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Background Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer–nerve interaction. Methods We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor‐κB (NF‐κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans. Results Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY‐specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY‐inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF‐κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa‐specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation‐induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT. Conclusion These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms.

To develop and validate a new tissue-based biomarker that improves prediction of outcomes in localized prostate cancer by quantifying the host response to tumor. We use digital image analysis and machine learning to develop a biomarker of the prostate stroma called quantitative reactive stroma (qRS). qRS is a measure of percentage tumor area with a distinct, reactive stromal architecture. Kaplan Meier analysis was used to determine survival in a large retrospective cohort of radical prostatectomy samples. qRS was validated in two additional, distinct cohorts that include international cases and tissue from both radical prostatectomy and biopsy specimens. In the developmental cohort (Baylor College of Medicine, n=482), patients whose tumor had qRS > 34% had increased risk of prostate cancer-specific death (HR 2.94; p=0.039). This result was replicated in two validation cohorts, where patients with qRS > 34% had increased risk of prostate cancer-specific death (MEDVAMC; n=332; HR 2.64; p=0.02) and also biochemical recurrence (Canary; n=988; HR 1.51; p=0.001). By multivariate analysis, these associations were shown to hold independent predictive value when compared to currently used clinicopathologic factors including Gleason score and PSA. qRS is a new, validated biomarker that predicts prostate cancer death and biochemical recurrence across three distinct cohorts. It measures host-response rather than tumor-based characteristics, and provides information not represented by standard prognostic measurements.

Purpose The purpose of this study was to review the published incidence, etiology, clinical features and management of patients who developed infectious interface keratitis (IIK) following lamellar keratoplasty. Design This study is a systematic literature review. Methods We conducted a systematic review of published Chinese and English report through a PubMed search with the medical subject headings using the following terms: corneal transplantation, keratoplasty, anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), deep lamellar endothelial keratoplasty (DLEK), Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping endothelial keratoplasty (DSEK), Descemet stripping automated endothelial keratoplasty (DSAEK), infectious interface keratitis (IIK), fungal keratitis, and bacterial keratitis. Data collected included patient demographics, surgical technique, clinical signs, treatment, outcomes, and donor rim cultures. A review of the relevant literatures was also undertaken. Results From 2007 to Feb. 2018, we identified 62 cases of IIK following lamellar corneal surgery. The mean age was 26.95 ± 8.80 years with a male/female ratio of 11:8 in DALK/ALK group and 69.65 ± 8.00 years with a male/female ratio of 17:16 in DSAEK/DSEK/DMEK group (no gender information for 10 cases). Of the 62 cases, 46 cases (75.41%) were fungal, 9 cases (14.75%) were bacterial, 2 cases (3.28%) were Actinomyces species, 1 case (1.64%) was acanthamoeba, and 4 cases (6.56%) were indeterminant. The mean onset of symptoms was postoperative day (POD) 49.47 ± 48.56 in DALK/ALK group, and 53 ± 112.01 in EK group, and 62.44 ± 50.07 for the bacterial keratitis, and 51.5 ± 102.42 for fungal keratitis. The mean postoperative follow-up period was 10.10 ± 9.36 months in DALK/ALK group and 12.37 ± 12.28 months in DSAEK/DSEK/DMEK group. Of the total 62 cases, 1 case (1.61%) with a Klebsiella pneumoniae positive donor rim cultures was associated with the same pathogen in the IIK, and 16 cases (25.81%) of fungal positive donor rim cultures were associated with the same pathogen in the IIK. Clinical signs included conjunctival injection, interface opacity, stromal edema for bacterial keratitis, and dense white infiltrates at the interface with endothelial plaques in some cases of fungal keratitis. Medical treatment included topical and oral antimicrobial agents. Surgical interventions included therapeutic keratoplasty. In 15 cases (24.19%), medical management was successful. Of the remaining 47 cases, 8 (12.90%) were managed with a repeat lamellar keratoplasty (LK) and 39 (62.90%) were unresponsive to conservative medical treatment and underwent a therapeutic keratoplasty (TKP). Post infectious best corrected visual acuity (BCVA) was logMAR 0 in 7 eyes (11.29%), better than or equal to logMAR 0.4 in 20 eyes (32.26%), less than logMAR 0.4 in 22 eyes (35.48%) and logMAR 0.7 or worse in 13 eyes (20.97%). In the rim culture negative group(n = 19), the average BCVA was logMAR 0.59 ± 0.68, with was logMAR 0.44 ± 0.74 in rim culture positive group (n = 15). There were three recurrence cases were reported after DMEK during the postoperative follow-up period. Conclusions Infectious interface keratitis (IIK) is an uncommon complication of lamellar keratoplasty, but it can result in a substantial loss of vision or permanent blindness. Although graft infection can occur at any time following surgery, it most commonly (87%) occurred during the first 3 months postoperatively (54/62 cases). The most commonly reported causative organism of IIK following lamellar keratoplasty was C. albicans. Positive rim culture results can provide more rapid and appropriate treatment directed to the identified organism. Therapeutic keratoplasty (TKP) was the most common surgical procedure for the management of IIK. Visual outcomes post TKP are fair with 32.26% (20/62) of patients obtaining LogMAR 0.4 or better.

Context.—The combination of grading and staging is the basis of current standard of care for prediction for most cancers. D. F. Gleason created the current prostate cancer (PCa) grading system. This system has been modified several times. Molecular data have been added. Currently, all grading systems are cancer-cell based.Objective.—To review the literature available on host response measures as reactive stroma grading and stromogenic carcinoma, and their predictive ability for PCa biochemical recurrence and PCa-specific death.Data Sources.—Our own experience has shown that reactive stroma grading and the subsequently binarized system (stromogenic carcinoma) can independently predict biochemical recurrence and/or PCa-specific death, particularly in patients with a Gleason score of 6 or 7. Stromogenic carcinoma has been validated by 4 other independent groups in at least 3 continents.Conclusions.—Broders grading and Dukes staging have been combined to form the most powerful prognostic tools in standard of care. The time has come for us to incorporate measures of host response (stromogenic carcinoma) into the arsenal of elements we use to predict cancer survival, without abandoning what we know works. These data also suggest that our current definition of PCa might need some revision.

Curcumin is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti‑cancer drug in various human cancers. However, the effects of combination treatment of curcumin with gemcitabine or docetaxel on pancreatic cancer remains elusive. In the present study, the combinatory effects of curcumin with either gemcitabine or docetaxel on the proliferation, apoptosis, migration as well as invasion of PC cells were investigated. Calcusyn software was used to determine whether curcumin has is synergistic with gemcitabine or docetaxel. Combination index values from combinational use were all lower than 1, indicating the synergism of curcumin with gemcitabine or docetaxel on PC cells in vitro. EdU assay showed that curcumin could enhance the ability of gemcitabine or docetaxel to inhibit the proliferation of PC cells. Furthermore, the results from transmission electron microscope, DAPI staining experiments and western blot analysis revealed that curcumin may trigger apoptosis of PC cells via PARP/caspase‑3 signaling pathway and reinforced pro‑apoptotic ability of either gemcitabine or docetaxel. In addition, curcumin exhibited marked suppressive ability on metastasis of PC cells by wound healing and matrigel‑transwell assay. Mechanistically, upregulation of TIMP1/TIMP2 with concomitant downregulation of MMP2/MMP9/N‑cadherin proteins may be involved in this process. In conclusion, curcumin showed synergistic anti‑cancer effects with either gemcitabine or docetaxel on PC cells.

Dry Eye Disease (DED) is a very common disorder that can result in severe disability and vision loss. Although the pathogenesis of DED is not fully understood, hyperosmolarity, inflammation, and tear film instability are recognized as hallmarks of DED. Recently, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a class of medication used to treat HIV, have been shown to inhibit inflammation in a mouse model of retinal atrophy. In this study, we investigated whether Zidovudine (AZT) can inhibit human corneal epithelial cell (HCEC) inflammatory responses under hyperosmotic conditions. HCECs were cultured in hyperosmotic media containing AZT. Cell viability, cytokine production, and reactive oxygen species (ROS) production were measured. We found that AZT decreased nuclear factor kappa B (NF-κB) and Interleukin-6 (IL-6) levels, increased Superoxide Dismutase 1 (SOD1) production, decreased ROS production, and increased cell viability. These results support the novel use of AZT in the reduction of ocular surface inflammation and the promotion of corneal health in the context of DED.

Oxidative stress is widely known to be a major contributor in the pathogenesis of dry eye disease (DED). 4-Hydroxynonenal (4-HNE), a well-known byproduct frequently measured as an indicator of oxidative stress-induced lipid peroxidation, has been shown to be elevated in both human and murine corneal DED samples. This study aims to investigate if 4-HNE is responsible for the oxidative stress in human corneal epithelial cells (HCECs) and explores the underlying mechanism by which it confers its effects. SV40-immortalized HCECs were cultured in minimum essential media (MEM) with 1% penicillin/streptomycin and 10% fetal bovine serum. HCECs were exposed to media with or without 4-HNE and cell culture supernatants were collected at 4 and 24 h. Cellular reactive oxygen species (ROS) measurement was performed using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay kit according to the manufacturer’s instructions. Protein levels of antioxidant enzymes copper/zinc superoxide dismutase 1 (SOD1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were analyzed by Western blot. NF-κB activation and expression of IL-6 and IL-8 were measured using an NF-κB p65 Total SimpleStep ELISA Kit and Proteome Profiler Human Cytokine Array Kit. Cell viability was evaluated by LDH cytotoxicity assay. Treatment with 4-HNE decreased cell viability of HCECs. Band intensities corresponding to levels of ROS production showed a significant increase in ROS generation after treatment with 4-HNE. 4-HNE decreased SOD1 levels and upregulated NQO1 expression in HCECs. A significant increase in activation of NF-κB and production of pro-inflammatory cytokines IL-6 and IL-8 was observed after treatment with 4-HNE. Exposure to N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the oxidative effects of 4-HNE on HCECs. 4-HNE induces oxidative stress in corneal epithelial cells by increasing levels of ROS generation and modifying the expression of antioxidant enzyme levels, decreasing cell viability of HCECs in vitro. This study demonstrates a potential pathway by which 4-HNE functions to confer its detrimental effects and provides a new therapeutic target for the treatment of DED.

Inducing tumour-specific adaptive immunity, such as cytotoxic T lymphocyte (CTL) response, can result in promising antitumour effect against several human malignancies, especially in combination with immune checkpoint blockade strategies. However, little is known whether activation of innate immunity can lead to direct tumoricidal effect. Here, we develop a papilloma pseudovirus-based oral immunotherapeutic approach that shows strong tumoricidal effects in the gut, resulting in an almost tripled lifespan of ApcMin/+ mice (an animal model of human intestinal tumorigenesis). Mechanistically, these pseudoviruses activate the NLRP3 and AIM2 inflammasomes, leading to caspase-1-mediated tumour regression that is dependent on neither cytotoxic T lymphocytes nor humoral immune response. Blocking caspase-1 activation abrogated the therapeutic effects of the pseudoviruses. Thus, targeting innate immune sensors in tumours by the pseudoviruses might represent a strategy to treat intestinal tumours., Innate immunity sensors are expressed by both tumour cells and tumour-associated myeloid cells. Here, the authors show that stimulation of the innate immunity response with pseudoviruses in a genetic mouse model of intestinal cancer triggers tumour regression via Caspase-1 activation.

Background The development of multidrug resistance (MDR) is a crucial problem of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Plasmacytoma variant translocation 1 (PVT-1), a long non-coding RNA (lncRNA), was previously found to be increased in gastric cancer patients and regulated the chemotherapy sensitivity in pancreatic cancer cells. However, the role of PVT1 in multidrug resistant Gastric cancer remains largely unexplored. Methods In this study, the mRNA levels of PVT1 in gastric cancer tissues of cisplatin-resistant patients and two kinds of cisplatin-resistant cells BGC823/DDP and SGC7901/DDP were detected by qRT-PCR. The influence of PVT1 knockdown or overexpression on anticancer drug resistance was assessed by measuring the cytotoxicity of cisplatin and the rate of apoptosis detected by CCK-8 assay and flow cytometry, respectively. Further, we investigated the expression levels of MDR1, MRP, mTOR and HIF-1α by qRT-PCR and western blotting. Results PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. In addition, BGC823/DDP and SGC7901/DDP cells transfected with PVT-1 siRNA and treated with cisplatin exhibited significant lower survival rate and high percentage of apoptotic tumor cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1α. Conclusions Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Wogonin is a kind of natural flavonoid compound. According to findings in the latest studies, wogonin shows a wide range of antitumor effects, with the characteristics of multi-pathway, multi-link and multi-target, such as promoting tumor cell apoptosis through ROS or Ca(2+)-mediated signal paths, enhancing tumor cytotoxicity by TNF-α and TRAIL, blocking tumor cell cycle, inhibiting tumor angiogenesis and resisting cancer synergistically with chemotherapeutic drugs. Moreover, Wogonin could enhance body immune function by enhancing immune cell infiltration, regulating the immune cell phenotype and promoting relevant cytokine secretion. In this paper, the authors summarized the advance in studies on wogonin's antitumor and immunomodulatory effects.

To investigate the correlation between the pathogeneses of diarrhea-pre- dominant irritable bowel syndrome (D-IBS) complicated functional dyspepsia (FD) patients of Gan-stagnation Pi-deficiency Syndrome (GSPDS) and symptoms, psychological states, and gastrointestinal hormones.A total of 111 patients with confirmed D-IBS complicated FD of GSPDS were recruited as the treated group by using Rome III standard and Chinese medical syndrome standard. And 30 healthy volunteers were recruited as the control group. The general condition, scoring for digestive symptoms, and the distribution of GSPDS subtype of all subjects were recorded by a questionnaire, and assessed by Symptom Checklist (SCL-90; a software for psychological test developed by Beijing Huicheng Adult Cor- poration). Meanwhile, plasma levels of 5-hydroxytryptamine (5-HT), somatostatin (SS), vasoactive intestinal peptide (VIP), endothelin (ET), interleukin 10 (IL-10), and interleukin 12 (IL-12) were measured in all subjects.(1) The subtype of D-IBS complicated FD of GSPDS was dominant in Pi-qi deficiency type (51/111,45.9%),Pi yang deficiency type (34/111,30.6%), and GSPDS. There was no statistical difference in the scoring of digestive symptoms among the 3 subtypes (P0.05). (2) Compared with the control group, the anxiety factor score and the total score significantly increased in all three subtypes of D-IBS complicated FD of GSPDS, and the depression score of Pi yang deficiency type and Gan-depression type also significantly increased (P0.05, P0.01); the depression score of Gan-depression type was significantly higher than that of the Pi-qi deficiency type (P0.01). Plasma 5-HT levels were obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities, and VIP and IL-10 levels were significantly lower than those in the control group (P0.05). Plasma VIP levels were also obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities (P0.01), and SS levels were significantly lower than those in the control group (P0.05). There was no statistical difference in plasma ET or IL-12 levels in each patient group, when compared with the control group (P0.05). (3) Compared with the.control group, plasma 5-HT levels significantly increased, plasma VIP and IL-10 levels significantly decreased in ach subtype of D-IBS complicated FD patients of GSPDS (P0.05, P0.01), and no significant change of SS, ET, or IL-12 occurred (P0.05). Besides, plasma 5-HT levels were significantly higher in Gan-depression type than in Pi yang deficiency type, VIP levels were lower in Gan-depression type than in Pi-qi deficiency type (all P0.05).Gan stagnation and Pi deficiency were dominant in D-IBS complicated FD patients of GSPDS. Psychological abnormalities, increased plasma 5-HT levels, and decreased plasma VIP levels were closely correlated with Gan stagnation subtype, which provided some reference for looking for objective indicators of Chinese medical syndromes in treating D-IBS complicated FD patients of GSPDS.

