Clinical significance of CD155 expression and correlation with cellular components of tumor microenvironment in gastric adenocarcinoma

IntroductionCD155 is recently emerging as a promising target in malignancies. However, the relationship between CD155 expression and tumor microenvironment (TME) cell infiltration in gastric adenocarcinoma (GAC) has rarely been clarified.MethodsWe measured CD155 expression in specimens of gastric precancerous disease and GAC by immunohistochemistry. The association of CD155 expression with GAC progression and cells infiltration in TME was evaluated through 268 GAC tissues and public dataset analysis.ResultsWe showed that the expression of CD155 was positively correlated with the pathological development of gastric precancerous disease (r = 0.521, P < 0.0001). GAC patients with high CD155 expression had a poorer overall survival (P = 0.033). Moreover, CD155 expression correlated with aggressive clinicopathological features including tumor volume, tumor stage, lymph node involvement, and cell proliferation (P <0.05). Remarkably, CD155 expression positively related to the infiltration of CD68+ macrophages in TME (P = 0.011). Meanwhile, the positive correlation was observed between CD155 and CD31 (P = 0.026). In addition, patients with high CD155 expression combined with low CD3, CD4, CD8, IL-17, IFN-γ or CD19 expression as well as those with high CD155 and α-SMA expression showed significantly worse overall survival (P < 0.05).ConclusionsCD155 may play a pivotal role in the development of GAC through both immunological and non-immunological mechanisms and be expected to become a novel target of immunotherapy in GAC patients

Differentiation of prostate cancer lesions in the Transition Zone by diffusion-weighted MRI

Objective: To differentiate prostate cancer lesions in transition zone by diffusion-weighted-MRI (DW-MRI). Methods: Data from a total of 63 patients who underwent preoperative DWI (b of 0â1000 s/mm2) were prospectively collected and processed by a monoexponential (DWI) model and compared with a biexponential (IVIM) model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analyses were performed by outlining entire-tumor regions of interest (ROIs). These parameters (separately and combined in a logistic regression model) were used to differentiate lesions depending on histopathological analysis of Magnetic Resonance/transrectal Ultrasound (MR/TRUS) fusion-guided biopsy. The diagnostic ability of differentiate the PCa from BHP in TZ was analyzed by ROC regression. Histogram analysis of quantitative parameters and Gleason score were assessed with Spearman correlation. Results: Thirty (30 foci) cases of PCa in PZ and 33 (36 foci) cases of BPH were confirmed by pathology. Mean ADC, median ADC, 10th percentile ADC, 90th percentile ADC, kurtosis and skewness of ADC and mean D values, median D and 90th percentile D differed significantly between PCa and BHP in TZ. The highest classification accuracy was achieved by the mean ADC (0.841) and mean D (0.809). A logistic regression model based on mean ADC and mean D led to an AUC of 0.873, however, the difference is not significant. There were 7 Gleason 6 areas, 9 Gleason 7 areas, 8 Gleason 8 areas, 5 Gleason 9 areas and 2 Gleason 10 areas detected from the 31 prostate cancer areas, the mean Gleason value was(7.5 ± 1.2). The mean ADC and mean D had correlation with Gleason score(r = â0.522 and r = â0.407 respectively, P < 0.05). Conclusion: The diagnosis efficiency of IVIM parameters was not superior to ADC in the diagnosis of PCa in TZ. Moreover, the combination of mean ADC and mean D did not perform better than the parameters alone significantly; It is feasible to stratify the pathological grade of prostate cancer by mean ADC. Keywords: Prostate cancer, Prostate biopsy, DWI, IVIM, MR/TRUS, Transition zon

Primary ectopic meningiomas: Report of 6 cases with emphasis on atypical morphology and exploratory immunohistochemistry

