Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

Ion-Pair-Enhanced Double-Click Driven Cell Adhesion and Altered Expression of Related Genes.

Bio-orthogonal ligations that crosslink living cells with a substrate or other cells require high stability and rapid kinetics to maintain the nature of target cells. In this study, we report water-soluble cyclooctadiyne (WS-CODY) derivatives that undergo an ion-pair enhanced double-click reaction. The cationic side chain of WS-CODY accelerated the kinetics on the azide-modified cell surface due to proximity effect. Cationic WS-CODY was able to crosslink azide-modified, poorly adherent human lung cancer PC-9 cells not only to azide-grafted glass substrates but also to other cells within 5-30 min. We discovered that cell-substrate crosslinking induced the ITGA5 gene expression, whereas cell-cell crosslinking induced the CTNNA1 gene, according to the adhesion partner. Ion-pair-enhanced WS-CODY can be applied to a wide range of cells with established azide modifications and is expected to provide a powerful tool to regulate cell-substrate and cell-cell interactions.

Angiographic flow velocity predicts lower limb outcomes after endovascular therapy: Application of the frame count method.

INTRODUCTION: Several factors related to lesion characteristics and endovascular therapy (EVT) procedures have been reported to affect primary patency after EVT. However, it is unknown why these factors were associated with primary patency. We hypothesized patency failure was related to poor blood flow in affected arteries. METHODS: This retrospective study included 131 consecutive patients who had received EVT with bare metal stents for peripheral artery disease caused by femoropopliteal artery lesions. Based on the tertile post-EVT flow velocity of the superficial femoral artery (SFA), patients were divided into high (n = 43), middle (n = 44), and low (n = 44) flow velocity groups. Flow velocity was measured using the frame count method. We measured incidence of major adverse limb events (MALE), composed of target lesion revascularization (TLR), non-TLR, and major amputation. RESULTS: At a median follow-up period of 22.7 months, MALE had occurred in 7 (16.3%), 10 (22.7%), and 29 (65.9%) of patients from the high, middle, and low SFA flow velocity groups, respectively (p < 0.001). Kaplan-Meier analysis showed incidence of MALE was significantly higher in the patients of low SFA flow velocity (log-rank test χ2 = 38.8, p < 0.001). Multivariate analysis found low SFA flow velocity to be an independent predictor for MALE (hazard ratio: 4.42; 95% CI: 2.27 to 8.60; p < 0.001) as was ankle-brachial index. CONCLUSION: Post-EVT SFA flow velocity for femoropopliteal artery lesions treated with bare metal stents is an independent predictor of limb patency. The frame count method for assessing arterial flow velocity is convenient and has potential for wide applications in EVT.

Elevated Remnant Lipoprotein Related to Adverse Events in Patients with Chronic Limb-Threatening Ischemia after Endovascular Therapy for Below-the-Knee Lesions.

BACKGROUND: The prognosis of patients with chronic limb-threatening ischemia (CLTI) is unacceptably poor, and risk factors are unknown. Serum remnant lipoprotein has been associated with cardiovascular events. The aim of our study was to test the hypothesis that remnant lipoprotein is associated with the prognosis of patients with CLTI. METHODS: This retrospective study included 67 patients with CLTI who had received endovascular therapy (EVT) for de novo below-the-knee lesions. Patients were divided into 2 groups using fasting preoperative value of remnant-like particle cholesterol (RLP-C) with a cutoff value of 5.1 mg/dL into LOW RLP-C (n = 46) and HIGH RLP-C (n = 21). We assessed the differences between the 2 groups in the prevalence of major adverse limb events (MALE), composed of target lesion revascularization and major amputation. RESULTS: At a median follow-up period of 12 months, MALE had occurred in 11 LOW RLP-C patients (23.9%) and 11 HIGH RLP-C patients (52.4%; P = 0.03). Kaplan-Meier analysis showed the prevalence of MALE was significantly higher in HIGH RLP-C than LOW RLP-C (log-rank χ2 = 5.2, P = 0.02). Multivariate analysis found HIGH RLP-C to be an independent predictor for MALE (hazard ratio, 2.6; 95% confidence interval, 1.1-6.1; P = 0.02) along with history of coronary artery disease. CONCLUSIONS: Preoperative remnant lipoprotein was associated with the prognosis of patients with CLTI who had received EVT for de novo below-the-knee lesions.

A case of primary orbital solitary fibrous tumor with lung metastases 41 years after initial treatment.

Here, we report a case of an orbital solitary fibrous tumor (SFT) with multiple local recurrences, even after orbital exenteration, and lung metastases after 41 years. The report discusses the clinical and histopathological findings of this case. A 34-year-old female patient with an orbital SFT was treated with orbital exenteration after local resection failed to prevent a recurrence. Ten years later, the patient underwent radiation therapy, followed by two rounds of gamma knife treatment, leading to remission. Forty-one years after the first treatment, the patient, at the age of 75 years, was found to have lung metastases along with orbital recurrence for the eighth time. The patient underwent radiation therapy but died from radiation pneumonitis. Our case emphasizes the need for long-term follow-up of patients with orbital tumors, even after orbital exenteration, to monitor for metastasis.

Clinical Outcomes after Endovascular Therapy Among Hemodialysis Patients with Peripheral Artery Disease Stratified by the Primary Kidney Disease.

OBJECTIVES: The objective of this study was to investigate the clinical characteristics of hemodialysis patients with peripheral artery disease (PAD) and the outcomes after endovascular therapy (EVT) in such patients stratified by the primary kidney disease. METHODS: This retrospective observational study evaluated 142 consecutive hemodialysis patients with symptomatic PAD who underwent EVT (men: n = 103, age: 74 ± 8 years). Patients were divided into 3 groups in accordance with the reason for hemodialysis: hypertensive nephrosclerosis (HTN [n = 26]), diabetic nephropathy (DN [n = 85]), and chronic glomerulosclerosis (CGN [n = 31]). The primary outcome was major adverse event(s) (MAEs), including target lesion revascularization, major amputation, and all-cause death. Clinical characteristics and outcomes were compared among the 3 groups. RESULTS: Patients with HTN were older (81 ± 6 years vs. 72 ± 8 years vs. 74 ± 8 years; P < 0.001) and had a shorter hemodialysis vintage (2.4 years vs. 6.8 years vs. 11.2 years; P < 0.001) than those with DN and CGN. Critical limb ischemia (CLI) affected 15 (58%) patients in the HTN group, 52 (61%) in the DN group, and 10 (32%) in the CGN group. Target lesion length was longer in patients with HTN than in those in the other groups (155 ± 101 mm vs. 108 ± 77 mm [DN] vs. 98 ± 76 mm [CGN]; P = 0.020). During a median follow-up period of 372 days (interquartile range, 198-730 days), Kaplan-Meier curve analysis revealed that HTN was associated with an increased risk for MAEs (χ2 11.6; P = 0.003). Furthermore, multivariate Cox regression analysis revealed that CLI, HTN, and B-type natriuretic peptide levels were independent predictors of MAE (hazard ratio 3.91, 2.88, and 1.00; P < 0.001, P < 0.001, and P = 0.001, respectively). CONCLUSIONS: Among hemodialysis patients with PAD, HTN was associated with an increased risk for MAEs after EVT.

Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5.

Osteoarthritis is a common disease in joint cartilages. Because the molecular pathogenesis of osteoarthritis remains elusive, early diagnostic markers and effective therapeutic agents have not been developed. To understand the molecular mechanisms, we attempted to identify transcription factors involved in the onset of osteoarthritis. Microarray analysis of mouse articular cartilage cells indicated that retinoic acid, a destructive stimulus in articular cartilage, up-regulated expression of sex-determining region Y-box (Sox)4, a SoxC family transcription factor, together with increases in Adamts4 and Adamts5, both of which are aggrecanases of articular cartilages. Overexpression of Sox4 induced a disintegrin-like and metallopeptidase with thrombospondin type 4 and 5 motif (ADAMTS4 and ADAMTS5, respectively) expression in chondrogenic cell lines C3H10T1/2 and SW1353. In addition, luciferase reporter and chromatin immunoprecipitation assays showed that Sox4 up-regulated ADAMTS4 and Adamts5 gene promoter activities by binding to their gene promoters. Another SoxC family member, Sox11, evoked similar effects. To evaluate the roles of Sox4 and Sox11 in articular cartilage destruction, we performed organ culture experiments using mouse femoral head cartilages. Sox4 and Sox11 adenovirus infections caused destruction of articular cartilage associated with increased Adamts5 expression. Finally, SOX4 and SOX11 mRNA expression was increased in cartilage of patients with osteoarthritis compared with nonosteoarthritic subjects. Thus, Sox4, and presumably Sox11, are involved in osteoarthritis onset by up-regulating ADAMTS4 and ADAMTS5.-Takahata, Y., Nakamura, E., Hata, K., Wakabayashi, M., Murakami, T., Wakamori, K., Yoshikawa, H., Matsuda, A., Fukui, N., Nishimura, R. Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5.

Survival and ocular preservation in a long-term cohort of Japanese patients with retinoblastoma.

BACKGROUND: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM). METHODS: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016). RESULTS: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030). CONCLUSIONS: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM.

Stiffening of Cancer Cell Membranes Is a Key Biophysical Mechanism of Primary and Tertiary Cancer Prevention with Green Tea Polyphenols.

Over the past 30 years, research of green tea polyphenols, especially (-)-epigallocatechin gallate (EGCG), has revealed that consumption of green tea is a practical and effective primary cancer prevention method for the general population. More recently, we believe that green tea polyphenols are beneficial for tertiary cancer prevention using green tea alone or combined with anticancer drugs because EGCG has the potential to inhibit metastatic progression and stemness, and enhance antitumor immunity. In an effort to identify a common underlying mechanism responsible for EGCG's multifunctional effects on various molecular targets, we studied the biophysical effects of EGCG on cell stiffness using atomic force microscopy. We found that EGCG acts to stiffen the membranes of cancer cells, leading to inhibition of signaling pathways of various receptors. Stiffening of membranes with EGCG inhibited AXL receptor tyrosine kinase, a stimulator of cell softening, motility and stemness, and expression of programmed cell death-ligand 1. This review covers the following: i) primary cancer prevention using EGCG or green tea, ii) tertiary cancer prevention by combining EGCG and anticancer drugs, iii) inhibition of metastasis with EGCG by stiffening the cell membrane, iv) inhibition of AXL receptor tyrosine kinase, a stimulator of cell softening and motility, with EGCG, v) inhibition of stemness properties with EGCG, and vi) EGCG as an alternative chemical immune checkpoint inhibitor. Development of new drugs that enhance stiffening of cancer cell membranes may be an effective strategy for tertiary cancer prevention and treatment.

A Case of Personal Identification Via Postmortem Computed Tomography Confirmation of Aphakic Eyes.

Postmortem computed tomography (PMCT) is used commonly in forensic medicine. Postmortem computed tomography of the head provides information on the eyes and orbits and may reveal intraocular abnormalities. We present a case in which the identity of a deceased man was confirmed by the presence of aphakic eyes detected on PMCT. A decomposed body was found in a house and suspected to be a man in his 40s who lived alone. Autopsy identified pontine hemorrhage as the cause of death. Although signs of previous dental treatment were evident, the storage period of the householder's dental records had expired. He had no family members to provide DNA for a comparative DNA analysis. Postmortem computed tomography before autopsy revealed aphakia (ie, the absence of eye lenses) suggestive of previous ocular surgery. His medical records revealed that he had undergone ocular surgery for secondary glaucoma due to uveitis, which had resulted in artificial aphakia. Peripheral iridectomy scars fully matched the findings in his medical records, thus identifying the body. The unusual finding of artificial aphakia in a man in his 40s facilitated the personal identification in this case. In conclusion, PMCT provides additional information, and the correct interpretation of intraocular PMCT findings by forensic pathologists is crucial.

Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma.

