissues. Immunohistochemical analysis demonstrated that ST2 protein expression was markedly decreased in primary gastric cancer tissues (39.1%, 90/230) compared with adjacent non-cancerous tissues (60.7%, 54/89) (P<0.05). Statistical analysis demonstrated that decreased ST2 expression was significantly associated with advanced tumor node metastasis stage (P<0.001) and tumor differentiation (P<0.001). These data suggest that ST2 protein may be a valuable biomarker of gastric cancer progression and pathogenesis.

Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients.

BACKGROUND: The ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer. MATERIALS AND METHODS: The mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan-Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes. RESULTS: We found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor. CONCLUSION: Dysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer.