Membrane type 1 matrix metalloproteinase regulates anaplastic thyroid carcinoma cell growth and invasion into the collagen matrix.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancer types; however, the molecular mechanism contributing to the aggressive characteristics remain unclear. Membrane type 1 matrix metalloproteinase (MT1-MMP) plays an important role in cancer invasion and has been associated with a poor prognosis in various malignant neoplasms. In this study, we investigated the relationship between MT1-MMP expression and the proliferation and invasion of ATC cells, along with the association with clinicopathologic factors in patients with ATC. Suppression of MT1-MMP reduced the proliferation and invasion of ATC cells, and suppressed ERK activity, indicating a role in cancer cell proliferation in collagen matrix culture conditions. The expression of MT1-MMP was detected in 29 of 34 (85.3%) surgical specimens from ATC patients. In addition, the expression of MT1-MMP in the tumor lesion was higher than that of normal and stromal tissues. Collectively, these results suggest that elevated MT1-MMP expression plays a role in the pathogenesis of ATC, which may promote its aggressive characteristics such as proliferation and invasion, highlighting a potential new therapeutic target.

Expression of fibroblast growth factor receptor 4 and clinical response to lenvatinib in patients with anaplastic thyroid carcinoma: a pilot study.

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS: We investigated FGFR4 expression in patients with ATC and analyzed their clinical responses to lenvatinib. Primary tumor samples were obtained from 12 patients with ATC who underwent surgery or core needle biopsy. FGFR4 protein expression in all ATC samples was analyzed via immunohistochemistry, and the treatment efficacy of lenvatinib was evaluated. RESULTS: The proportion of FGFR4-positive cells in the samples ranged from 0 to 50%. Four patients had partial responses, and three patients had stable diseases as a best clinical response to lenvatinib. The median PFS durations of patients with none, weak, and moderate intensity were 0.5, 3.2 (95% CI 1.1-not estimable [NE]), and 4.6 (95% CI 1.1-NE) months, respectively (p = 0.003). CONCLUSIONS: Because FGFR4 was expressed in ATC tissues, the FGFR4 expression might be associated with the treatment efficacy of lenvatinib in a part of ATC patients. To clarify whether FGFR4 can serve as a prognostic or predictive factor for lenvatinib therapy, more cases must be accumulated.

[Case of Spindle Cell Carcinoma of the Breast Resistant Neoadjuvant Chemotherapy].

We report a rare case of spindle cell carcinoma of the breast which grew rapidly during neoadjuvant chemotherapy. A 72- year-old female was presenting with chief complaint of a mass in the right breast; a tumor about 20 mm in size. Core needle biopsy of tumor revealed invasive ductal carcinoma and fine needle aspiration cytology of axillary lymph node was Class Ⅴ. So she was diagnosis breast cancer as cT2N1M0, cStage ⅡB. The tumor subtype was triple negative breast cancer (TNBC). She received the neoadjuvant chemotherapy by FEC100. After FEC 4 courses, we detected a huge and rapid growing breast mass of 40 mm by CT. She was administered received mastectomy and axillary lymph node dissection after 4 months from initial contact. Pathological finding was spindle cell carcinoma of the breast. Postoperatively, she was treated with weekly PTX for a total of 12 courses and radiation therapy for a right chest wall and supraclavicular fossa. Although the tumor was resistant for neoadjuvant chemotherapy, she is alive and well without metastasis for more than 3 years.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

Projection of multiple directional images on a volume structure with refractive surfaces.

We present a new refraction-based approach to embed multiple images into a single volume structure rendered on a glass solid (3D crystal). Each of the images can only be revealed when looked at from the certain viewpoint. While configurations of viewing directions in conventional methods are limited, our method can compensate for refractive effects at glass surfaces regardless of the viewing directions and enable the viewing directions to be set more flexibly, even allowing for 180 ∘ opposite projection by leveraging refraction. These unique features are verified with prototyping of 3D crystals projecting multiple grey-scale images and numerical assessments. In addition, we present a color dynamic representation of our method with computer graphics to demonstrate the potential use of our method as a novel information service system.

Improvement of an algorithm for displaying multiple images in one space.

Volumetric displays are attracting attention in fields such as media art and digital signage. In previous research, we developed a method to display multiple images in the same space using a volumetric display. However, because of the nature of the algorithm, the images could not be displayed when they contained a pure black image (in which all the pixel values are "0"). In the current study, we present a revised algorithm that can display such images. Therefore, a wider range of images can be displayed in the same space. Image quality evaluation using structural similarity shows that the proposed algorithm yields images that are superior or equivalent to those of the previous algorithm.

