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In Situ Monitoring of Thermal Degradation of CH <sub/>3</sub> NH <sub/>3</sub> PbI <sub/>3</sub> Films by Spectroscopic Ellipsometry
摘要： High mobility group A2 (HMGA2) is an architectural transcription factor that promotes human colorectal cancer (CRC) aggressiveness by modulating the transcription of target genes. The degradation of p53 is mediated by murine double minute 2 (MDM2) in a proteasome-dependent manner. Here we report that HMGA2 promotes cell cycle progression and inhibits apoptosis in CRC cells in vitro. We also developed an intestinal epithelial cell-specific Hmga2 knock-in (KI) mouse model. It revealed that the Hmga2 KI promoted chemical carcinogen-induced tumorigenesis in the intestine in vivo. In studying the underlying molecular mechanism, we found that HMGA2 formed a protein complex with p53. The tetramerization domain of p53 (amino acids 294–393) and the three AT-hook domains (amino acids 1–83) of HMGA2 were responsible for their direct interaction. We also found that HMGA2 directly bound to MDM2 and the central acidic and zinc finger domains of MDM2 (amino acids 111–360) were required for interaction with HMGA2. Furthermore, our results indicated that HMGA2 promoted MDM2-mediated p53 ubiquitination and degradation. Interestingly, Hmga2 overexpression in Hmga2 KI mice resulted in an increase in the accumulation of ubiquitinated p53. In addition, in two large CRC cohorts, it was demonstrated that high HMGA2 expression was predictive of an adverse outcome in the p53-negative subgroup of CRC patients. In summary, our data have established for the first time a novel mechanism by which HMGA2 functions with p53 and MDM2 to promote CRC progression.
关键词： high mobility group AT-hook 2,colorectal cancer,p53
更新于2025-09-23 15:23:52
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In Search for Optimal Targets for Intraoperative Fluorescence Imaging of Peritoneal Metastasis From Colorectal Cancer
摘要： Peritoneal metastasis (PM) occurs in about 10% of patients with colorectal cancer (CRC). Fluorescence imaging can enhance contrast between cancerous and benign tissue, enabling the surgeon to clearly visualize PM during cytoreductive surgery. This study assessed the suitability of different biomarkers as potential targets for tumor-targeted imaging of PM of CRC. Tissue samples from primary tumor and PM from patients with CRC were obtained from the pathology archives and immunohistochemical stainings were performed. Overexpression of the epithelial cell adhesion molecule (EpCAM) and carcinoembryonic antigen (CEA) was seen in 100% of PM samples and the expression was strong in >70% of samples. Tyrosine-kinase Met (C-Met) and folate receptor α overexpression was seen in 20% of PM samples. For successful application of tumor-targeted intraoperative fluorescence imaging of PM, biomarkers need to be identified. We demonstrated that both EpCAM and CEA are suitable targets for fluorescence imaging of PM in patients with CRC.
关键词： peritoneal metastasis,biomarkers,colorectal cancer,metastasis,Image-guided surgery,fluorescence
更新于2025-09-23 15:22:29
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The capabilities and hope of the combination the new forms of personalized colon cancer treatment – immunotherapy and immune photodynamic therapy
摘要： Introduction: PDT can interfere with cytokine-mediated responses that play an important role in the processes of cancer progression, tumor angiogenesis and metastasis. Therefore, based on the identification of these cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy. Method: We reviewed the major approaches on the use of immunotherapy in colorectal cancer, with the special regard to photodynamic therapy, its immunological effect and new oncological treatment directions, connected with adjuvant immunotherapy including use of nanoparticles. Databases such as PubMed, ScienceDirect and Springer were utilized to search the literature for relevant articles. Purpose: To review studies of the immunotherapy in colon cancer and immune response to PDT. Conclusion: Based on the identification of immunological cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy.