Aims. To investigate the histological and immunohistochemical features of primary ectopic meningiomas (PEMs), especially those of primary ectopic atypical meningiomas (PEAMs). Methods and results. We examined 6 cases of PEM, including 2 PEAM cases, which occurred separately in left nasal cavity, left lower lung, right neck, left orbit, right upper lung, and left upper lung by histological and immunohistochemical analysis. In general, of the 6 PEM cases analyzed, 4 cases exhibited morphology of Grade I, including 1 fibrous, 1 meningothelial, and 2 transitional variant. The remaining 2 cases shared similar atypical morphology of Grade II. The tumors were distributed in sheet-like patterns with loss of architecture of classic meningiomas. Significant hypercellularity, multi-focal necrosis, and thin-walled blood vessels were identified. The mitotic figures were estimated at 6 per 10 high-power fields in one case, and 8 mitotic figures in another. Immunohistochemically, the 6 PEM cases were all positive for Vimentin and EMA, while none showed immunostaining for CKpan, S-100, CD34, STAT6, SMA, Syn or Bcl-2. 4 PEM cases of Grade I were immunoreactive for PR but negative for P53, while the 2 PEAM cases displayed negative staining for PR but positivity for P53. As for Ki-67, the positive staining of 4 Grade I cases was no greater than 2%, while the positive rates of the 2 PEAM cases were 10% and 20%. Conclusions. Our study has expanded cases of PEMs, especially the 2 PEAM cases in rare sites. Our study has also further summarized the pathological features of PEMs, focusing on the histological features of PEAMs, and the immunohistochemical features worthy of further investigation

Regulation of Ion Homeostasis for Enhanced Tumor Radio‐Immunotherapy

Abstract Intra/extracellular ion content affects the growth and metastasis of tumor cells, as well as the efficacy of various antitumor therapies. Herein, a carbonic anhydrase inhibitor (CAI) is loaded onto pH‐responsive calcium carbonate (CaCO3) nanoparticles and then modify theses nanoparticles with liposomes to obtain biocompatible CaCO3/CAI@Lipsome (CCL) for enhance tumor radio‐immunotherapy. CCL can specially decompose in tumor microenvironment, releasing calcium ion (Ca2+) and CAI, as well as increasing the pH value of extracellular fluid. CAI restrains the flow of hydrogen ion (H+) inside and outside the tumor cells, resulting in the reversal of tumor acidic microenvironment and the increase of intracellular H+, both of which can improve the sensitivity of tumor to radiotherapy. Afterward, the increased intracellular H+ together with radiotherapy‐causes reactive oxygen species promotes calcium influx, leading to cellular calcium overload. Moreover, the CCL‐tailored content of H+ and Ca2+ strengthens radiotherapy‐induced immunogenic cell death and dendritic cell maturation, amplifying systemic anti‐tumor adaptive immunity. Meanwhile, macrophages in the CCL‐treated tumors are polarized from pro‐tumor M2 to anti‐tumor M1 under X‐ray exposure, owing to the neutralization of tumor acidic microenvironment and enhances Ca2+ content. Therefore, multi‐directional regulation of the intra/extra tumor cell pH/calcium by simple nano‐preparation would provide a powerful way to improve the efficacy of radio‐immunotherapy

P3H4 Promotes Malignant Progression of Lung Adenocarcinoma via Interaction with EGFR

Lung cancer is associated with the greatest number of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) accounts for 85% of all cases of lung cancer. Despite recent advances in treatment, the 5-year survival rate remains less than 15%. Thus, the diagnostic and therapeutic role of LUAD remain to be further studied. The prolyl 3-hydroxylase family member 4 (P3H4) is involved in various cancers, but little is known about its role in LUAD. Our study demonstrated that the P3H4 gene was upregulated in LUAD. Clinically, the expression of P3H4 was positively correlated with an advanced TNM stage and shorter survival. Functionally, P3H4 plays a significant role in the metastasis and proliferation of LUAD both in vitro and in vivo. Mechanistically, P3H4 might interact with EGFR to regulate the metabolic substances. Our study indicated that P3H4 is a critical gene in the malignant progression of LUAD and represents a potential biomarker and therapeutic target