Special-purpose computer HORN-8 for phase-type electro-holography.

Electro-holography is a promising display technology that can reconstruct a photorealistic three-dimensional (3D) movie; however, it is yet to be realized practically owing to the need for enormous calculation power. A special-purpose computer for electro-holography, namely HORN, has been studied for over 20 years as a means to solve this problem. The latest version of HORN, HORN-8, was developed using field programmable gate array (FPGA) technology. Initially, a circuit for amplitude-type electro-holography was implemented in HORN-8; however, implementation of phase-type electro-holography has remained an issue. In this paper, the development of new version of HORN-8 and its cluster system, which achieved a real-time reconstruction of a 3D movie with point clouds comprised of 32,000 points for phase-type electro-holography, was reported.

Large-scale electroholography by HORN-8 from a point-cloud model with 400,000 points.

We developed a HORN-8 system that generates computer-generated holograms at a high speed. The cluster system employed eight HORN-8 boards and achieved a level of performance that was 1,000 times faster than that of a PC. From a point-cloud model comprising 65,536 (216) points, the proposed cluster system can update a 2-million-pixel (1,920 × 1,080) hologram at 60 frames per second. 65,536 (216) is the internal memory size of the HORN-8 hardware. However, the HORN-8 system can calculate a hologram at a high speed even if the number of point-cloud sources exceeds 65,536 (216). Herein, we spatiotemporally divided a point-cloud model comprising ~400,000 points and succeeded in reproducing the video-holography. We demonstrated the performance of the special-purpose computer for electroholography using HORN-8 hardware that does not require a large internal memory when the calculation speed is high.

Efficient method for fabricating a directional volumetric display using strings displaying multiple images.

In this study, we describe the fabrication of a high-resolution directional volumetric display that can display multiple images in different directions. The display designs can be used to show animations using strings; however, improving the resolution of such displays is difficult. Previously, the arrangement of strings has only been determined experimentally, making fabrication of volumetric displays a challenge. The goal of the present study is to improve resolution using simulations and to determine the arrangement of strings under three constraints. This simplified the fabrication of a directional volumetric display with 345 strings, which can display two different 20×20 pixel images in two different directions. A large high-resolution directional volumetric display can be fabricated using the proposed method. The string-type display has high artistic potential and is expected to find applications in the amusement and entertainment fields.

Expression of enhancer of zeste homolog 2 correlates with survival outcome in patients with metastatic breast cancer: exploratory study using primary and paired metastatic lesions.

BACKGROUND: In metastatic breast cancer, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as the Ki-67 index sometimes change between primary and metastatic lesions. However, the change in expression levels of enhancer of zeste homolog 2 (EZH2) between primary and metastatic lesions has not been determined in metastatic breast cancer. METHODS: Ninety-six metastatic breast cancer patients had biopsies or resections of metastatic lesions between September 1990 and February 2014 at the Kanagawa Cancer Center. We evaluated ER, PR, HER2, Ki-67, and EZH2 in primary lesions and their corresponding metastatic lesions using immunohistochemistry. We examined the change in expression of EZH2 between primary and metastatic lesions, the correlation between the expression of EZH2 and the expression of other biomarkers, and the relationship between EZH2 expression and patient outcome in metastatic breast cancer. RESULTS: EZH2 expression was significantly higher in metastatic lesions compared with primary lesions. EZH2 expression was highly correlated with Ki-67 expression in primary and metastatic lesions. High-level expression of EZH2 was associated with poorer disease-free survival (DFS) outcomes in patients with primary lesions (P < 0.001); however, high-level expression of EZH2 was not associated with poorer DFS outcomes in patients with metastatic lesions (P = 0.063). High-level expression of EZH2 was associated with poorer overall survival (OS) postoperatively in patients with primary (P = 0.001) or metastatic lesions (P = 0.005). High-level expression of EZH2 was associated with poorer OS outcomes after recurrence in patients with metastatic lesions (P = 0.014); however, high-level expression of EZH2 was not associated with poorer OS outcomes after recurrence in patients with primary lesions (P = 0.096). High-level expression of EZH2 in metastatic lesions was independently associated with poorer OS outcomes after recurrence. CONCLUSIONS: EZH2 expression was significantly increased in metastatic lesions compared with primary lesions. High-level expression of EZH2 in metastatic lesions was associated with poorer OS outcomes after primary surgery and recurrence.

[Efficacy and Safety of Lenvatinib for Unresectable Anaplastic Thyroid Cancer].

The 208 trial showed that lenvatinib has a significant antitumor effect on unresectable anaplastic thyroid cancer(ATC). Herein, we present a retrospective review of data from 7 patients with unresectable ATC who received lenvatinib in our hospital between May 2015 and October 2016. Two patients were men and 5 were women. The median age was 78(range, 72-85)years, and 1 patient had Stage IV A disease, 1 had Stage IV B, and 5 had Stage IV C at diagnosis, respectively. Three patients experienced a partial response and 1 patient experienced stable disease. The response rate was 43%, and the disease control rate was 57%. The median progression-free survival(PFS)was 4.1(range, 1.1-12.2)months. Grade 3 and Grade 4 gastrointestinal hemorrhage were observed in 2patients and Grade 3 anorexia was observed in 1 patient. Further clinical research seems to be needed to establish a treatment strategy involving lenvatinib for ATC.

Image quality improvement for a 3D structure exhibiting multiple 2D patterns and its implementation.

A three-dimensional (3D) structure designed by our proposed algorithm can simultaneously exhibit multiple two-dimensional patterns. The 3D structure provides multiple patterns having directional characteristics by distributing the effects of the artefacts. In this study, we proposed an iterative algorithm to improve the image quality of the exhibited patterns and have verified the effectiveness of the proposed algorithm using numerical simulations. Moreover, we fabricated different 3D glass structures (an octagonal prism, a cube and a sphere) using the proposed algorithm. All 3D structures exhibit four patterns, and different patterns can be observed depending on the viewing direction.

Real-time time-division color electroholography using a single GPU and a USB module for synchronizing reference light.

We propose real-time time-division color electroholography using a single graphics processing unit (GPU) and a simple synchronization system of reference light. To facilitate real-time time-division color electroholography, we developed a light emitting diode (LED) controller with a universal serial bus (USB) module and the drive circuit for reference light. A one-chip RGB LED connected to a personal computer via an LED controller was used as the reference light. A single GPU calculates three computer-generated holograms (CGHs) suitable for red, green, and blue colors in each frame of a three-dimensional (3D) movie. After CGH calculation using a single GPU, the CPU can synchronize the CGH display with the color switching of the one-chip RGB LED via the LED controller. Consequently, we succeeded in real-time time-division color electroholography for a 3D object consisting of around 1000 points per color when an NVIDIA GeForce GTX TITAN was used as the GPU. Furthermore, we implemented the proposed method in various GPUs. The experimental results showed that the proposed method was effective for various GPUs.

Real-time spatiotemporal division multiplexing electroholography with a single graphics processing unit utilizing movie features.

We propose a real-time spatiotemporal division multiplexing electroholography utilizing the features of movies. The proposed method spatially divides a 3-D object into plural parts and periodically selects a divided part in each frame, thereby reconstructing a three-dimensional (3-D) movie of the original object. Computer-generated holograms of the selected part are calculated by a single graphics processing unit and sequentially displayed on a spatial light modulator. Visual continuity enables a reconstructed movie of the original 3-D object. The proposed method realized a real-time reconstructed movie of a 3-D object composed of 11,646 points at over 30 frames per second (fps). We also displayed a reconstructed movie of a 3-D object composed of 44,647 points at about 10 fps.

Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer.

IMPORTANCE: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established. OBJECTIVE: To investigate the relationship between BRAF V600E mutation and PTC-related mortality. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 1849 patients (1411 women and 438 men) with a median age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. MAIN OUTCOMES AND MEASURES: Patient deaths specifically caused by PTC. RESULTS: Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) (P < .001) in BRAF V600E-positive vs mutation-negative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.43 [95% CI, 2.06-9.51]; adjusted HR, 1.46 [95% CI, 0.62-3.47]). In patients with distant tumor metastasis, deaths per 1000 person-years were 87.72 (95% CI, 62.68-122.77) vs 32.28 (95% CI, 16.14-64.55) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 2.63 [95% CI, 1.21-5.72]; adjusted HR, 0.84 [95% CI, 0.27-2.62]). CONCLUSIONS AND RELEVANCE: In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC.

[A case of gastric metastasis and carcinomatous peritonitis of breast cancer with improved QOL by stent implantation and gemcitabine].

A 73-year-old woman had undergone mastectomy for left breast cancer. One year later, bone metastasis was detected. After 7 years, the patient experienced epigastric discomfort, and gastrointestinal endoscopy showed stenosis of the pylorus and enlarged gastric folds. Stomach cancer was suspected at first, but gastric metastasis of breast cancer was diagnosed on the basis of endoscopic reexamination and computed tomography(CT)images. The patient could not drink water, and therefore, gastrointestinal stenting was performed, which facilitated ingestion to some extent. However, at the same time, an elevated serum carcinoembryonic antigen(CEA)level and jaundice were observed. Therefore, biliary tract stenosis due to carcinomatous peritonitis was diagnosed. We attempted to treat the jaundice with endoscopic retrograde cholangiopancreatography( ERCP)or percutaneous transhepatic cholangiography(PTCD), but the treatment was not successful, and an increase in ascites was noted. Accordingly, gemcitabine was administered as systemic therapy. As a result, ascites decreased and jaundice improved. Patients with gastric metastasis of breast cancer have poor quality of life(QOL)because of difficulties in ingestion or vomiting, and poor prognoses, because of frequent concurrent carcinomatous peritonitis. We experienced a case of gastric metastasis and carcinomatous peritonitis, and were able to improve the patient's QOL by gastrointestinal stenting and gemcitabine administration.

Validation of EZH2 Inhibitor Efficiency in Anaplastic Thyroid Carcinoma Cell Lines.

BACKGROUND/AIM: The prognosis of anaplastic thyroid carcinoma (ATC) is poor, and there is currently no established treatment to improve its outcome. We previously reported that enhancer of zeste homolog 2 (EZH2) was highly expressed in ATC, and may be a therapeutic target; however, the effects of EZH2 on ATC growth currently remain unknown. MATERIALS AND METHODS: We investigated the effects of an EZH2 inhibitor (DZNep) on four ATC cell lines (8305C, KTA1, TTA1 and TTA2). We performed a gene panel analysis of all ATC cell lines to identify differences in DZNep sensitivity between the cell lines. To investigate the effects of DZNep on the recovery of differentiation, we assessed changes in thyroid differentiation markers (TDMs) before and after the DZNep treatment using PCR. RESULTS: EZH2 was expressed in all ATC cell lines. The cell-reducing effects of DZNep were detected in all ATC cell lines, and were the strongest in KTA1 cells followed by TTA2 cells. The TTA1 and 8305C cell lines, which showed weak cell-reducing effects, had TP53 mutations. No changes in TDMs were observed in any ATC cell line. CONCLUSION: DZNep, an EZH2 inhibitor, exerted suppressive effects on the growth of ATC cell lines and has potential as a therapeutic strategy; however, its effects may be attenuated in ATC with TP53 mutations.

Generation of real-time large computer generated hologram using wavefront recording method.

We report the generation of a real-time large computer generated hologram (CGH) using the wavefront recording plane (WRP) method with the aid of a graphics processing unit (GPU). The WRP method consists of two steps: the first step calculates a complex amplitude on a WRP that is placed between a 3D object and a CGH, from a three-dimensional (3D) object. The second step obtains a CGH by calculating diffraction from the WRP to the CGH. The disadvantages of the previous WRP method include the inability to record a large three-dimensional object that exceeds the size of the CGH, and the difficulty in implementing to all the steps on a GPU. We improved the WRP method using Shifted-Fresnel diffraction to solve the former problem, and all the steps could be implemented on a GPU. We show optical reconstructions from a 1,980 × 1,080 phase only CGH generated by about 3 × 10(4) object points over 90 frames per second. In other words, the improved method obtained a large CGH with about 6 mega pixels (1,980 × 1,080 × 3) from the object points at the video rate.

Fast high-resolution computer-generated hologram computation using multiple graphics processing unit cluster system.

To overcome the computational complexity of a computer-generated hologram (CGH), we implement an optimized CGH computation in our multi-graphics processing unit cluster system. Our system can calculate a CGH of 6,400×3,072 pixels from a three-dimensional (3D) object composed of 2,048 points in 55 ms. Furthermore, in the case of a 3D object composed of 4096 points, our system is 553 times faster than a conventional central processing unit (using eight threads).

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.