Programmed death 1/programmed death ligand 1 signaling pathway in tumor immunotherapy:An update / 第二军医大学学报

As negative immune regulatory molecules, the inhibitory co-stimulatory molecules programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) play important roles in the adaptive cellular immunity. PD-L1 expressed in tumor cells is involved in regulating T cell activation and differentiation and inhibiting the anti-tumor immune activity of T cell through specific binding with the receptor molecule PD-1 on T cells. Currently, a variety of agents targeting the immune checkpoints of PD-1/PD-L1 have been used in clinic, which have exhibited long-lasting effect in treatment for different types of tumors. In this review, we summed up the molecular structure, expression features, factors influencing upregulation of PD-1/PD-L1, and their roles in promoting tumor growth and escaping from immune system and tumor immunotherapy.

Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glyco-regulation during disturbances in carbohydrate metabolism.</p><p><b>METHODS</b>The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365 +/- 76.5) g) and 24 overweight rats (weighing (714 +/- 83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI, the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted.</p><p><b>RESULTS</b>There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12 +/- 0.78)%) in the hypothalamus within 19.5 - 25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2 +/- 1.5)% vs (4.2 +/- 0.7)% inhibition, t = 2.12, P < 0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21% vs 23%, t = 0.71, P > 0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than those in the control group (22% vs 31%, t = 3.25, P < 0.01).</p><p><b>CONCLUSIONS</b>There is a transient, but significant, decrease in BOLD signal intensity in the hypothalamus following glucose ingestion, which is similar to that observed in humans. The response of the hypothalamus to glucose ingestion was different in overweight and normal weight rats. The percentage of NPY positive cells in obese rats were lower than those in the control group, although this difference was not statistically significant. The percentage of 5-HT positive cells in obese rats was significantly lower than those in the control group.</p>

Differentiation between malignant and benign ovarian tumors by magnetic resonance imaging / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To determine the magnetic resonance (MR) imaging findings of an ovarian mass which are most predictive of malignancy and assess the value of intravenous gadolinium administration in the characterization of an ovarian mass.</p><p><b>METHODS</b>Totally 74 consecutive patients with a clinically or sonographically indeterminate adnexal mass underwent MR imaging, of whom 59 had subsequent surgical resection of 70 adnexal masses. These 59 patients formed the study population. MR imaging studies were prospectively and independently reviewed by a senior and a junior radiologist. The senior radiologist also reevaluated the studies in a blind fashion after a minimum 6 months interval. The sensitivity, specificity, positive predictive value, and negative predictive value of contrast-enhanced and unenhanced MR imaging were evaluated.</p><p><b>RESULTS</b>The most predictive MR imaging findings for malignancy were presence of vegetations in a cystic lesion and presence of necrosis in a solid lesion. The odds ratio was even higher when the ancillary finding of peritoneal metastasis or ascites was present. Contrast media contributed significantly to lesion characterization. Total 70 ovarian masses were detected by contrast-enhanced MR imaging including 37 malignant ovarian masses and 33 benign ovarian masses with 87% (61/70) accuracy, 86% (32/37) sensitivity, 88% (29/33) specificity, 89% (32/36) positive predictive value, and 85% (29/34) negative predictive value, whereas 70 ovarian masses were detected by unenhanced MR imaging with 74% (52/70) accuracy, 73% (27/37) sensitivity, 76% (25/33) specificity, 77% (27/35) positive predictive value, and 71% (25/35) negative predictive value. There were significant differences in accuracy (P < 0.01), sensitivity (P < 0.01), specificity (P < 0.01) between contrast-enhanced and unenhanced MR imaging.</p><p><b>CONCLUSION</b>Contrast-enhanced MR imaging is highly accurate in detection and characterization of complex adnexal masses.</p>

Optimal MR Pulse Sequences for Hepatic Hemangiomas: Comparison of T2-Weighted Turbo-Spin-Echo, T2-Weighted Breath-hold Turbo-Spin-Echo, and T1-Weighted FLASH Dynamic Imaging

