TSGA10 Over Expression Decreases Metastasic and Metabolic Activity by Inhibiting HIF-1 in Breast Cancer Cells.

BACKGROUND AND AIMS: HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis. METHODS: TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured. RESULTS: Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells. CONCLUSION: Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.

Curcumin: hopeful treatment of hemophilic arthropathy via inhibition of inflammation and angiogenesis.

Introduction: Hemophilic arthropathy (HA) is a serious complication among hemophilic patients causing a wide range of morbidity due to the inflammatory reactions followed by repeated episodes of bleeding. This condition has recently been shown to be accompanied by angiogenesis. The cascade starts with iron accumulation leading to an increase in CD68+ and CD11b+ cells responsible for initiating the inflammation.Areas covered: During inflammation, different factors and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α) actively play parts in the pathogenesis of HA and also angiogenesis. It has been demonstrated that different pro-angiogenic and angiogenic factors such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), oxidative stress and matrix metalloproteinases (MMPs) are also important in the pathogenesis of HA. Curcumin is known for its strong anti-inflammatory and anti-angiogenic potentials. This agent is able to inhibit the mentioned inflammatory and angiogenic factors such as IL-1, IL-6, TNF-α, VEGF, MMPs, and HIF-1α. Also, as well as anti-angiogenic and anti-inflammatory activity, curcumin has a strong antioxidant potential and can decrease oxidative stress.Expert opinion: It seems that curcumin could be considered as a possible agent for the treatment of HA through inhibition of inflammation, oxidative stress, and angiogenesis.

Autophagy, cancer and angiogenesis: where is the link?

BACKGROUND: Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions. MAIN BODY: While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells. CONCLUSION: Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.

Association between Parvovirus B19 and anemia in HIV-infected patients.

Background: Human parvovirus B19 (B19V) can cause anemia in some patients, including those with compromised immunity system. There are a few studies on molecular epidemiology of B19V and its association with anemia in Iran. Therefore, the aim of this study was to determine the B19V DNA, IgM, IgG, genotyping, and viral load in HIV patients in different groups of pregnant women, general population, injection drug users (IDU), and Elite controllers. Also, the possible association of B19V with anemia was studied. Methods: In this case-control study, B19V DNA, anti-B19V IgM, anti-B19V IgG, viral load, and hemoglobin level were assessed in 113 HIV positive patients and 72 healthy controls. Also, CD4+ T cell counts and HIV load were measured in the patients' group. All statistical analyses were done using STATA 14.2 software (Stata Corporation, College Station, Texas, USA). P value < 0.05 was considered statistically significant. Results: Among HIV patients, 19 (16.8%) cases had B19V DNA, 3 (2.7%) had B19V IgM, and 7 (6.2%) had B19V IgG. In control group, the prevalence of B19V DNA, IgM, and IgG was 6 (8.33%), 7(9.7%), and 19 (26.4%), respectively. In subpopulations based on transmission routes, general population had the highest B19V IgG and DNA positivity prevalence and viral load level. There was no significant association between B19V antibodies and DNA with anemia. Conclusion: The results demonstrated that B19V infection cannot be considered as a high-risk factor for anemia in adult HIV patients. However, further studies are needed to determine the exact role of B19V infection in HIV patients.

Bevacizumab Inhibits Angiogenic Cytokines in Head and Neck Squamous Cell Carcinoma: From Gene to the Protein.

Background: Head and neck squamous cell carcinoma (HNSCC) is one most prevalent cancers among worldwide. Aim of this study was to evaluate possible effect of bevacizumab, a vascular endothelial growth (VEGF) factor monoclonal antibody on HNSCC cells in vitro to evaluate angiogenic profile changes. Materials and Methods: HNSCC cells were grown and after that different concentrations of bevacizumab were added in order to evaluate cytotoxic concentration using MTT assay. Then after, the cultured cells in presence of different concentration of bevacizumab were evaluated for gene expression of VEGF, matrix metalloprotease-2 (MMP-2) and MMP-9 using real time polymerase chain reaction (PCR). Moreover, the VEGF expression was evaluated by enzyme-linked immunosorbent assay (ELISA). Results: The concentration at which half cells died (IC59) was calculated 1779 µg/mL and at this concentration, VEGF protein secretion was decreased by over one fold. RT-PCR results showed that MMP2, MMP9 and VEGF decreased by 1, 0.6 and 1.1 folds, respectively. Conclusion: It seems that bevacizumab could be considered as a side therapy for patients with HNSCC due to its potential for inhibition of angiogenic related factors, but further complementary studies are necessary.

Hepatitis D virus infection in Kermanshah, west of Iran: seroprevalence and viremic infections.

AIM: This study aimed to determine the seroprevalence and viremic infection of hepatitis delta virus (HDV) in Kermanshah. BACKGROUND: Hepatitis delta is one of the most complex viral infections of liver that along with hepatitis B virus could lead to fulminant hepatitis, progressive chronic hepatitis, cirrhosis, and hepatocellular carcinoma. METHODS: Referrals with positive HBs Ag were included and tested for HDV Ab using ELISA. Seropositives were subsequently evaluated for viremia by assaying HDV RNA and HBV DNA using real-time PCR. Viremia-related variables were also assessed. RESULTS: From 1749 patients included, 30 had positive HDV Ab, which makes HDV seroprevalence 1.7%. Twenty-nine out of 30 seropositives were assayed for viremia. Fourteen cases (48.3%) had positive HDV PCR, 18 (62.1%) had positive HBV DNA. Eight patients (27.6%) had simultaneous replication of HBV and HDV, six (20.7%) only had HDV replication, ten (34.5%) only had HBV replication and five (17.2%) had no replication of either viruses. CONCLUSION: Kermanshah seems to be a low prevalent area in Middle East. Viremic HDV infection was lower compared to Europe and Africa, probably due to genetic variations of the hosts or the differences in genotypes or sub-types of hepatitis B and D viruses.

Effectiveness of platelet-rich plasma therapy in wound healing of pilonidal sinus surgery: A comprehensive systematic review and meta-analysis.

Pilonidal disease (PD) is a chronic situation which may cause pain, discomfort, inflammation, discharges, and inability to do daily routines. Among two main methods of surgery, open healing is preferred by surgeons since it associates with lower risk of recurrence; however, it could complicate the wound condition by delaying the healing process. For this meta-analysis, a search in Medline, Embase, and Scopus was performed in June 2017 with no restrictions placed on the publication date or languages. Then, time to healing was considered as the effect size and all the data from trials were extracted. The heterogeneity and the variation in pooled estimation were assessed using Cochran's Q test and I-squared, respectively. Meta-regression was used to examine the relationship between the effect size and year, studies' sample sizes, proportion of male gender and age with the cause of heterogeneity. From 11 selected articles finally 4 met our inclusion and exclusion criteria with the total number of 484 patients. Using a fixed-effect model, pool effect was detected 0.642 (95% CI: 0.485-0.798). A homogeneity of pooled effect size estimate for the studies was also found (Cochran Q test, p-value = 0.844, I-square = 0.0%). Moreover, results of meta-regression showed no statistically significant association between the effect size and patients' mean age, year of publication, total sample size, and sex proportion (0.51 < p-values < 0.98). Platelet-rich plasma therapy for PD wounds appeared more effective than classic wound dressing.

Inhibition of Angiogenesis: A Novel Effect of Zataria Multiflora.

