Interleukin-18 and −10 may be associated with lymph node metastasis in breast cancer

Reports on the expression of interleukin (IL)-10 in breast cancer are rare. The present study investigated the correlation between IL-18 and −10 in breast cancer, and assessed their clinical significance. Breast cancer (n=104) and breast fibroadenoma (n=31) tissues that were surgically removed and pathologically confirmed at Jinan Central Hospital Affiliated to Shandong University (Jinan, China) between November 2016 and January 2019 were collected. The expression of IL-18 and −10 was observed via immunohistochemistry. Breast cancer tissues were positive for IL-18 expression, which was primarily located in the cell membrane and cytoplasm. A significant difference in IL-18 expression was observed between breast cancer and fibroadenoma tissues (75.0 vs. 19.4%; P<0.001). IL-10 was expressed in breast cancer tissues and primarily located in the cytoplasm. Breast cancer tissues showed a significantly higher level of IL-10 expression compared with breast fibroadenoma tissues (78.8 vs. 22.6%; P<0.001). The regions of positive IL-18 and −10 expression were consistent. Tissues with positive expression of IL-18 and/or −10 had a significantly higher rate of lymph node metastasis than those with negative expression (IL-18: 67.9 vs. 42.3%; P=0.035; and IL-10: 67.1 vs. 40.9%; P=0.047). In conclusion, IL-18 is highly expressed in breast cancer and correlates positively with IL-10. Both IL-18 and −10 may correlate positively with lymph node metastasis in breast cancer.     

Exosome-delivered miR-221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer

MicroRNAs (miRNAs) are involved in the progression of many cancers through largely unelucidated mechanisms. The results of our present study identified a gene cluster, miR-221/222, that is constitutively upregulated in serum exosome samples of patients with colorectal carcinoma (CRC) with liver metastasis (LM); this upregulation predicts a poor overall survival rate. Using an in vitro cell coculture model, we demonstrated that CRC exosomes harboring miR-221/222 activate liver hepatocyte growth factor (HGF) by suppressing SPINT1 expression. Importantly, miR-221/222 plays a key role in forming a favorable premetastatic niche (PMN) that leads to the aggressive nature of CRC, which was further shown through in vivo studies. Overall, our results show that exosomal miR-221/222 promotes CRC progression and may serve as a novel prognostic marker and therapeutic target for CRC with LM.     

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma

Pancreatic cancer, one of the most malignant gastrointestinal tumors, is prone to liver metastasis. However, due to the lack of appropriate and comprehensive diagnostic methods, it is difficult to accurately predict the survival outcomes. Therefore, there is a need to identify effective biomarkers, such as UDP-GlcNAc: βGal β-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3), that predict the survival outcome of patients with pancreatic cancer. In the present study, based on data from 171 cases of pancreatic cancer obtained from The Cancer Genome Atlas portal, the differential expression of mRNAs was screened by comparing cancerous tissues with adjacent tissues. Univariate Cox regression analysis demonstrated that B3GNT3 had prognostic capability and could be an independent prognostic factor for pancreatic adenocarcinoma (PAAD). Using the Tumor Immune Estimation Resource tool and Tumor-Immune System Interaction Database, a potential relationship between B3GNT3 expression and immune cell infiltration was identified in pancreatic carcinoma. Furthermore, 177 samples of pancreatic carcinoma were collected and the association of CD68 expression with B3GNT3 was assessed by immunohistochemical staining. B3GNT3 expression was associated with clinical outcomes in pancreatic carcinoma and related to infiltrating levels of immune cells, which indicated that B3GNT3 could be used as an immunotherapy target for PAAD.     

Image-guided Adaptive Radiotherapy for Bladder Cancer

Technological advancement has facilitated patient-specific radiotherapy in bladder cancer. This has been made possible by developments in image-guided radiotherapy (IGRT). Particularly transformative has been the integration of volumetric imaging into the workflow. The ability to visualise the bladder target using cone beam computed tomography and magnetic resonance imaging initially assisted with determining the magnitude of inter- and intra-fraction target change. It has led to greater confidence in ascertaining true anatomy at each fraction. The increased certainty of dose delivered to the bladder has permitted the safe reduction of planning target volume margins. IGRT has therefore improved target coverage with a reduction in integral dose to the surrounding tissue. Use of IGRT to feed back into plan and dose delivery optimisation according to the anatomy of the day has enabled adaptive radiotherapy bladder solutions. Here we undertake a review of the stepwise developments underpinning IGRT and adaptive radiotherapy strategies for external beam bladder cancer radiotherapy. We present the evidence in accordance with the framework for systematic clinical evaluation of technical innovations in radiation oncology (R-IDEAL).     

The variation of cancellous bones at lumbar vertebra,femoral neck,mandibular angle and rib in ovariectomized sheep

This study aimed to compare the variation of cancellous bones at four skeletal sites: lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep. Sixteen adult sheep were randomly divided into two groups: eight sheep were ovariectomized served as experimental group; the other eight untreated sheep were served as control group. Bone mineral density was assessed by dual-energy X-ray absorptiometry on lumbar vertebrae at baseline and twelve months after ovariectomy. After 12 months, lumbar vertebrae L3 and L4, femoral necks, mandibular angles and the fourth ribs were harvested for micro-CT scanning, histological analysis and biomechanical test. The results showed that bone mineral density of lumbar vertebra decreased significantly in twelfth month (p < 0.05). The results of micro-CT showed that the bone volume/total volume decreased by 45.6%, 36.1% 21.3% and 18.7% in lumbar vertebrae, femoral necks, mandibular angles and ribs in experimental group (p < 0.05) respectively. The trabecular number showed the same downtrend (p < 0.05). Histological analysis showed trabecular area/tissue area decreased by 32.1%, 23.2% and 20.7% in lumbar vertebrae, femoral necks and mandibular angles respectively (p < 0.05), but no significant difference in ribs. Specimens elastic modulus from lumbar vertebra, femoral neck and mandibular angle were 952 ± 76 MPa (628 ± 70 MPa), 961 ± 173 MPa (610 ± 72 MPa) and 595 ± 60 MPa (444 ± 31 MPa) in control group (experimental group) respectively. These datum indicated that the sensibility of cancellous bones to oestrogen deficiency in ovariectomized sheep was site-specific on a pattern as follows: lumbar vertebra, femoral neck, mandibular angle and rib.     

Synthesis and biological effects of 2''-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil.

2'-Fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (FEAU) was synthesized, and its biological activities were compared with those of 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU). Earlier studies indicated that both compounds showed potent anti-herpes simplex virus activity, with a 50% effective dose (ED50) of less than 0.25 microM. In the present study the cell growth inhibitory activity of FEAU (ED50, 200 to 2,060 microM) was found to be about 100-fold less than that of FMAU. With an ED50 ranging from 630 to 3,700 microM, FEAU only weakly inhibited thymidine incorporation into DNA, as compared with FMAU with an ED50 of 9 to 28 microM. Following exposure to [2-14C]FEAU (100 microM), 0.48 pmol/10(6) cells per h was incorporated into the DNA of herpes simplex virus type 1-infected Vero cells, whereas no detectable incorporation was found in uninfected Vero cells or L1210 cells. The Ki of FEAU for thymidine kinase purified from human leukemic cells was greater than 150 microM. For herpes simplex virus type 1- and 2-encoded thymidine kinases, the Kis were 0.6 and 0.74 microM, respectively. Both FEAU and FMAU were relatively nontoxic for mice, with a 50% lethal dose of greater than 800 mg/kg per day (four intraperitoneal doses). However, the lethal dose of FEAU for dogs was 100 mg/kg per day (10 intravenous doses), a dose which is 40- to 80-fold greater than the toxic dose of FMAU. These results suggest that FEAU is a worthy candidate for further development as an antiherpetic agent.     

