Developing and validating a nomogram for penile cancer survival: A comprehensive study based on SEER and Chinese data.

OBJECTIVE: The primary aim of this study was to create a nomogram for predicting survival outcomes in penile cancer patients, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) and a Chinese organization. METHODS: Our study involved a cohort of 5744 patients diagnosed with penile cancer from the SEER database, spanning from 2004 to 2019. In addition, 103 patients with penile cancer from Sun Yat-sen Memorial Hospital of Sun Yat-sen University were included during the same period. Based on the results of regression analysis, a nomogram is constructed and validated internally and externally. The predictive performance of the model was evaluated by concordance index (c-index), area under the curve, decision curve analysis, and calibration curve, in internal and external datasets. Finally, the prediction efficiency is compared with the TNM staging model. RESULTS: A total of 3154 penile patients were randomly divided into the training group and the internal validation group at a ratio of 2:1. Nine independent risk factors were identified, including age, race, marital status, tumor grade, histology, TNM stage, and the surgical approach. Based on these factors, a nomogram was constructed to predict OS. The nomogram demonstrated relatively better consistency, predictive accuracy, and clinical relevance, with a c-index over 0.73 (in the training cohort, the validation cohort, and externally validation cohort.) These evaluation indexes are far better than the TNM staging system. CONCLUSION: Penile cancer, often overlooked in research, has lacked detailed investigative focus and guidelines. This study stands as the first to validate penile cancer prognosis using extensive data from the SEER database, supplemented by data from our own institution. Our findings equip surgeons with an essential tool to predict the prognosis of penile cancer better suited than TNM, thereby enhancing clinical decision-making processes.

The predictive significance of chromobox family members in prostate cancer in humans.

PURPOSE: The Chromobox (CBX) family proteins are crucial elements of the epigenetic regulatory machinery and play a significant role in the development and advancement of cancer. Nevertheless, there is limited understanding regarding the role of CBXs in development or progression of prostate cancer (PCa). Our objective is to develop a unique prognostic model associated with CBXs to improve the accuracy of predicting outcomes of patients with PCa. METHODS: Data from TCGA and GEO databases were analyzed to assess differential expression, prognostic value, gene pathway enrichment, and immune cell infiltration. COX regression analysis was utilized to identify the independent prognostic factors that impact disease-free survival (DFS). The expression of CBX2 and FOXP3+ cells infiltration was verified by immunohistochemical staining of clinical tissue sections. In vitro proliferation, migration and invasion assay were conducted to examine the function of CBX2. RNA-seq was employed to examine the CBX2 related pathway enrichment. RESULTS: CBX2, CBX3, CBX4, and CBX8 were upregulated, while CBX6 and CBX7 were downregulated in PCa tissues. CBXs expression varied by stage and grade. Elevated expression of CBX1, CBX2, CBX3, CBX4 and CBX8 is correlated with poor outcome. CBX2 expression, T stage, and Gleason score were independent prognostic factors. The expression level of CBX2 in PCa tissues was significantly higher than that in adjacent normal tissues. More Treg infiltration was observed in the group with high CBX2 expression. CBX2 expression affected PCa cell growth, migration, and invasion. CONCLUSIONS: CBX2 is involved in the development and advancement of PCa, suggesting its potential as a reliable prognostic indicator for PCa patients.

Post-endoscopic submucosal dissection phlegmonous enteritis: A case report and literature review.