Background: Angiogenesis, the formation of new blood vessels from preexisting ones, is among the most important physiological and pathological processes that occur in the body. Under pathological conditions such as tumor growth, psoriasis, corneal neovascularization and rheumatoid arthritis, angiogenesis is substantial for the development of the disease. Zataria multiflora is a member of the Labiatae family with a vast range of traditional uses which has been long known and applied in Iran old medicine. The aim of this study was the evaluation of anti-angiogenic potential of Zataria multiflora. Materials and Methods: In this study, human umbilical vein endothelial cells (HUVECs) were isolated from newborn umbilical veins and then cultured for cytotoxicity (LDH test) assay. Regarding LDH results, following tests such as angiogenesis (cytodex-3 micro carrier) and migration (wound healing) tests were designed. Results: The cytotoxicity assays showed no toxicity of Z.multiflora toward HUVECs in the range of 10-450µg/mL of the extract. This extract was also able to inhibit angiogenesis and migration at 200µg/mL. Conclusion: Our data clearly demonstrated an inhibitory effect of Z. multiflora on angiogenesis and migration of HUVECs. Z. multiflora could be introduced as a significant angiogenesis inhibitor for angiogenesis-dependent diseases in further complementary studies.

Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation.

Psoriasis is a chronic skin disease also affecting other sites such as joints. This disease highly depends on inflammation and angiogenesis as well as other pathways. At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis. Cannabinoids are active compounds of Cannabina Sativa inducing their effects through cannabinoid receptors (CBs). JWH-133 is a synthetic cannabinoid with strong anti-angiogenic and anti-inflammatory activities. This agent is able to inhibit HIF-1 α, VEGF, MMPs, bFGF, IL-8, IL-17, and other mentioned cytokines and adhesion molecules both in vivo and in vitro. Altogether, authors suggest using this cannabinoid for treatment of psoriasis due to its potential in suppressing the two main steps of psoriatic pathogenesis. Of course complementary animal studies and human trials are still required.

l-arginine alters the effect of 5-fluorouracil on breast cancer cells in favor of apoptosis.

Chemoresistance in breast cancer is a major obstacle, especially in p53 mutation types. The aim of this study was to evaluate if a combination therapy of l-arginine with 5-fluorouracil (5-FU) can alter the effect of this chemotherapy drug on breast cancer cells. The study was performed on BT-20 and MCF-7 cell lines. The effects of l-arginine alone and in combination with 5-FU were investigated on cell viability, apoptosis and nitric oxide (NO) production. Drugs effects on the cellular energetic metabolism were investigated through the lactate production and glucose-6-phosphate dehydrogenase (G6PD) activity assay. Migration and invasion of treated cells were assessed. Real- time PCR was used for analyzing the changes in the expression level of CXCL12 and CXCR4 as two important genes involved in migration and metastasis of breast cancer cells. l-arginine increased 5-FU effect on BT-20 and MCF-7 cell lines by reducing cell viability and increasing apoptosis and NO production. Lactate production and G6PD activity assays showed that cellular energetic metabolism of both cells was altered in favor of cell death. Moreover, l-arginine decreased the metastatic activity of both cells which was confirmed through migration, invasion and gene expression results performed for both cell lines. However, drugs effect on MCF-7 (p53 wild-type) was greater than that of BT-20 (p53 mutation) in all sets of experiments. Our findings indicated that l-arginine increased the anticancer effect of 5-FU in BT-20 and MCF-7 cell lines. So, combination therapy with l-arginine and 5-FU could be considered as an effective strategy in breast cancer therapy.

Next target of tranilast: inhibition of corneal neovascularization.

Corneal neovascularization (CN) which is associated with angiogenesis and inflammation is seen in different pathological conditions. Among all these situations inflammation and angiogenesis factors such as vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), tumor necrosis factor-α (TNF-α) and other related factors are involved in CN regardless of the etiology. Thus inhibition of these agents that lead to suppression of angiogenesis and inflammation is one the most important strategies to treat CN. Tranilast (TR) is an anti-allergic medicine which has been used in Japan and South Korea in clinic. TR is able to inhibit VEGF, MMP-2 and MMP-9, TNF-α and some other angiogenic and inflammatory factors. According to the anti-angiogenic and anti-inflammatory activity of TR, we hypothesize on the probable efficacy of TR in treating CN. Also topical application of TR in human eye is reported to be safe, so it would be easier to have additional research on therapeutic potential of TR in clinic.