A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods

OBJECTIVES: To characterize the brain activation patterns evoked by manual and electroacupuncture on normal human subjects. DESIGN: We used functional magnetic resonance imaging (fMRI) to investigate the brain regions involved in electroacupuncture and manual acupuncture needle stimulation. A block design was adopted for the study. Each functional run consists of 5 minutes, starting with 1-minute baseline and two 1-minute stimulation, the interval between the two stimuli was 1 minute. Four functional runs were performed on each subject, two runs for electroacupuncture and two runs for manual acupuncture. The order of the two modalities was randomized among subjects. During the experiment, acupuncture needle manipulation was performed at Large Intestine 4 (LI4, Hegu) on the left hand. For each subject, before scanning started, the needle was inserted perpendicular to the skin surface to a depth of approximately 1.0 cm. Electroacupuncture stimulation was delivered using a continuous rectangular wave form (pulse width 30 ms) at a frequency of 3 Hz. For manual acupuncture, the needle was rotated manually clockwise and counterclockwise at a rate of about 180 times per minute (3 Hz). SUBJECTS: Eleven right-handed, normal, healthy volunteer adults, 6 male and 5 female, ages 21-64 participated in the experiment. RESULTS: Results showed that electroacupuncture mainly produced fMRI signal increases in precentral gyrus, postcentral gyrus/inferior parietal lobule, and putamen/insula; in contrast, manual needle manipulation produced prominent decreases of fMRI signals in posterior cingulate, superior temporal gyrus, putamen/insula. CONCLUSION: These results indicate that different brain networks are involved during manual and electroacupuncture stimulation. It suggests that different brain mechanisms may be recruited during manual and electroacupuncture.     

Experimental autoimmune thyroiditis. In vitro cytotoxic effects of T lymphocytes on thyroid monolayers

Effector mechanisms in experimental autoimmune thyroiditis (EAT) were studied in vitro by establishing a cytotoxicity system with thyroid target cells. Lymph node cells (LNC) from popliteal and inguinal lymph nodes were obtained from CBA/J mice (8-10 wk old) 12-18 d after immunization with 120 micrograms mouse thyroglobulin (MTg) in complete Freund's adjuvant (0.2 ml to both hind footpads and thighs) and were cultured with MTg (10-50 micrograms/ml). On day 5 of culture, viable LNC were added to labeled thyroid monolayers and their cytoxicity was assayed after 16 h. Functional thyroid target cells, as reflected by MTg production for up to 9 d, were prepared by adding 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate and 60 microU thyroid-stimulating hormone/ml to the culture medium. On days 5-7, confluent monolayers were labeled with 111In and used as targets. Specific 111In-release ranged from 56 to 85%. The cytotoxic response is MTg specific and H-2 restricted. Pretreatment of thyroid target cells with rabbit antiserum to MTg completely inhibited cytotoxicity. Pretreatment with mouse antiserum to either Kk or Dk products resulted in approximately 50% inhibition, whereas the combined use of both antisera led to total inhibition. No cytotoxicity was observed when control BALB/c thyroid cultures were the target cells. The kinetics of the expansion of Thy-1+ cytotoxic cells by in vitro exposure to MTg were then studied. The cytotoxic response required 5 d to develop and was abolished by treating LNC on day 4 with monoclonal antibody to Lyt-1.1, but not to Lyt-2.1, plus complement. In contrast, by day 5, cytotoxicity was abrogated by similar treatment with antiserum to Lyt-2.1, but not to Lyt-1.1. We conclude that cytotoxic cells derived from MTg-immunized mice are Lyt-2-bearing cells but require the presence of Lyt-1-bearing cells for their generation and/or differentiation.     

Influences of different vasopressors on stroke volume variation and pulse pressure variation

Pulse pressure variation (PPV) and stroke volume variation (SVV) during mechanical ventilation have been shown to be effective parameters to predict preload responsiveness. Although induced hypertension decreases PPV and SVV, the influences of different vasopressors on PPV and SVV are unknown. 94 patients undergoing elective otologic surgery were randomly divided into three groups: Group P (patients were given phenylephrine), Group D (patients were given dopamine), Group E (patients were given ephedrine). When surgery was ongoing and the circulation state was stable, patients were given the vasopressor to increase the systolic arterial pressure (SAP) to the pre-calculated levels: low level, 10 % < ΔSAP ≤ 20 %; medium level, 20 % < ΔSAP ≤ 30 %; high level, 30 % < ΔSAP ≤ 40 %. When invasive arterial pressure reached the target value, PPV, SVV and other parameters were recorded. Dopamine decreased the PPV and SVV more significantly than ephedrine, but less significantly than phenylephrine. The influences of phenylephrine, dopamine and ephedrine on SVV and PPV are different due to their different pharmacological mechanisms.