关键词： cytokines,photodynamic therapy,colorectal cancer,immunotherapy
更新于2025-09-23 15:22:29
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Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues
摘要： We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69 cancer tissues removed from the colons of normal and orthotopic mouse models of human colorectal cancer, respectively, demonstrated that the nanobeacon detected colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with colorectal tumors. Histological evaluation revealed that 9 patients suffered from cancer and the rest had adenoma. Mean fluorescence intensities of tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in cancer patients with a high probability (89%); however, the probability reduced to 50% in adenoma patients. There was a reasonable likelihood for diagnosis of colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.
关键词： Colorectal cancer,Diagnostic agent,Optical imaging,Peanut agglutinin,Biomarker imaging,Nanosphere,Thomsen-Friedenreich antigen
更新于2025-09-23 15:22:29
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The Strong Inhibitory Effect of Combining Anti-Cancer Drugs AT406 and Rocaglamide with Blue LED Irradiation on Colorectal Cancer Cells
摘要： There is still no satisfying method to treat colorectal cancer (CRC) currently. Inspired by cocktail therapy, the combination of 465 nm blue LED irradiation and two multi-target anticancer agents AT406 and Rocaglamide has been investigated for a revolutionary way to treat colorectal cancer cells in vitro. It showed a strong inhibitory effect on colorectal cancer cells, and its side effects on human normal cells are negligible. When applied to HCT116 cells, it can achieve an apoptotic rate up to 95%. It is also seen to significantly inhibit proliferation of HT29 cells. Furthermore, little to no cell inhibition or damage of normal MRC-5 cells were seen after treatment. The combination of blue LED irradiation and two anti-cancer drugs causes apoptosis of colorectal cancer cells by activating the apoptotic pathway, inhibiting autophagy and proliferation pathways as well as the production of reactive oxygen species (ROS).
关键词： Multi-targeted anticancer drugs,Colorectal cancer,Inhibitory effect,Blue LED irradiation
更新于2025-09-23 15:21:01
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Synthesis and analysis of 64Cu-labeled GE11-modified polymeric micellar nanoparticles for EGFR-targeted molecular imaging in a colorectal cancer model
摘要： Polymeric micellar nanoparticles represent versatile and biocompatible platforms for targeted drug delivery. However, tracking their biodistribution, stability, and clearance profile in vivo is challenging. The goal of this study was to prepare surface-modified micelles with peptide GE11 for targeting the epidermal growth factor receptor (EGFR). In vitro fluorescence studies demonstrated significantly higher internalization of GE11-micelles into EGFR-expressing HCT116 colon cancer cells versus EGFR-negative SW620 cells. Azo coupling chemistry of tyrosine residues in the peptide backbone with aryl diazonium salts was used to label the micelles with radionuclide 64Cu for positron emission tomography (PET) imaging. In vivo analysis of 64Cu-labeled micelles showed prolonged blood circulation and predominant hepatobiliary clearance. The biodistribution profile of EGFR-targeting GE11-micelles was compared with non-targeting HW12-micelles in HCT116 tumor-bearing mice. PET revealed increasing tumor-to-muscle ratios for both micelles over 48 h. Accumulation of GE11-containing micelles in HCT116 tumors was higher compared to HW12-decorated micelles. Our data suggest that the efficacy of image-guided therapies with micellar nanoparticles could be enhanced by active targeting, as demonstrated with cancer biomarker EGFR.
关键词： polymeric micelles,epidermal growth factor receptor (EGFR),64Cu,GE11 peptide,Colorectal cancer,positron emission tomography (PET)
更新于2025-09-23 15:21:01
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Intraoperative radiotherapy with low energy photons in recurrent colorectal cancer: a single centre retrospective study
摘要： Aim of the study: Intraoperative radiotherapy (IORT) may improve outcome of surgical treatment of recurrent colorectal cancer (CRC). The aim of this study is to determine the feasibility, safety and long-term results of surgical treatment of recurrent CRC with orthovolt IORT. Material and methods: Fifty-nine consecutive CRC patients with local recurrence (LR), undergoing surgery, were included in the retrospective analysis of prospectively collected data. The modified Wanebo classification was used to stage LR (Tr). Twenty-five (43%) patients received IORT using INTRABEAM? PRS 500. The complications were classified according to the Clavien-Dindo classification. Results: There were 32 males and 27 females, with a median age of 63 years. Multi-visceral resections were performed in 37 (63%) patients. Median hospitalization time after surgery with IORT was 7 days. One (1.7%) in-hospital postoperative death was reported. Grade 3/4 postoperative complications were found in 11 (19%) patients. Intraoperative radiotherapy had no effect on the postoperative hospitalization time, morbidity and mortality. Median survival after R0 resection was 32 months. Complete resection (R0), no synchronous liver metastases (M0), and no lateral and posterior pelvic wall involvement, were significant predictors of improved survival. Stage of LR was found to be an independent prognostic factor in the multivariate analysis (p = 0.03; Cox regression model). In patients with LR stage < Tr5, a 3-year overall survival (OS) rate was 52%. Conclusions: Combination of surgical resection and orthovolt IORT is a safe and feasible procedure that does not increase the risk of postoperative complications or prolongs the hospital stay. Despite aggressive surgery supported by IORT, the advanced stage of LR is a limiting factor of long-term survival.
关键词： colorectal cancer,recurrence,intraoperative radiotherapy,survival,surgery
更新于2025-09-23 15:21:01
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A molecular ferroelectrics induced electroactive β-phase in solution processed PVDF films for flexible piezoelectric sensors
摘要： Background: Precise diagnosis of the tissue origin for metastatic cancer of unknown primary (CUP) is essential for deciding the treatment scheme to improve patients’ prognoses, since the treatment for the metastases is the same as their primary counterparts. The purpose of this study is to identify a robust gene signature that can predict the origin for CUPs. Methods: The within-sample relative gene expression orderings (REOs) of gene pairs within individual samples, which are insensitive to experimental batch effects and data normalizations, were exploited for identifying the prediction signature. Results: Using gene expression profiles of the lung-limited metastatic colorectal cancer (LmCRC), we firstly showed that the within-sample REOs in lung metastases of colorectal cancer (CRC) samples were concordant with the REOs in primary CRC samples rather than with the REOs in primary lung cancer. Based on this phenomenon, we selected five gene pairs with consistent REOs in 498 primary CRC and reversely consistent REOs in 509 lung cancer samples, which were used as a signature for predicting primary sites of metastatic CRC based on the majority voting rule. Applying the signature to 654 primary CRC and 204 primary lung cancer samples collected from multiple datasets, the prediction accuracy reached 99.36%. This signature was also applied to 24 LmCRC samples collected from three datasets produced by different laboratories and the accuracy reached 100%, suggesting that the within-sample REOs in the primary site could reveal the original tissue of metastatic cancers. Conclusions: The result demonstrated that the signature based on within-sample REOs of five gene pairs could exactly and robustly identify the primary sites of CUPs.
关键词： Lung cancer,Cancer of unknown primary,Colorectal cancer,Relative gene expression orderings,Metastasis
更新于2025-09-19 17:15:36
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Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells
摘要： To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect. Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells. Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.
关键词： autophagy,apoptosis,photodynamic therapy,chloroquine,sinoporphyrin sodium,colorectal cancer
更新于2025-09-19 17:15:36
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High-Power Dual-End-Pumped Monolithic Tm:YAP Microlaser
摘要： Objective Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE. Methods The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model. Results HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1β, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death. Conclusion Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.
关键词： Baicalin (BI),ApcMin/+ mouse model,Anti-inflammation,Antitumor,Scutellaria baicalensis,Baicalein (BE),Colorectal cancer,Intestinal microbiota
更新于2025-09-12 10:27:22