Abstract Malignant bone tumors are often accompanied by osteolytic destruction and severe pathological fractures. Current therapeutic strategies can largely inhibit tumor proliferation, but the high recurrence rate of tumors and related bone defects remain a significant challenge. This study aims to address these issues by developing a novel near‐infrared (NIR) light‐responsive and a mechanically strong hydrogel that offers excellent photothermal tumor therapy and bone fracture repair capabilities. The as‐prepared hydrogel exhibits good biocompatibility and an ultra‐strong photothermal effect due to the formation of a complex network with up‐conversion lanthanide‐Au hybrid nanoparticles and alginate molecules. A subcutaneous tumor model is used to demonstrate that tumors can be efficiently eradicated via local photothermal treatment, where there is no tumor recurrence within the observation period. Moreover, the injected hydrogel becomes mechanically strong due to in situ Ca 2+ crosslinking, which provides a supportive matrix to promote the repair of bone defects via stabilization of the fractured bone structure. The high photothermal effect and robust support offered by this single material demonstrate the potential of using the proposed hydrogel for the simultaneous treatment of bone tumor removal and bone healing.
Abstract Background Colorectal cancer remains an incurable disease despite progress in treatment over the past few years. Methods In this report, we presented a case on colon cancer leading to the development (metastasis) of colorectal cancer in a 56-year-old woman. Preoperative colonoscopy was performed, and diagnosis revealed a malignant tumor of the colon with a tumor of the abdominal wall, a secondary malignant tumor of the abdominal cavity, a malignant tumor of the ovary. The biopsies revealed a metastatic or invasive grade I-II adenocarcinoma. Laparoscopic was performed after few days. Results During the surgery a metastasis of about 3 cm was found and the metastasis of the pelvic cavity showed that the anterior wall of the rectum and the cervical stump have recurrence of about 4 cm and some small intestinal cancerous adhesions were present in the lesion. Afterwards, the biopsy specimens were reanalyzed, and immunohistological analysis shown this as cancerous tissue. Conclusion When colorectal cancer is detected in a patient with a history of colon cancer and bilateral metastatic ovarian adenocarcinoma, the physician should be very observant of the condition as there is the possibility of recidivism due to poor prognosis. Surgery is the only curative treatment for metastatic colorectal cancer.
Activating transcription factor 4 (ATF4) is a DNA-binding protein widely generated in mammals, which has two biological characteristics that bind the cAMP response element (CRE). The mechanism of ATF4 as a transcription factor in gastric cancer affecting the Hedgehog pathway remains unclear. Here, we observed that ATF4 was markedly upregulated in gastric cancer (GC) using immunohistochemistry and Western blotting assays in 80 paraffin-embedded GC samples and 4 fresh samples and para-cancerous tissues. ATF4 knockdown using lentiviral vectors strongly inhibited the proliferation and invasion of GC cells. ATF4 upregulation using lentiviral vectors promoted the proliferation and invasion of GC cells. We predicted that the transcription factor ATF4 is bound to the SHH promoter via the JASPA database. Transcription factor ATF4 is bound to the promoter region of SHH to activate the Sonic Hedgehog pathway. Mechanistically, rescue assays showed that ATF4 regulated gastric cancer cells' proliferation and invasive ability through SHH. Similarly, ATF4 enhanced the tumor formation of GC cells in a xenograft model.
Abstract Objective Carbon nanoparticle has a lymphatic tracing effect, which can be combined with anti-tumor drugs to induce lymph nodes and have a strong inhibitory effect on tumor cells. Evaluate the feasibility and effectiveness of the method. Methods： CCK8 method was used to detect 1. IC50% (50% minimum lethal concentration) of CNP (50ug/ml-1500ug/ml) and RTX (10ug/ml-100ug/ml) on colorectal cancer cells HCT116, 2. Western blotting experiment (western blot, WB) to detect the effect of CNP (500ug/ml) on the apoptosis pathway of colorectal cancer cells HCT116. 3. The inhibitory effect of CNP+RTX (500ug/ml+40ug/ml) on intestinal cancer cells HCT116. Compare the inhibitory effect of pure RTX (40ug/ml). Results : 1. The carbon nanoparticles had antiproliferative toxicity to HCT-116 cells in vitro.2. The IC50% of CNP and RTX on intestinal cancer cells HCT116 were 500ug/ml and 40ug/ml, respectively.3. Carbon nanoparticles promote the apoptosis of intestinal cancer cells HCT116.4. In the in vitro cytotoxicity test, CNP combined with RTX has a strong inhibitory effect on intestinal cancer cell HCT116, which is superior to RTX alone. Conclusions: In vivo studies suggest that colorectal cancer cells HCT116 have obvious apoptosis under the treatment of carbon nanoparticles, and CNP+RTX has a significant inhibitory effect on colorectal cancer cells HCT116. Carbon nanoparticles raltitrexed combined with carbon nanoparticles may be a potential delivery system during lymphatic chemotherapy.