PURPOSE: To determine the factors that may affect the accuracy of vitrectomy cell block technique in detecting atypical lymphoid cells in patients with vitreoretinal lymphoma (VRL). METHODS: We retrospectively reviewed 43 eyes in 39 patients who underwent vitrectomy for definitive histological diagnosis of VRL with vitrectomy cell block technique and/or smear preparation at Kyushu University Hospital from January 2001 to March 2016. The association of detection of atypical lymphoid cells using vitrectomy cell block technique with the following factors was assessed using logistic regression analysis: age at diagnosis, sex, presence or absence of concurrent cataract surgery with vitrectomy, clinical grading of vitreous haze, presence or absence of subretinal tumor infiltration, interval between initial symptoms and vitrectomy, and presence or absence of systemic corticosteroid therapy before vitrectomy. RESULTS: Atypical lymphoid cells were more significantly detected using vitrectomy cell block technique compared to that using smear preparation (p = 0.018). After adjusting for age and sex, concurrent cataract surgery (odds ratio [OR], 10.41; 95% confidence interval [CI], 1.42-76.41) and subretinal tumor infiltration (OR, 5.06; 95% CI, 1.06-24.32) were significantly associated with failure of histological analysis with vitrectomy cell blocks. In multivariable logistic regression analysis, similar results were obtained, although subretinal tumor infiltration was only marginally associated with the detective capability of the technique. CONCLUSION: Vitrectomy cell block technique significantly improved the definitive diagnosis of VRL. Concurrent cataract surgery with vitrectomy and subretinal tumor infiltration were risk factors for failure in vitrectomy cell blocks.

Diffusivity of intraorbital lymphoma vs. inflammation: comparison of single shot turbo spin echo and multishot echo planar imaging techniques.

PURPOSE: To compare the abilities of turbo spin-echo diffusion-weighted imaging (TSE DWI) and multi-shot echo planar DWI (MSh DWI) to discriminate orbital lymphoma from inflammatory lesions. MATERIALS AND METHODS: Twenty-nine patients with pathologically confirmed lymphomas and 39 patients with inflammation were imaged with a 3.0-T system. The apparent diffusion coefficient (ADC) of each lesion was measured. Signal intensities compared to normal grey matter on conventional imaging were also measured. RESULTS: The ADCs derived from the TSE DWI of the lymphomas (0.68 ± 0.14 × 10-3 mm2/s) were significantly lower than those of the inflammation cases (1.04 ± 0.39 × 10-3 mm2/s; p < 0.001). The ADCs derived from MSh DWI could not be used to separate the lymphomas from the inflammation (1.16 ± 0.43 × 10-3 mm2/s vs. 1.36 ± 0.48 × 10-3 mm2/s; p = 0.06). Conventional sequences also could not separate the lymphomas from the inflammation (p > 0.05). The ROC analysis showed the best diagnostic performance with ADCs derived from TSE DWI (the area under the curve: AUC = 0.831) followed by ADC derived from MSh DWI (AUC = 0.633). CONCLUSION: The ADCs derived from TSE DWI might help to differentiate orbital lymphomas from inflammation. KEY POINTS: • ADC of lymphoma was significantly lower than that of inflammation. • ADC derived from TSE DWI showed the best diagnostic performance. • This study was conducted by a 3-T MR scanner.

Invasive meningococcal disease due to a non-capsulated Neisseria meningitidis strain in a patient with IgG4-related disease.

BACKGROUND: Invasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases). CASE PRESENTATION: We report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed. CONCLUSIONS: Our IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient's IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Reverse engineering liver buds through self-driven condensation and organization towards medical application.

The self-organizing tissue-based approach coupled with induced pluripotent stem (iPS) cell technology is evolving as a promising field for designing organoids in culture and is expected to achieve valuable practical outcomes in regenerative medicine and drug development. Organoids show properties of functional organs and represent an alternative to cell models in conventional two-dimensional differentiation platforms; moreover, organoids can be used to investigate mechanisms of development and disease, drug discovery and toxicity assessment. Towards a more complex and advanced organoid model, it is essential to incorporate multiple cell lineages including developing vessels. Using a self-condensation method, we recently demonstrated self-organizing "organ buds" of diverse systems together with human mesenchymal and endothelial progenitors, proposing a new reverse engineering method to generate a more complex organoid structure. In this section, we review characters of organ bud technology based on two important principles: self-condensation and self-organization focusing on liver bud as an example, and discuss their practicality in regenerative medicine and potential as research tools for developmental biology and drug discovery.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced.