Intestinal mucosa is constantly exposed to environmental Ags. Activation of lamina propria (LP) T cells by luminal Ags may lead to the production of inflammatory cytokines and subsequent mucosal inflammation and tissue damage. However, in normal circumstances, LP T cells do not respond to antigenic stimulation. The mechanisms of this unresponsiveness in healthy subjects are not fully understood. In this study, we found by in vivo analysis that, except for T cells in lymph nodules of the mucosa, 15% of LP T cells underwent apoptosis in normal individuals. In contrast, there was a marked reduction in apoptosis of LP T cells in patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and those with specific colitis. Our findings suggest that apoptosis might be a mechanism that turns off mucosal T cell responses to environmental Ags in healthy subjects, and resistance to apoptosis could be an important cause of mucosal immune dysregulation and tissue inflammation in colitis.

The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153 was studied, as well as a microbial model which can be used to mimic metabolism of buflomedil in mammal was established. Experiments were conducted to screen the capabilities of four strains of Cunninghamella species to transform buflomedil, in which C. blakesleana AS 3.153 was selected for a preparative biotransformation. Furthermore, the microbial model was established based on the transformation condition optimization. The parent drug and its metabolites produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass spectrometry method and three metabolites were identified while two of them were new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12-C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the comparison between different species, the microbial transformation of buflomedil by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in human and Beagle dog than that in rat.

Both repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients.A total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated.After the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P0.05), especially in the repaglinide group (P0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group.Repaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in β-cell function and lipid metabolism.

To discover new chemopreventive agents, a drug screening cell model based on reporter gene and antioxidative response element (ARE) has been established.Four repeas of ARE DNA binding conserved sequences were synthesized and cloned into a GFP expression vector. This construct was stably transfected into HepG2 cells in vitro. The cell model was tested with known chemopreventive agents and the effects of resveratrol, protocatechuic aldehyde, ursolic acid and oleanolic acid at different concentration (0, 12.5, 25, 50, 100, 200 micromol x L(-1)) were observed by determining reporter gene GFP activity.The induce level of GFP was regulated by ARE and the dose-dependence in a certain range was observed. The induce level of GFP by resveratrol was significantly increased.The method can be used to screening of chemopreventive agents from Chinese traditional medicine by measurement of luminescent value of expressed GFP in wells of microtiter plate.

Various chemically synthetic anti-angiogenesis agents have serious side effects. The traditional Chinese medicine has attracted considerable attention because of its low toxicity. This study was to explore the inhibitory effects of Scutellaria barbatae D. Don, a kind of traditional Chinese medicinal anti-cancer herb, on tumor angiogenesis, and investigate its mechanism.Matrigel plug and human umbilical vascular endothelial cells (HUVECs) were used to construct in vivo and in vitro models of angiogenesis to assess the effect of Scutellaria barbatae D. Don on angiogenesis. After cultured with Scutellaria barbatae D. Don, the migration of endothelial cells was examined by Transwell chamber; the expression of vascular endothelial growth factor (VEGF) in HeLa cells was detected by enzyme-linked immunosorbent assay (ELISA).Scutellaria barbatae D. Don significantly inhibited angiogenesis in Matrigel; the tube formation number was significantly lower in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (5.6+/-1.1 vs. 9.8+/-1.3, P=0.001; 1.0+/-0.7 vs. 13.4+/-1.1, P0.001). Migrated endothelial cells was significantly fewer in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (19.75+/-2.63 vs. 24.25+/-2.06, P=0.038; 14.00+/-2.58 vs. 26.5+/-4.65, P=0.006). When treated for 24 h and 48 h, the expression of VEGF in HeLa cells was significantly lower in 40% medicated serum group containing Scutellaria barbatae D. Don than in 40% drug-free serum group (138.67+/-9.50 vs. 195.82+/-2.43, P=0.006; 93.84+/-41.11 vs. 193.68+/-18.37, P=0.036).Scutellaria barbatae D. Don could efficiently inhibit angiogenesis in tumor tissue which might relate with inhibition of endothelial cell migration and down-regulation of VEGF in tumor cells.