PURPOSE: To optimize MR imaging pulse sequences in the imaging of hepatic hemangioma and to evaluate on dynamic MR imaging the enhancing characteristics of the lesions. MATERIALS AND METHODS: Twenty patients with 35 hemangiomas were studied by using Turbo-spin-echo (TSE) sequence (T2-weighted, T2- and heavily T2-weighted breath-hold) and T1-weighted FLASH imaging acquired before, immediately on, and 1, 3 and 5 minutes after injection of a bolus of Gd-DTPA (0.1 mmol/kg). Phased-array multicoil was employed. Images were quantitatively analyzed for lesion-to-liver signal difference to noise ratios (SD/Ns), and lesion-to-liver signal ratios (H/Ls), and qualitatively analyzed for lesion conspicuity. The enhancing characteristics of the hemangiomas were described by measuring the change of signal intensity as a curve in T1-weighted FLASH dynamic imaging. RESULTS: ForT2-weighted images, breath-hold T2-weighted TSE had a slightly higher SD/N than other pulse sequences, but there was no statistical difference in three fast pulse sequences (p=0.211). For lesion conspicuity, heavily T2-weighted breath-hold TSE images was superior to T2-weighted breath-hold or non-breath-hold TSE (H/L, 5.75, 3.81, 2.87, respectively, p<0.05). T2-weighted breath-hold TSE imaging was more effective than T2-weighted TSE imaging in removing lesion blurring or lack of sharpness, and there was a 12-fold decrease in acquisition time (20 sec versus 245 sec). T1-weighted FLASH dynamic images of normal liver showed peak enhancement at less than 1 minute, and of hemangioma at more than 3 minutes; the degree of enhancement for hemangioma decreased after a 3 minute delay. CONCLUSION: T2-weighted breath-hold TSE imaging and Gd-DTPA enhanced FLASH dynamic imaging with 5 minutes delay are sufficient for imaging hepatic hemangiomas.

Optimal MR Pulse Sequences for Hepatic Hemangiomas: Comparison of T2-Weighted Turbo-Spin-Echo, T2-Weighted Breath-hold Turbo-Spin-Echo, and T1-Weighted FLASH Dynamic Imaging

PURPOSE: To optimize MR imaging pulse sequences in the imaging of hepatic hemangioma and to evaluate on dynamic MR imaging the enhancing characteristics of the lesions. MATERIALS AND METHODS: Twenty patients with 35 hemangiomas were studied by using Turbo-spin-echo (TSE) sequence (T2-weighted, T2- and heavily T2-weighted breath-hold) and T1-weighted FLASH imaging acquired before, immediately on, and 1, 3 and 5 minutes after injection of a bolus of Gd-DTPA (0.1 mmol/kg). Phased-array multicoil was employed. Images were quantitatively analyzed for lesion-to-liver signal difference to noise ratios (SD/Ns), and lesion-to-liver signal ratios (H/Ls), and qualitatively analyzed for lesion conspicuity. The enhancing characteristics of the hemangiomas were described by measuring the change of signal intensity as a curve in T1-weighted FLASH dynamic imaging. RESULTS: ForT2-weighted images, breath-hold T2-weighted TSE had a slightly higher SD/N than other pulse sequences, but there was no statistical difference in three fast pulse sequences (p=0.211). For lesion conspicuity, heavily T2-weighted breath-hold TSE images was superior to T2-weighted breath-hold or non-breath-hold TSE (H/L, 5.75, 3.81, 2.87, respectively, p<0.05). T2-weighted breath-hold TSE imaging was more effective than T2-weighted TSE imaging in removing lesion blurring or lack of sharpness, and there was a 12-fold decrease in acquisition time (20 sec versus 245 sec). T1-weighted FLASH dynamic images of normal liver showed peak enhancement at less than 1 minute, and of hemangioma at more than 3 minutes; the degree of enhancement for hemangioma decreased after a 3 minute delay. CONCLUSION: T2-weighted breath-hold TSE imaging and Gd-DTPA enhanced FLASH dynamic imaging with 5 minutes delay are sufficient for imaging hepatic hemangiomas.