Background: This study presents the initial case of phlegmonous enteritis following endoscopic submucosal dissection (ESD), a rare and potentially fatal complication. Additionally, a comprehensive review of relevant literature is provided. Case report: A 66-year-old female patient, diagnosed with Hashimoto's thyroiditis and thrombocytopenia, underwent ESD to address a laterally spreading tumor located in the ascending colon. After the procedure, the patient manifested abdominal pain and a high fever, was diagnosed with peritonitis, necessitating an emergency exploratory laparotomy and right hemicolectomy. Subsequent histological examination indicated a significant presence of neutrophil infiltration across all layers of the intestines. The ascites culture yielded the growth of Escherichia coli. Literature review: A search was conducted in the PubMed database to identify case reports conforming to the definition of phlegmonous enteritis proposed by Rokitansky et al. We retrieved about 30 studies regarding phlegmonous enteritis from 1951 to 2022, with around 39 cases. Among these, only 28 patients had comprehensive medical data available. Subsequently, an examination of the literature was undertaken to explore the pathogenesis, prevention, and treatment of phlegmonous enteritis. Conclusion: The possibility of phlegmonous enteritis should be taken into consideration in cases of unexplained acute abdomen, particularly in patients with compromised immunity, in order to provide active surgical and antibiotic interventions.

Establishment of a prognostic risk prediction model incorporating disulfidptosis-related lncRNA for patients with prostate cancer.

PURPOSE: Prostate cancer (PCa) is one of the major tumor diseases that threaten men's health globally, and biochemical recurrence significantly impacts its prognosis. Disulfidptosis, a recently discovered cell death mechanism triggered by intracellular disulfide accumulation leading to membrane rupture, is a new area of research in the context of PCa. Currently, its impact on PCa remains largely unexplored. This study aims to investigate the correlation between long non-coding RNAs (lncRNAs) associated with disulfidptosis and the prognosis of PCa, seeking potential connections between the two. METHODS: Transcriptomic data for a PCa cohort were obtained from the Cancer Genome Atlas database. Disulfidptosis-related lncRNAs (DDRLs) were identified through differential expression and Pearson correlation analysis. DDRLs associated with biochemical recurrence-free survival (BRFS) were precisely identified using univariate Cox and LASSO regression, resulting in the development of a risk score model. Clinical factors linked to BRFS were determined through both univariate and multivariate Cox analyses. A prognostic nomogram combined the risk score with key clinical variables. Model performance was assessed using Receiver Operating Characteristic (ROC) curves, Decision Curve Analysis (DCA), and calibration curves. The functional impact of a critical DDRL was substantiated through assays involving CCK8, invasion, migration, and cell cloning. Additionally, immunohistochemical (IHC) staining for the disulfidptosis-related protein SLC7A11 was conducted. RESULTS: The prognostic signature included AC026401.3, SNHG4, SNHG25, and U73166.1 as key components. The derived risk score from these signatures stood as one of the independent prognostic factor for PCa patients, correlating with poorer BRFS in the high-risk group. By combining the risk score with clinical variables, a practical nomogram was created, accurately predicting BRFS of PCa patients. Notably, silencing AC026401.3 significantly hindered PCa cell proliferation, invasion, migration, and colony formation. IHC staining revealed elevated expression of the dithiosulfatide-related protein SLC7A11 in tumor tissue. CONCLUSIONS: A novel prognostic signature for PCa DDRLs, possessing commendable predictive power, has been constructed, simultaneously providing potential therapeutic targets associated with disulfidptosis, among which AC026401.3 has been validated in vitro and demonstrated inhibition of PCa tumorigenesis after its silencing.

Value of three-dimensional visualization of preoperative prostatic magnetic resonance imaging based on measurements of anatomical structures in predicting positive surgical margin after radical prostatectomy.