To clarify the gene type of Orientia tsutsugamushi (Ot) from Shandong province.Nested-polymerase chain reaction (nPCR) was used to identify the gene type of 23 isolated Ot strains, 2 pools of homogenized leptotrombidium (L.) scutellare, 10 blood specimens of scrub typhus patients, and at the same time to compare with the international reference strains Gilliam, Karp, Kato. Sequencing analysis of the Sta56 gene was also used to further identify the precise gene types.Of the 35 samples, 33 had the same products in the amplification of template Ot-DNA. They all belonged to Kawasaki strains endemic in Japan while 2 (FXS4 and LHGM2 strain) belonged to Karp strains. The Sta56 gene sequence homologies to Japan Kawasaki strain of the 2 representative strains (B-16 and FXS2 strain) of the 33 samples were 94.22%, 95.21% respectively, but they were less than 75.87% to other prototype strains; The homologies to Karp strain of FXS4 and LHGM2 strain were 83.03%, 96.45% respectively. B-16 and FXS2 strain were designated as of types strain Japan Kawasaki, FXS4 and LHGM2 as Karp strain.The results indicated that the dominant Ot strains in Shandong Province were similar to Kawasaki strains, but Karp strains also existed.

The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.

To search for possible antitumor promoters, we carried out a primary screening of 20 xanthones isolated from plants of the Guttiferae family, using their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of these xanthones, namely 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)xanthone (8), dulxanthone-B (10) and latisxanthone-C (15), were observed to significantly inhibit the EBV-EA activation. The investigation indicated that 8, 10 and 15 might be valuable antitumor promoters.

Purpose This study aimed to determine the effect of lovastatin on Rho G-protein expression and activation in human trabecular meshwork (TM) cells. Methods Confluent cultures of low-passage (primary) or transformed (GTM3) human TM cells were incubated overnight with vehicle (0.01% ethanol) or activated lovastatin (10 microM). Changes in Rho mRNA, protein content, and activation were quantified by qRT-PCR, immunoblotting, and ELISA, respectively. F-actin organization was determined using Alexa Fluor 488-conjugated phalloidin. Results Low-passage or transformed TM cells treated with lovastatin exhibited marked increases in RhoA and RhoB mRNA and protein content. Actinomycin D prevented lovastatin-dependent increases in RhoB, but not RhoA, protein accumulation. In contrast, cycloheximide prevented lovastatin from increasing both RhoA and RhoB. Supplementation with mevalonate or geranylgeranyl pyrophosphate prevented, whereas inhibition of geranylgeranyl transferase mimicked, the effects of lovastatin on RhoA and RhoB accumulation. The effect of lovastatin was dose dependent, with newly synthesized protein accumulating in the cytosol. The amount of functionally active (GTP-bound) RhoA in cell lysates was significantly reduced by lovastatin. Lovastatin altered the morphology of TM cells by disrupting F-actin organization. Conclusions Lovastatin enhances the accumulation of RhoA and RhoB in human TM cells, in part, by limiting geranylgeranyl isoprenylation of these G-proteins. We propose that post-translational geranylgeranylation serves as a regulator of both RhoA and RhoB protein expression and processing in human TM cells. Increased accumulation of unprenylated forms of RhoA and RhoB may disrupt Rho-dependent regulation of TM cell cytoskeletal organization.