Exploring the impedance-matching effect in terahertz reflection imaging of skin tissue.

Terahertz (THz) electromagnetic waves, known for their unique response to water, offer promising opportunities for next-generation biomedical diagnostics and novel cancer therapy technologies. This study investigated the impedance-matching effect, which enhances the efficiency of THz wave delivery into tissues and compensates for the signal distortion induced by the refractive index mismatch between the target and the sample substrate. Three candidate biocompatible materials, water, glycerol, and petroleum jelly were applied to a skin phantom and compared using THz two-dimensional imaging and time-of-flight imaging methods. Finally, we successfully demonstrated impedance-matching effect on mouse skin tissues.

C5α secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres.

PURPOSE: Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model. METHODS: PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5α, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays. RESULTS: Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5α, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5α, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5α. CONCLUSIONS: Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5α as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.

Spheroid-Induced Epithelial-Mesenchymal Transition Provokes Global Alterations of Breast Cancer Lipidome: A Multi-Layered Omics Analysis.

Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of SCD, ACOX3, and FADS1 and the down-regulation of PTPLB, PECR, and ELOVL2 were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of ELOVL2. Following mechanistic study confirmed the up-regulation of SCD and down-regulation of PTPLB, PECR, ELOVL2, and ELOVL3 in the spheroid cells. Furthermore, the depletion of ELOVL2 induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of ELOVL2 in basal-like phenotypes. Breast cancer patients with low ELOVL2 expression exhibited poor prognoses (HR = 0.76, CI = 0.67-0.86). Collectively, ELOVL2 expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of ELOVL2 induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes.

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death.

BACKGROUND: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. METHODS: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. RESULTS: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. CONCLUSION: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

Small bowel obstruction from distant metastasis of primary breast cancer: a case report.

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

Photodynamic therapy inhibits melanogenesis through paracrine effects by keratinocytes and fibroblasts.

Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In this study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in vivo. Exposure of MCs to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing MCs to conditioned media of PDT-treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due to a decreased release of melanocyte-stimulating cytokines such as Kit ligand and hepatocyte growth factor from these cells. Furthermore, we observed that PDT reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting the clinical importance of skin whitening by PDT.

Terahertz reflectometry imaging for low and high grade gliomas.

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

Improvement of Terahertz Wave Radiation for InAs Nanowires by Simple Dipping into Tap Water.

We report improvement of terahertz (THz) wave radiation for Si-based catalyst-free InAs nanowires (NWs) by simple dipping into tap water (DTW). In addition, the possibility of using InAs NWs as a cost-effective method for biomedical applications is discussed by comparison to bulk InAs. The peak-to-peak current signals (PPCSs) of InAs NWs measured from THz time-domain spectroscopy increased with increasing NW height. For example, the PPCS of 10 µm-long InAs NWs was 2.86 times stronger than that of 2.1 µm-long NWs. The THz spectra of the InAs NWs obtained by applying a fast Fourier transformation to the current signals showed a main frequency of 0.5 THz, which can be applied to a variety of medical imaging systems. After the DTW process, structural variation was not observed for 2.1 µm-long InAs NWs. However, the top region of several InAs NWs with heights of 4.6 and 5.8 µm merged into a conical structure. InAs NWs with a height of 10 µm resulted in a bundle feature forming above the conical shape, where the length of bundle region was 4 µm. After the DTW process, the PPCS for 10 µm-long InAs NWs increased by 15 percent compared to that of the as-grown case.

Feasibility of terahertz reflectometry for discrimination of human early gastric cancers.

We have investigated the feasibility of THz time-domain reflectometry for the discrimination of human early gastric cancer (EGC) from the normal gastric region. Eight fresh EGC tissues, which were resected by endoscopic submucosal dissection, were studied. Of them, six lesions were well discriminated on THz images and the regions well correlated with tumor regions on pathologically mapped images. Four THz parameters could be suggested for quantitative discrimination of EGCs.

Study of freshly excised brain tissues using terahertz imaging.

We demonstrated that tumors in freshly excised whole brain tissue could be differentiated clearly from normal brain tissue using a reflection-type terahertz (THz) imaging system. THz binary images of brain tissues with tumors indicated that the tumor boundaries in the THz images corresponded well to those in visible images. Grey and white-matter regions were distinguishable owing to the different distribution of myelin in the brain tissue. THz images corresponded closely with magnetic resonance imaging (MRI) results. The MRI and hematoxylin and eosin-stained microscopic images were investigated to account for the intensity differences in the THz images for fresh and paraffin-embedded brain tissue. Our results indicated that the THz signals corresponded to the cell density when water was removed. Thus, THz imaging could be used as a tool for label-free and real-time imaging of brain tumors, which would be helpful for physicians to determine tumor margins during brain surgery.