Objectives: Research on the role of mast cells (MCs) in cervical tumor immunity is more limited. Therefore, our study aimed to evaluate the prognostic value of MCs and their correlation with the immune microenvironment of cervical carcinoma (CC). Methods: The Cancer Genome Atlas (TCGA) data was utilized to obtain the degree of immune infiltration of MCs in CC. Meanwhile, this study retrospectively collected patient clinical characteristic data and tissue specimens to further verify the relevant conclusions. Mast cell density (MCD) was measured by the CIBERSORT algorithm in TCGA data and immunohistochemical staining of tryptase in CC tissues. Finally, differentially expressed genes (DEGs) of TCGA data were performed using “limma” packages and key gene modules were identified using the MCODE application in Cytoscape. Results: The results showed MCs were diffusely distributed in CC tissues. Moreover, we found that low tumor-infiltrating MCD was beneficial for overall survival (OS) in the TCGA cohort. Consistent conclusions were also obtained in a clinical cohort. In addition, a total of 305 DEGs were analyzed between the high tumor-infiltrating MCD and low tumor-infiltrating MCD group. Seven key modules, a total of 34 genes, were screened through the MCODE plug-in, which was mainly related to inflammatory response and immune response and closely correlated with cytokines including CSF2, CCL20, IL1A, IL1B, and CXCL8. Conclusion: In short, high tumor-infiltration MCs in CC tissue was associated with worse OS in patients. Furthermore, MCs were closely related to cytokines in the tumor microenvironment, suggesting that they collectively played a role in the immune response of the tumor. Therefore, MCD may be a potential prognostic indicator and immunotherapy target of CC.
As one of the most important transportation hubs and industrial bases in China, Zhengzhou has suffered from serious PM2.5 pollution for a long time. However, the investigation of contamination status and possible exposure risks of environmentally persistent free radicals (EPFRs) in PM2.5 from Zhengzhou is rare. In this work, a comprehensive study of pollution levels, seasonal variations, sources, and potential health risks of PM2.5-bound EPFRs in Zhengzhou was conducted for the first time. The atmospheric concentrations of EPFRs in PM2.5 from Zhengzhou ranged from 1.732 × 1012 spin m-3 to 7.182 × 1014 spin m-3 between 2019 and 2020. Relatively serious contamination was noticed in winter and spring. Primary fossil fuel combustion and Fe-mediated secondary formation were apportioned as possible sources of PM2.5-bound EPFRs in Zhengzhou. Moreover, to avert the bias of the toxicity assessment induced by utilization of incompletely extracted EPFRs from sample filter, simulatively generated EPFRs were applied to toxicological evaluations (cell viability and reactive oxygen species assays). Corresponding experimental dosages were based on the estimated adults' annual exposure amounts of EPFRs in real PM2.5 samples. The results elucidated that EPFRs might cause growth inhibition and oxidative stress of human lung cells, suggesting the possible exposure-induced health concerns for local people in Zhengzhou. This study provides practical information of real contamination status of PM2.5-bound EPFRs in Zhengzhou, which is favorable to local air pollution control and reduction of exposure risks on public health in central China.
Abstract Conventional nanocarriers for oral squamous cell carcinoma (OSCC) chemotherapy are greatly limited due to undesired adverse effects and low bioavailability. As an FDA‐approved protein nanocarrier, i.e., human serum albumin (HSA), the folded conformation limits its versatility for loading OSCC chemotherapeutics with different molecular structures. Here, a new type of biosynthetic and unfolded protein nanocarrier is developed, which shows outstanding efficiency for loading and delivering a series of chemotherapeutic agents, including chlormethine, docetaxel, and pingyangmycin. Moreover, all the nanoformulated drugs exhibit rather prolonged half‐lives as evidenced by sustained release of the payloads for up to 5 days. In stark contrast to polymeric micelles and liposomes, in this system the loading efficiency is increased 3–4 times and the corresponding half‐life is even extended one order of magnitude. Enhanced antitumor effects in rat OSCC models are realized. Additionally, off‐target side effects such as liver and kidney toxicity and immunogenicity are significantly mitigated with the nanomedications. Thus, this versatile formulation strategy boosts the efficacy, bioavailability, and safety of chemotherapeutics in OSCC therapy, and promisingly enables combined chemotherapy in comprehensive treatment for OSCC.
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