Background: Positive surgical margin (PSM) or apical positive surgical margin (APSM) is an established predictive factor of biochemical recurrence or disease progression in prostate cancer (PCa) patients after radical prostatectomy. Since there are limited usable magnetic resonance imaging (MRI)-based models, we sought to explore the role of three-dimensional (3D) visualization for preoperative MRI in the prediction of PSM or APSM. Methods: From December 2016 to April 2022, 149 consecutive PCa patients who underwent radical prostatectomy were retrospectively selected from the Second Affiliated Hospital of Dalian Medical University. According to the presence of PSM or APSM, patients were divided into a PSM group (n=41) and a without PSM group (n=108) and into an APSM group (n=33) and a without APSM group (n=116). Twenty-one parameters, including prostate apical shape, PCa distance to the membranous urethra, and pubic angle, were measured on 3D visualization of MRI. The development of the nomogram models was built by the findings of multivariate logistic regression analysis for significant factors. Results: To predict the probability of PSM, a longer PCa distance to the membranous urethra (OR=0.136, p=0.019) and the distance from the anterior peritoneum to the anterior border of the coccyx (work space AP, OR=0.240, p=0.030) were independent protective factors, while a type 3 prostate apical shape (OR=8.262, p=0.025) and larger pubic angle 2 (OR=5.303, p=0.029) were identified as independent risk factors. The nomogram model presented an area under the curve (AUC) of the receiver operating characteristic curve (ROC) of PSM of 0.777. In evaluating the incidence of APSM, we found that the distance to the membranous urethra (OR=0.135, p=0.014) was associated with a low risk of APSM, while larger pubic angle 1 (OR=4.666, p=0.043) was connected to a higher risk of APSM. The nomogram model showed that the AUC of APSM was 0.755. Conclusion: As 3D visualization for preoperative MRI showed good performance in predicting PSM or APSM, the tool might be potentially valuable, which also needs to be validated by multicenter, large-scale, prospective studies.

Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model.

BACKGROUND: SPOCK3 is a secreted extracellular matrix proteoglycan. This study aimed to investigate the effect of SPOCK3 on the malignant progression of prostate cancer and to construct a prognostic model to predict DFS of patients with prostate cancer. METHODS: Clinical and transcriptome sequencing data for prostate cancer were download from the TCGA and GEO databases. The survival curve showed that SPOCK3 has prognostic significance. GO, KEGG, and GSEA enrichment analysis were used to investigate how SPOCK3 affects the malignant progression of prostate cancer. Based on ESTIMATE and ssGSEA, the relationship between SPOCK3 and immune cell infiltration in prostate cancer tissue was clarified. Univariate and multivariate COX regression analysis was used to identify the independent prognostic factors of prostate cancer OS and to construct a nomogram. The calibration curve and ROC curves were drawn to assess the nomogram's predictive power. RESULTS: The survival curve revealed that patients in the low-expression group of SPOCK3 had a poor prognosis. According to enrichment analysis, SOPCK3-related genes were enriched in collagen-containing extracellular matrix, PI3K-Akt, and MAPK signaling pathway. ESTIMATE analysis revealed that SPOCK3 expression was positively correlated with the interstitial score, immune score, and ESTIMATE score. The results of ssGSEA analysis revealed that the infiltration levels of Mast cells, NK cells, and B cells were higher in the SPOCK3 high expression group. Cox regression analysis showed that SPOCK3 expression level, T and Gleason score were independent risk factors of patient prognosis, and a nomogram was constructed. The ROC curve showed the AUCs of DFS at 2, 3, and 5 years. CONCLUSION: SPOCK3 is a protective factor for DFS in prostate cancer patients. SPOCK3 is significantly associated with immune cell infiltration. The prognostic model constructed based on SPOCK3 has excellent predictive performance.

Can angiogenesis inhibitor therapy cause changes in imaging features of hepatic hemangioma- Initial study.

Background: To observe whether anti-angiogenesis therapy can induce changes in size and enhancement characteristics of hepatic hemangioma. Method: 133 patients with hepatic hemangioma lesions were analyzed and classified into a Bevacizumab group (n=65) and the control group (n=68). The parameters (Volume, CT enhancement ratio, enhancement patterns) of pre-and post-treatment in the bevacizumab and control groups independently calculated and compared by two radiologists. Correlation among the systolic blood pressure, diastolic blood pressure, heart rate with the hemangioma volume was evaluated using Pearson's correlation analysis. Results: The hepatic hemangioma volume was significantly decreased after treatment in the Bevacizumab group (8.6 ± 18.7mL vs.7.3 ± 16.3mL, P<0.05), and there was no significant change in the control group (15.1 ± 19.8mL vs.15.4 ± 20.7mL, P = 0.504). A significant difference in enhancement patterns of hepatic hemangiomas was observed after treatment with Bevacizumab (P<0.01). There was no significant difference in arterial phase (AP)enhancement rate and arterial phase-portal venous phase (AP-PVP) enhancement ratios after treatment in the Bevacizumab and control groups (Ps>0.05).The Pearson correlation results showed that blood pressure, heart rate, and hemangioma volume were unrelated or weakly related before and after bevacizumab treatment under the control of factors including weight, contrast injection scheme and CT scanning scheme. Conclusions: Anti-angiogenesis therapy can cause changes in enhancement pattern and volume of hepatic hemangioma. Radiologists should pay more attention to the reexamination of tumor patients treated with anti-angiogenesis therapy.

HMMR promotes prostate cancer proliferation and metastasis via AURKA/mTORC2/E2F1 positive feedback loop.

Although dysregulated HMMR is linked to prostate cancer (PCa) prognosis, the precise mechanisms remain unclear. Here, we sought to elucidate the role of HMMR in PCa progression as well as underlying mechanism. Herein, we found that upregulation of HMMR frequently observed in PCa samples and was associated with poor prognosis. Additionally, HMMR significantly promoted PCa proliferation and metastasis through gain- and loss-of function approaches in vitro and in vivo. Mechanistically, HMMR may interact with AURKA and elevated AURKA protein level through inhibiting ubiquitination-mediated degradation, which subsequently activated mTORC2/AKT pathway to ensure the reinforcement of PCa progression. Moreover, upregulated E2F1 caused from sustained activation of mTORC2/AKT pathway in turn function as transcription factor to promote HMMR transcription, thereby forming a positive feedback loop to trigger PCa progression. Importantly, administration of the mTOR inhibitor partially antagonised HMMR-mediated PCa progression in vivo. In summary, we not only reveal a novel possible post-translation mechanism mediated by HMMR involved in AURKA regulation, but also describe a positive feedback loop that contributes to PCa deterioration, suggesting HMMR may serve as a potential promising therapeutic target in PCa.

Overall diagnostic accuracy of different MR imaging sequences for detection of dysplastic nodules: a systematic review and meta-analysis.

OBJECTIVE: To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN). METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS: Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T2WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73-0.87), 0.90 (95%CI, 0.86-0.93), 7.04 (95%CI, 4.49-11.04), and 0.24 (95%CI, 0.17-0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84-0.93), 0.75 (0.72-0.79), 3.72 (2.51-5.51), and 0.17 (0.12-0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72-0.83), 0.60 (0.55-0.65), 2.19 (1.55-3.10), and 0.36 (0.23-0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71-0.82), 0.92 (0.89-0.94), 8.74 (5.91-12.92), and 0.24 (0.14-0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN. CONCLUSION: MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN. KEY POINTS: • MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma. • Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before. • Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.

Mitophagy Protects the Retina Against Anti-Vascular Endothelial Growth Factor Therapy-Driven Hypoxia via Hypoxia-Inducible Factor-1α Signaling.