Measurement depth enhancement in terahertz imaging of biological tissues.

We demonstrate the use of a THz penetration-enhancing agent (THz-PEA) to enhance the terahertz (THz) wave penetration depth in tissues. The THz-PEA is a biocompatible material having absorption lower than that of water, and it is easily absorbed into tissues. When using glycerol as a THz-PEA, the peak value of the THz signal which was transmitted through the fresh tissue and reflected by a metal target, was almost doubled compared to that of tissue without glycerol. THz time-of-flight imaging (B-scan) was used to display the sequential glycerol delivery images. Enhancement of the penetration depth was confirmed after an artificial tumor was located below fresh skin. We thus concluded that the THz-PEA technique can potentially be employed to enhance the image contrast of the abnormal lesions below the skin.

Molecular imaging with terahertz waves.

We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

Risk factors of sagittal decompensation after long posterior instrumentation and fusion for degenerative lumbar scoliosis.

STUDY DESIGN: A retrospective study of clinical results of operative treatment for degenerative lumbar scoliosis. OBJECTIVE: To determine the risk factors of sagittal decompensation after long instrumentation and fusion to L5 or S1. SUMMARY OF BACKGROUND DATA: Little is known about the risk factors for sagittal decompensation, which was defined in this study as sagittal C7 plumb falling anterior >8 cm from the posterosuperior corner of the sacrum. METHODS: Forty-five patients (mean age: 64.4 year) with adult degenerative lumbar scoliosis were reviewed retrospectively with a minimum 2 years. The mean number of levels fused was 6.1 +/- 1.6 segments. The upper instrumented vertebra ranged from T9 to L2. The lower instrumented vertebra was L5 and S1 in 24 and 21 patients, respectively. RESULTS: Sagittal decompensation (SD) developed in 19 patients. The most significant risk factors of SD were preoperative sagittal imbalance and high pelvic incidence. The preoperative sagittal C7 plumb was more positive (67.9 mm) in the decompensation group than in the balance group (37.0 mm) (P = 0.002). There was a significant difference in pelvic incidence between 61.7 degrees in the decompensation and 54.9 degrees in the balance group (P = 0.01). The preoperative lumbar lordosis was hypolordotic in the decompensation group, however, it was not found to be a risk factor. Pseudarthrosis was identified at the lumbosacral junction in 5 patients, and 4 of them (80%) had SD. SD developed in 55% of patients who had loosening of the distal screws and 50% of patients with hypolordotic lumbar fusion. Distal adjacent segment disease was more likely to cause SD than proximal adjacent segment disease. CONCLUSION: Sagittal decompensation is common after long posterior instrumentation and fusion for degenerative lumbar scoliosis. It is mostly associated with complications at the distal segments, including pseudarthrosis and implant failure at the lumbosacral junction. Restoration of optimal lumbar lordosis and secure lumbosacral fixation is necessary especially in patients with preoperative sagittal imbalance and high pelvic incidence in order to prevent sagittal decompensation after surgery.

Nanoparticle-enabled terahertz imaging for cancer diagnosis.

This paper demonstrates the principle of the nanoparticle-contrast-agent-enabled terahertz imaging (CATHI) technique, which yields a dramatic sensitivity of the differential signal from cancer cells with nanoparticles. The terahertz (THz) reflection signal increased beam by 20% in the cancer cells with nanoparticles of gold nano-rods (GNRs) upon their irradiation with a infrared (IR) laser, due to the temperature rise of water in cancer cells by surface plasma ploritons. In the differential mode, the THz signal from the cancer cells with GNRs was 30 times higher than that from the cancer cells without GNRs. As the high sensitivity is achieved by the surface plasmon resonance through IR laser irradiation, the resolution of the CATHI technique can be as good as a few microns and THz endoscopy becomes more feasible.

Smart drug-loaded polymer gold nanoshells for systemic and localized therapy of human epithelial cancer.

Near-infrared-light-sensitive multifunctional smart drug-loaded polymer gold nanoshells are fabricated as advanced prototypes, composed of chemotherapeutic agents (therapeutic antibody and anticancer drug-loaded polymeric nanoparticles) for systemic chemotherapy of human epithelial cancer and a polymer-based gold nanoshell for localized photothermal treatment by NIR light.