Infections with the human malaria parasite Plasmodium falciparum during pregnancy can lead to severe complications for both mother and child, resulting from the cytoadhesion of parasitized erythrocytes in the intervillous space of the placenta. Cytoadherence is conferred by the specific interaction of the parasite-encoded adhesin VAR2CSA with chondroitin-4-sulfate (CSA) present on placental proteoglycans. CSA presented elsewhere in the microvasculature does not afford VAR2CSA-mediated cytoadhesion of parasitized erythrocytes. To address the placenta-specific binding tropism, we investigated the effect of the receptor/ligand arrangement on cytoadhesion, using artificial membranes with different CSA spacing intervals. We found that cytoadhesion is strongly dependent on the CSA distance, with half-maximal adhesion occurring at a CSA distance of 9 ± 1 nm at all hydrodynamic conditions. Moreover, binding to CSA was cooperative and shear stress induced. These findings suggest that the CSA density, together with allosteric effects in VAR2CSA, aid in discriminating between different CSA milieus.

Adsorption of galloyl catechin aggregates significantly modulates membrane mechanics in the absence of biochemical cues.

Physical interactions of four major green tea catechin derivatives with cell membrane models were systemically investigated. Catechins with the galloyl moiety caused the aggregation of small unilamellar vesicles and an increase in the surface pressure of lipid monolayers, while those without did not. Differential scanning calorimetry revealed that, in a low concentration regime (≤10 µM), catechin molecules are not significantly incorporated into the hydrophobic core of lipid membranes as substitutional impurities. Partition coefficient measurements revealed that the galloyl moiety of catechin and the cationic quaternary amine of lipids dominate the catechin-membrane interaction, which can be attributed to the combination of electrostatic and cation-π interactions. Finally, we shed light on the mechanical consequence of catechin-membrane interactions using the Fourier-transformation of the membrane fluctuation. Surprisingly, the incubation of cell-sized vesicles with 1 µM galloyl catechins, which is comparable to the level in human blood plasma after green tea consumption, significantly increased the bending stiffness of the membranes by a factor of more than 60, while those without the galloyl moiety had no detectable influence. Atomic force microscopy and circular dichroism spectroscopy suggest that the membrane stiffening is mainly attributed to the adsorption of galloyl catechin aggregates to the membrane surfaces. These results contribute to our understanding of the physical and thus the generic functions of green tea catechins in therapeutics, such as cancer prevention.

Fast phase-added stereogram algorithm for generation of photorealistic 3D content.

A new phase-added stereogram algorithm for accelerated computation of holograms from a point cloud model is proposed. The algorithm relies on the hologram segmentation, sampling of directional information, and usage of the fast Fourier transform with a finer grid in the spatial frequency domain than is provided by the segment size. The algorithm gives improved quality of reconstruction due to new phase compensation introduced in the segment fringe patterns. The result is finer beam steering leading to high peak intensity and a large peak signal-to-noise ratio in reconstruction. The feasibility of the algorithm is checked by the generation of 3D contents for a color wavefront printer.

Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green Tea Catechins.

Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (-)-epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young's moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young's moduli resulting in increased stiffness (large elasticity) of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment.

Risk Factors and Preventive Effects of Laser Panretinal Photocoagulation for Neovascular Glaucoma after Ophthalmic Stereotactic Radiotherapy.

Purpose: To evaluate the risk factors and the preventive effects of laser panretinal photocoagulation (PRP) for neovascular glaucoma (NVG) after ophthalmic stereotactic radiotherapy. Methods: Twenty-four patients with ocular malignant tumor (such as uveal malignant melanoma, lacrimal gland cancer) who received stereotactic radiotherapy (such as gamma knife, cyber knife) were retrospectively analyzed. Patients were divided into group A without preventive PRP (n=9), and group B with preventive PRP (n=15). Survival curves were plotted using the Kaplan-Meier method and compared between the two groups with the log-rank test. Results: In group A, NVG occurred in 3 patients. In contrast, in group B, no patient encountered NVG. The significant risk factor for NVG was dose-volumes that irradiated the optic disk (p=0.045). The incidence of NVG was significantly reduced in group B compared with group A (p=0.019). Conclusions: Dose-volumes that irradiated the optic disk were risk factors for NVG. PRP is effective in the prevention of NVG.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies.