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Impalement injuries are rare and complex problems, often involving multiple organ injuries. An 18-year-old male was admitted to our emergency department after a car accident. Positioned in the right-side recumbent position, he had a 4.5 cm diameter pipe penetrating from his left abdomen to his back. Given the pipe's length exceeding the CT gantry's capacity, further imaging tests were not feasible. Consequently, the patient proceeded directly to the operating room without preoperative imaging. Before laparotomy, a left thoracotomy was conducted for aortic cross-clamping, anticipating uncontrollable bleeding during pipe removal. The subsequent laparotomy, with the patient in the right-side recumbent position, revealed the pipe impaling through the mesentery of the descending colon without evident major vessel injury. The pipe was cautiously extracted. The patient was subsequently discharged on day 26. The absence of imaging feasibility emphasized that current hemodynamic stability does not rule out the potential for significant vessel injury. Therefore, the sequential approach of left thoracotomy for aortic cross-clamping followed by laparotomy emerges as a potentially beneficial strategy in cases of transabdominal impalement. The impalement injury requires our preparedness and flexibility, which should be tailored to the individual case.
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Novel hybrid porphyrin(2.1.2.1)s and their boron and copper complexes were synthesized using the "toy bricks" synthetic method. Crystal data, frontier molecular orbital calculations, and electrostatic potential surface maps reveal that hybridization in the porphyrin(2.1.2.1) donor-acceptor unit controls the selective coordination of BF2.
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To investigate the host ability of a simple macrocycle, 1,3-phenylene-bridged naphthalene hexamer N6, we evaluated the complexation of N6 with fullerenes in toluene and in the crystals. The complexes in the solid-state demonstrate the one-dimensional alignment of fullerenes. The single-crystals of the C60@N6 composite have semiconductive properties revealed by photoconductivity measurements.
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An atropisomerism of large cycloarylenes was studied using [n]cyclo-4,10-pyrenylenes (n=6-21) as an illustrative example with two simple assumptions: (1) alternating configurations (R,S,R,S, ) are thermodynamically most stable, and (2) three consecutive identical configurations (R,R,R or S,S,S) are prevented. Ni-mediated coupling of a 5,9-diiodopyrene gave a series of directly-linked cyclic pyrene oligomers in one-pot reaction. As-synthesized cyclic hexamer was assigned as an (R,S,S,R,R,S) structure, converted into an (R,S,R,S,R,S)-form upon heating. Cyclic heptamer consists of two types of C2 symmetric structures predicted from assumption (2), one of which was convergent to one another by heating. Three atropisomers of cyclic octamer were analyzed from the possible five candidates by means of 1 H nuclear magnetic resonance (NMR) spectroscopy, and the conversion process to (R,S,R,S,R,S,R,S) configurations upon heating was investigated. In total, according to two simple rules, the analysis of atropisomerism could be performed smoothly.
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Novel 24π antiaromatic and 26π aromatic meso-aryl rosarins were successfully obtained for the first time from ß-free bipyrrole through a one-pot synthesis. Because of the absence of substituents at the ß-positions of the pyrrole units, the ß-free pristine rosarin backbones were highly planar, as confirmed using X-ray crystallography. Optical measurements indicated interconversion between 24π antiaromatic and 26π aromatic ß-free pristine rosarin via redox reactions, which was not observed in distorted ß-dodecamethyl rosarin.
