Background/Aim: L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers. However, the clinicopathological significance of LAT1 and 4F2 cell surface antigen (4F2hc) in patients with colorectal cancer (CRC) is unknown. The aim of this study was to clarify the prognostic significance of LAT1 expression in CRC patients who underwent surgical resection. Materials and Methods: Samples from one hundred and forty-seven patients were examined by immunohistochemistry. The expression of LAT1 and 4F2hc, and the Ki-67 labeling index were assessed using resected tumor specimens. Results: The positive expression of LAT1 and 4F2c was 80% (118/147) and 58% (86/147) (p<0.01), respectively. The expression of LAT1 was identified as an independent significant marker linked to worse prognosis in patients with CRC, and was correlated with tumor cell proliferation, tumor aggressiveness, and metastasis. Moreover, LAT1 was closely associated with the expression of 4F2hc and phosphorylation of the mTOR pathway. Conclusion: LAT1 is a significant molecular marker used to predict prognosis after surgical resection of CRC patients.Colorectal cancer (CRC) is one of the major neoplasms that cause cancer-related deaths worldwide. When the initial diagnosis of CRC is made in the advanced stage of the disease, systemic chemotherapy is a suitable treatment in addition to palliative surgery when necessary. Despite recent translational research efforts, there is still no established biomarker to predict prognosis after any treatment.We investigated the clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression within tumor specimens from patients with human neoplasms and confirmed that LAT1 is highly expressed in many types of cancers (1-9). We found that the increased expression of LAT1 is a clear negative marker predicting worse outcomes in some human cancers (2,(4)(5)(6)(7). Although LAT1 works as a membrane transporter of neutral amino acids, 4F2hc (CD98) is required for its function (10). The L-type amino acid transporter consists of several subtypes, such as LAT1, LAT2, LAT3, and LAT4 (1, 3, 10). Recent studies have indicated that LAT1 can be used as a specific marker for malignant lesions, LAT2 is expressed in normal tissues, LAT3 is observed in hormone-producing tumors such as prostate cancer, and the role of LAT4 in tumor growth and progression is unknown (11). It has been established that LAT1 is an important molecule in targeted therapy, and the inhibition of LAT1 contributes to the suppression of tumor growth via the mammalian target of rapamycin (mTOR) pathway (8, 9). The protein expression of LAT1 has been clinically proven to be different according to the histological subtype, and its overexpression is closely linked to tumor proliferation, angiogenesis, and metastasis (2-9). Little is known about the prognostic significance of LAT1 expression in patients with CRC; however, Hayase et al. recently reported that LAT1 was highly expressed in 72.4% of CRC patients, and its up-2535
In a surgical operation requiring endoscopy, it is essential to obtain a clear endoscopic view. However, it is often disturbed by the contamination on the lens during the surgery. No device can clean the lens surface simply and completely. Many surgeons are hampered by the impaired view and the distraction by the repeated cleaning of the lens. Therefore, we developed a novel endoscope cleaning device to address this problem. The device was made of 3D-printed rubber-like plastic. It contains a syringe filled with saline and an aspiration system. It would be used intraoperatively to wash the lens surface in a few seconds with rapid flow of water and air. The cleaning ability of the device was evaluated using mayonnaise with adenosine triphosphate (ATP) as a model contaminant. The gauze-wiping maneuver was selected as control. After each maneuver, the clarity of the endoscopic view was evaluated, and residual contaminants were assessed quantitatively with ATP assay. The cleaning device obtained a crisp and clear view and eliminated the contaminant on the lens every time after a single cleaning maneuver. The gauze-wiping maneuver required for the lens to be wiped at least three times to obtain a clear view, and even then, some contaminants remained. Repeated contamination and cleaning using gauze led to accumulation of contaminants on the lens, which resulted in difficulty in cleaning the lens as the operation proceeded. The cleaning device did not show such accumulation. Our novel cleaning device with air and water flow has been shown to wash out the lens contaminants completely and immediately in a simple manner. It is expected to improve the safety and cost-effectiveness of endoscopic surgery.
Ulcerative colitis (UC) is thought to be associated with precancerous lesions that can ultimately lead to colon cancer. Therefore, diagnostic markers for colorectal dysplasia and cancer are urgently needed for patients with UC. Stathmin 1 (STMN1) is a novel cancer biomarker that is also a novel target for treatment in several cancers, including colon cancer. However, few studies have investigated the relationship between STMN1 expression and clinical features in colorectal dysplasia and cancer in patients with UC. The present study examined the clinical significance of STMN1 expression in colorectal dysplasia and cancer with UC. The present study performed an immunohistochemical analysis of 31 clinical colorectal samples from eight patients with colorectal dysplasia and/or cancer to assess the relationships between STMN1 expression and clinicopathological features including mismatch repair protein expression, rate of Ki-67 positivity, differentiation level, TNM stage, and UC duration. STNM1 expression was detected in 95.7% of dysplastic and cancerous lesions, whereas p53, the current diagnostic marker, was not expressed in 39.1% of dysplastic and cancerous lesions. Furthermore, STMN1 expression was associated with a high rate of positivity for Ki-67, a proliferation marker. Our data suggest that STMN1 in the colonic mucosa of UC patients may be useful as an early diagnostic marker of dysplasia and colitic cancer.
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.
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