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
Anatomical esophageal position may affect the short-term outcomes after minimally invasive esophagectomy (MIE). A previous single-institutional retrospective study suggested that the ...presence of a left-sided esophagus (LSE) made MIE more difficult and increased the incidence of postoperative complications.
Methods
The current study was a multicenter retrospective study of 303 patients with esophageal cancer who underwent MIE at six esophageal cancer high-volume centers in Kyushu, Japan, between April 2011 and August 2016. The patients were divided into the LSE (66 patients) and non-LSE groups (237 patients) based on the esophageal position on computed tomography images obtained with the patients in the supine position.
Results
Univariate analysis showed that patients with LSE were significantly older than those with non-LSE (69 ± 8 vs. 65 ± 9 years;
P
= 0.002), had a significantly greater incidence of cardiovascular comorbidity (65.2% vs. 47.7%;
P
= 0.013), and a significantly longer operating time (612 ± 112 vs. 579 ± 102 min;
P
= 0.025). Logistic regression analysis verified that LSE was an independent risk factor for the incidence of pneumonia (odds ratio 3.3, 95% confidence interval 1.254–8.695;
P
= 0.016).
Conclusions
The presence of a LSE can increase the procedural difficulty of MIE and the incidence of morbidity after MIE. Thus, careful attention must be paid to anatomical esophageal position before performing MIE.
Organoid technology, a novel 3D cell culture system, can reproduce a patient’s cancer and may be a novel immunotherapy experimental model. However, currently no gastric cancer organoid (GCO) models ...in which the organoid and immune cells are in free contact and sufficiently react with each other exist. In this study, we aimed to create a coculture model in which immune cells can move freely and stay in contact with GCOs. We coated the bottom surface of the plate with Matrigel and adhered stem cells to the Matrigel surface, instead of completely embedding them in Matrigel to culture organoids. This method allowed GCOs to grow on the Matrigel surface while maintaining a three-dimensional structure and reproducing the characteristics of the patient’s cancer. We cocultured GCOs and immune cells. Using this model, immune cells could freely move and were in sufficient contact with the cultured GCOs. Our model allowed real-time observation of the immune response and tumor destruction with time. In addition, the GCO killing assay was assessed with natural killer cells from the same patient. This organoid culture model enabled repeated evaluation of the GCO killing assay with various immune cells in vitro. We established a new experimental model that allowed free movement of immune cells and sufficient contact with GCOs. Using this model, it may be possible to predict the effects of immune checkpoint inhibitors in vitro (using GCOs) before administering them to patients.
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•Gastric culture organoids (GCOs) were established using the overlay culture method.•In real time, PBMCs moving freely and destroying GCOs were observed.•Time lapse imaging showed that healthy and patient-derived NK cells destroyed GCOs.•This model can predict the efficiency of immunotherapy before administration.
Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in ...infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.
The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 ...(LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.
Abdominal spacers are useful for maintaining the distance between the target tumors and surrounding tissues, such as the gastrointestinal tract, in patients treated with carbon ion radiotherapy. ...Surgical intervention to remove the spacers is sometimes necessary because of abdominal infections triggered by long-term spacer placement or intestinal perforation. Therefore, spacers that do not require surgical removal and provide effective drainage against abdominal infections are urgently needed. This study aimed to develop a spacer that could be removed non-surgically and one that provides the therapeutic effect of drainage in patients who receive carbon ion radiotherapy for abdominal tumors. A novel fan-shaped spacer was constructed from a film drain that was folded along the trigger line. Simple withdrawal of the trigger line caused the film drain to fold and the holding lines to become free. We performed laparoscopy-assisted insertion with pneumoperitoneum and blind removal of the spacer fourteen times using a porcine model. Saline in the abdominal cavity was effectively aspirated using the spacer. Our novel fan-shaped spacer could be removed safely without surgery and was able to drain fluid effectively from the abdominal cavity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractWith the aim of developing cast-in-place geopolymer mortar hardened under ambient temperature, this study investigated the effects of the composition ratio of fly ash (FA) and ground ...granulated blast furnace slag (GGBFS) and various alkaline liquids on the compressive strength and density of FA-GGBFS-based geopolymer mortar. Test results clearly show that an increase in GGBFS content in FA-GGBFS-based geopolymer mortar increases the compressive strength, and at least 20% replacement of FA with GGBFS by weight can be sufficiently used as cast-in-place geopolymer mortar under ambient temperature conditions. In this study, various alkaline liquids are characterized by the molar ratios of alkaline metal Na-to-H2O and silicon-to-alkaline metal Na, which are referred to as the alkali/water ratio and silicon/alkali ratio, respectively. In each FA-GGBFS binder mixture, there is a linear relation between the compressive strength and alkali/water ratio if the silicon/alkali ratio within a the certain range.
Purpose
The β2-adrenergic receptor (β2AR) is highly expressed in various human cancers. The prognostic significance of its expression in patients with colorectal cancer (CRC) remains unclear. The aim ...of this study was to assess the prognostic role of β2AR expression in patients with surgically resected CRC.
Methods
One hundred and forty-seven patients with surgically resected CRC were examined using immunohistochemistry. The expression of β2AR was assessed in the specimens of resected primary tumors.
Results
β2AR was expressed in 52.3% of the patients’ tumors. β2AR expression was significantly associated with T factor, N factor, and tumor cell proliferation (Ki-67 labeling index). Univariate analysis demonstrated that T factor, N factor, tumor stage, lymphatic permeation, vascular invasion, perineural invasion, β2AR expression, and Ki-67 labeling index were significant prognostic factors for worse disease-free survival (DFS); all but T factor were also significant predictors for worse overall survival (OS). Multivariate analysis confirmed that expression of β2AR was a significant prognostic marker for predicting worse DFS and OS.
Conclusion
β2AR expression was identified as a significant independent prognostic factor in patients with surgically resected CRC.
A novel mixed-valence Cu(I)-Cu(II) coordination polymer with an infinite two-dimensional structure, Cu3(I)Cu(II)Br3(3,5-Dmpip-dtc)2n (3,5-Dmpip-dtc(-) = 3,5-dimethylpiperidine dithiocarbamate), was ...prepared, and its structure was characterized by X-ray diffraction. It shows semiconducting behavior with a relatively small activation energy and high carrier mobility, which were investigated using impedance spectroscopy and flash photolysis time-resolved microwave conductivity measurements, respectively.
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