Anti-VEGF drugs are first-line treatments for retinal neovascular diseases, but these anti-angiogenic agents may also aggravate retinal damage by inducing hypoxia. Mitophagy can protect against hypoxia by maintaining mitochondrial quality, thereby sustaining metabolic homeostasis and reducing reactive oxygen species (ROS) generation. Here we report that the anti-VEGF agent bevacizumab upregulated the hypoxic cell marker HIF-1α in photoreceptors, Müller cells, and vascular endothelial cells of oxygen-induced retinopathy (OIR) model mice, as well as in hypoxic cultured 661W photoreceptors, MIO-MI Müller cells, and human vascular endothelial cells. Bevacizumab also increased expression of mitophagy-related proteins, and mitophagosome formation both in vivo and in vitro, but did not influence cellular ROS production or apoptosis rate. The HIF-1α inhibitor LW6 blocked mitophagy, augmented ROS production, and triggered apoptosis. Induction of HIF-1α and mitophagy were associated with upregulation of BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) and FUN14 domain containing 1 (FUNDC1), and overexpression of these proteins in culture reversed the effects of HIF-1α inhibition. These findings suggest that bevacizumab does induce retinal hypoxia, but that concomitant activation of the HIF-1α-BNIP3/FUNDC1 signaling pathway also induces mitophagy, which can mitigate the deleterious effects by reducing oxidative stress secondary. Promoting HIF-1α-BNIP3/FUNDC1-mediated mitophagy may enhance the safety of anti-VEGF therapy for retinal neovascular diseases and indicate new explanation and possible new target of the anti-VEGF therapy with suboptimal effect.

Systematic analysis reveals a lncRNA-miRNA-mRNA network associated with dasatinib resistance in chronic myeloid leukemia.

BACKGROUND: Chronic myelogenous leukemia (CML) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells. CML is a relatively rare disease, mainly affecting elderly patients, but the prevalence of CML is expected to increase dramatically. The tyrosine kinase inhibitors (TKIs) have changed the CML patients' treatment patterns and improved its treatment effect, but drug resistance still remains a significant problem to be solved. Therefore, the identification of biomarkers of CML resistance involved therein is essential for treatment and prognosis prediction. METHODS: Bioinformatics was used to analyze and construct a lncRNA-miRNA-mRNA network of CML resistance to dasatinib and predict key lncRNAs. RESULTS: By screening differentially expressed genes in CML resistant to dasatinib and comprehensively analyzing their functions and signal pathways, the core genes in these differential genes were found, and by predictive analysis of the upstream targets of these core genes. Finally, a network diagram containing lncRNA, miRNA, and mRNA was constructed. CONCLUSIONS: MALAT1 as a lncRNA may be a tumor suppressor in patients with CML. According to our data, MALAT1 may have potential role as a molecular biomarker for the occurrence and development of CML resistance to dasatinib.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Evaluation of the Cell Density and Angiogenesis of Cirrhosis-Related Nodules in an Experimental Rat Model: Comparison and Correlation With Dynamic Contrast-Enhanced MRI.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced MRI (DCE-MRI) are sensitive imaging modalities for detecting liver lesions, but their value in evaluating cirrhosis-related nodules remains unclear. PURPOSE: To investigate whether IVIM-DWI and DCE-MRI can differentiate different types of cirrhosis-related nodules, and whether these modalities can monitor changes in cell density and angiogenesis during the malignant transformation of cirrhosis-related nodules in a rat model STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five male Sprague-Dawley rats with 106 cirrhosis-related nodules (19 regenerative nodules [RNs], 47 dysplastic nodules [DNs], and 40 hepatocellular carcinomas [HCCs]). FIELD STRENGTH/SEQUENCE: IVIM-DWI and DCE sequence at 3.0T MRI. ASSESSMENT: IVIM-DWI parameters (D, D*, f, and apparent diffusion coefficient [ADC]) and DCE-MRI parameters (Ktrans , Kep , and Ve ) were calculated by two radiologists using postprocessing software. The "cell density" and "unpaired arterial ratio" were analyzed with a microscope by two pathologists. STATISTICAL TESTS: MRI parameters were compared among the different types of nodules by one-way analysis of variance or the Kruskal-Wallis test. The Pearson correlation test was used to analyze the correlation of MRI parameters with the pathological types of nodules, cell density, and unpaired arterial ratio. RESULTS: The Ktrans , Kep , and Ve values of HCCs were significantly higher than those of DNs and RNs. D and ADC values were significantly lower in HCCs than in DNs and RNs. There were moderate positive correlations of Ktrans with the pathological types of nodules and the unpaired arterial ratio. Moderate negative correlations were observed among D, ADC, and the pathological types of nodules, between D and cell density, and between ADC and cell density. DATA CONCLUSION: IVIM-DWI and DCE-MRI are valuable in differentiating different types of cirrhotic-related nodules. D and ADC are correlated with changes in cell density during the malignant transformation of cirrhosis-related nodules, while Ktrans is correlated with increased angiogenesis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:812-823.

A simple technique for the correction of maxillonasal dysplasia using customized expanded polytetrafluoroethylene (ePTFE) implants.

BACKGROUND: The treatment of maxillonasal dysplasia in Binder's syndrome using autologous costal bone and cartilage is well established, but postoperative results may be compromised by scarring, unpredictable absorption of transferred autologous tissue, and donor site morbidity. Here, we propose a simple surgical technique to improve maxillonasal dysplasia using an expanded polytetrafluoroethylene (ePTFE) implant. MATERIALS AND METHODS: From February 1999 to May 2014, fifty-eight patients affected by maxillonasal dysplasia with different degrees of flattened nose and midfacial depression underwent surgical correction by augmentation of the nasal dorsum using an "L"-shaped ePTFE and subperiosteal implantation of an inverted "m"-shaped ePTFE at the base of the piriform aperture. The outcome was evaluated based on preoperative and postoperative patient pictures, 3D imaging technology for the assessment of nasolabial angle and facial convexity angle, and a postoperative patient satisfaction survey. RESULTS: Postoperative results showed improved facial aesthetics with a significantly increased nasolabial angle from initially 74.1° ± 8.9° to 93.7° ± 6.1° at 6 months postoperatively (p < 0.05). Temporary discomfort involving upper lip numbness, foreign body sensation, and stiff smiling expression were complained during the first 3 months postoperatively, but spontaneously resolved within 6 months. Complications included infection (2 cases), implant migration (2 cases), and implant exposure (1 case). The vast majority of patients (95.7%) rated their postoperative outcome as highly improved and improved. CONCLUSION: The present therapeutic strategy provides a simple and effective treatment for the correction of maxillonasal dysplasia with high patient acceptance in a single step approach. Further research is required to determine long-term outcomes.

Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

A study of ¹³¹iodine labeling of indomethacin, its in vivo biological distribution in Lewis-bearing lung cancer, and its induction of apoptosis in lung cancer.

OBJECTIVE: To study the synthesis of 131iodine (I) labeled histamine-indomethacin (His-IN), its in vivo distribution in Lewis-bearing mice, and its effects on suppression of Lewis lung cancer growth and induction of apoptosis. METHODS: The present study was carried out in the Experimental Research Center, Sheng Jing Hospital of China Medical University Hospital, Shenyang China between December 2008 and October 2009. Chemical synthesis of His-IN was carried out. Ninety-five C57 mice were allocated into 12 groups, and a series of experiments including the in vivo biological distribution of 131I-His-IN in C57 mice bearing Lewis lung cancer was explored, and the therapeutic effects of IN and 131I-His-IN in lung cancer-bearing mice were assessed through tumor suppression experiments, flow cytometry, and detection of tumor necrosis factor. RESULTS: The 131I-His-IN radionuclide count ratio of the tumor site and surrounding region significantly increased with time, namely, the retention time of 131I-His-IN radionuclide was longer in the tumor site. A 3.0 mg/kg and 3.5 mg/kg 131I-His-IN, as well as 3.0 mg/kg and 3.5 mg/kg IN all had tumor suppression and apoptosis induction effects on tumors, among which the 3.5 mg/kg 131I-His-IN group had significant differences compared with all other groups. CONCLUSION: The 131I-His-IN not only retains the tumor-affinity property of IN, the synergistic effect of these 2 also enhances the tumor suppression and pro-apoptotic function.