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Tumor blood vessels play important roles in tumor progression and metastasis. Targeting tumor endothelial cells (TECs) is one of the strategies for cancer therapy. We previously reported that biglycan, a small leucine-rich proteoglycan, is highly expressed in TECs. TECs utilize biglycan in an autocrine manner for migration and angiogenesis. Furthermore, TEC-derived biglycan stimulates tumor cell migration in a paracrine manner leading to tumor cell intravasation and metastasis. In this study, we explored the therapeutic effect of biglycan inhibition in the TECs of renal cell carcinoma using an in vivo siRNA delivery system known as a multifunctional envelope-type nanodevice (MEND), which contains a unique pH-sensitive cationic lipid. To specifically deliver MEND into TECs, we incorporated cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) into MEND because αV ß3 integrin, a receptor for cRGD, is selective and highly expressed in TECs. We developed RGD-MEND-encapsulating siRNA against biglycan. First, we confirmed that MEND was delivered into OS-RC-2 tumor-derived TECs and induced in vitro RNAi-mediated gene silencing. MEND was then injected intravenously into OS-RC-2 tumor-bearing mice. Flow cytometry analysis demonstrated that MEND was specifically delivered into TECs. Quantitative RT-PCR indicated that biglycan was knocked down by biglycan siRNA-containing MEND. Finally, we analyzed the therapeutic effect of biglycan silencing by MEND in TECs. Tumor growth was inhibited by biglycan siRNA-containing MEND. Tumor microenvironmental factors such as fibrosis were also normalized using biglycan inhibition in TECs. Biglycan in TECs can be a novel target for cancer treatment.
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Carcinoma de Células Renais , Neoplasias Renais , Inibidores da Angiogênese , Animais , Biglicano/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Células Endoteliais , Humanos , Neoplasias Renais/genética , Lipossomos , Camundongos , RNA Interferente Pequeno/genéticaRESUMO
BACKGROUND: Biglycan is a proteoglycan found in the extracellular matrix. We have previously shown that biglycan is secreted from tumor endothelial cells and induces tumor angiogenesis and metastasis. However, the function of stroma biglycan in breast cancer is still unclear. METHODS: Biglycan gene analysis and its prognostic values in human breast cancers were based on TCGA data. E0771 breast cancer cells were injected into WT and Bgn KO mice, respectively. RESULTS: Breast cancer patients with high biglycan expression had worse distant metastasis-free survival. Furthermore, biglycan expression was higher in the tumor stromal compartment compared to the epithelial compartment. Knockout of biglycan in the stroma (Bgn KO) in E0771 tumor-bearing mice inhibited metastasis to the lung. Bgn KO also impaired tumor angiogenesis and normalized tumor vasculature by repressing tumor necrosis factor-É/angiopoietin 2 signaling. Moreover, fibrosis was suppressed and CD8+ T cell infiltration was increased in tumor-bearing Bgn KO mice. Furthermore, chemotherapy drug delivery and efficacy were improved in vivo in Bgn KO mice. CONCLUSION: Our results suggest that targeting stromal biglycan may yield a potent and superior anticancer effect in breast cancer.
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Biglicano/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Células Estromais/metabolismo , Microambiente Tumoral/fisiologia , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Animais , Biglicano/genética , Biglicano/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Feminino , Fibrose/prevenção & controle , Humanos , Camundongos , Camundongos Knockout , Metástase Neoplásica/prevenção & controle , Neovascularização Patológica/genética , Neovascularização Patológica/prevenção & controle , Paclitaxel/uso terapêutico , Prognóstico , Transdução de Sinais , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: In lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients. MATERIALS AND METHODS: First, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN-positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels. RESULTS: High BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy. CONCLUSIONS: BGN can be a potential biomarker for lung cancer.
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Biglicano/uso terapêutico , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Biglicano/farmacologia , Feminino , Humanos , MasculinoRESUMO
Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell-like populations with high aldehyde dehydrogenase (ALDH) activity (ALDHhigh TEC). ALDHhigh TEC have proangiogenic properties compared with ALDHlow TEC. However, the association between ALDHhigh TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor-conditioned medium (tumor CM). The ALDHhigh population increased along with upregulation of stem-related genes such as multidrug resistance 1, CD90, ALP, and Oct-4. Tumor CM also induced sphere-forming ability in HMVEC. Platelet-derived growth factor (PDGF)-A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDHhigh TEC were resistant to fluorouracil (5-FU) in vitro and in vivo. ALDHhigh TEC showed a higher grade of aneuploidy compared with that in ALDHlow TEC. These results suggested that tumor-secreting factor increases ALDHhigh TEC populations that are resistant to 5-FU. Therefore, ALDHhigh TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance.