A fully integrated CMOS circuit based on a vector network analyzer and a transmission-line-based detection window for circulating tumor cell (CTC) and exosome analysis is presented for the first time. We have introduced a fully integrated architecture, which eliminates the undesired parasitic components and enables high-sensitivity, to analyze extremely low-concentration CTC in blood. The detection window was designed on the high-sensitive coplanar waveguide line. To validate the operation of the proposed system, a test chip was fabricated using 65-nm CMOS technology. Measurements were performed after adding a tiny lump of silicone or a droplet of water on its detection window. The measured results show |S_21| degradation of −1.96 dB and −6.04 dB for the silicone and the droplet, respectively, at 1.4 GHz. In addition, in another measurement using magnetic beads, it is confirmed that the proposed circuit can analyze even low concentrations of 20 beads/µL.
Patient: Male, 56Final Diagnosis: Small cell lung carcinomaSymptoms: Back pain • paralysisMedication: —Clinical Procedure: MRISpecialty: PulmonologyObjective:Unusual clinical courseBackground:Spinal cord ischemia is an uncommon event that is mainly caused by dissociation of the ascending aorta as a complication after aortic surgery. Spinal arteries can develop collateral circulation; therefore, the frequency of spinal infarction is about 1% of that in the brain. Few cases of spinal cord ischemia developing in the course of lung cancer have been reported.Case Report:We presented the case of a 56-year-old man with small cell lung carcinoma, cT4N2M1a (stage IV). He was treated with irradiation and 2 courses of platinum and etoposide combination chemotherapy. He complained of back pain followed by quadriplegia and sensory disturbance after cessation of chemotherapy. With a diagnosis of spinal cord metastasis, steroids were administered. However, diaphragmatic paralysis appeared a few hours later. He was started on palliative care and died after 6 days. Autopsy showed epidural metastasis and spinal ischemia at the C5 level.Conclusions:Epidural metastasis can compress the spinal artery and cause circulatory disorders. Spinal cord ischemia should be considered in patients with rapid paralysis in the course of lung cancer.
A fluoropolymer membrane filter with through-holes was fabricated by photolithographic patterning and the dry etching method. 380,000 highly packed through-holes, each with a diameter of 7 µm were able to cover a whole area with a diameter of 13 mm. Ethylene tetrafluoroethylene (ETFE) was used as the membrane, which was suitable for the fluorescence detection of rare cells such as circulating tumor cells (CTCs) in human blood. The device fabrication for the size based capture of rare cells in blood such as CTCs is realized in this study.
Background: Lectin-like oxidized LDL receptor-1 (LOX-1) has been identified as a new marker for functional myeloid-derived suppressor cells (MDSCs) that exhibit an immunosuppressive phenotype in the tumor microenvironment (TME). However, the role of LOX-1 + cells in the TME of colorectal cancer (CRC) remains unknown.Aim: This study aimed to determine the expression and significance of LOX-1 in the TME of clinical CRC specimens.Methods and results: We performed immunohistochemical and genetic analyses of LOX-1, CD8, KRAS, and BRAF in 128 resected CRC specimens and determined the expression of IFN-γ and IL-10 using real-time reverse transcription-polymerase chain reaction. We analyzed the correlation between LOX-1, TME factors, gene alteration, clinicopathological factors, and disease prognosis. The co-expression pattern of LOX-1, hematopoietic markers, and a fibroblast marker was evaluated using multiplex immunofluorescence staining. Low stromal LOX-1 expression and low intratumoral CD8 + cytotoxic T-lymphocyte (CTL) status correlated with poor prognosis. Moreover, stromal LOX-1-low/CD8 + CTL-low status was the most important independent prognostic factor of poor overall survival. Most of the LOX-1 + stromal cells were positive for CD163 + , indicating they were CD163 + M2 macrophages.
Conclusions:The MDSC marker, LOX-1, was mainly expressed by M2 macrophages in CRC tissues. LOX-1 + macrophages and CD8 + CTLs may serve as useful biomarkers for predicting the prognosis of CRC.
Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis.
Background
No standard treatment for anorectal fistula cancer, such as multidisciplinary therapy, has been established due to the rarity of the disease. Herein, we investigated patients with cancer associated with anorectal fistula who underwent surgery to clarify the clinicopathological characteristics and to propose future perspectives for treatment strategies.
Case presentation
Seven patients with cancer associated with anorectal fistula who underwent rectal amputation in our institute were analyzed with regard to clinical characteristics, pathological findings, surgical results, and prognosis. Four cases had Crohn's disease as an underlying cause. All seven cases were diagnosed as advanced stage. Preoperative [18F]-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography/computed tomography (FDG-PET/CT) showed abnormal FDG accumulation in six cases including four mucinous adenocarcinomas. Three cases that received preoperative hyperthermo-chemoradiotherapy achieved pathological R0 resection. Postoperative recurrence was observed in four cases including three with Crohn's disease and one resulting in death.
Conclusions
Anorectal fistula cancer is rare and difficult to be diagnosed at early stages. Mucinous adenocarcinoma associated with anorectal fistula tends to exhibit abnormal FDG accumulation by FDG-PET/CT unlike common colorectal mucinous adenocarcinoma. Preoperative hyperthermo-chemoradiotherapy may be effective in obtaining pathological complete resection.
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