Strengthening livelihood resilience in upper catchments of dry areas by integrated natural resources management

The Livelihood Resilience project evolved around the hypothesis that better integrated management can improve the livelihoods of poor farming communities and increase the environmental integrity and water productivity of upstream watersheds in dry areas. This hypothesis was tested by researchers from different Iranian research and executive organizations and farming communities in two benchmark research watersheds in upper Karkheh River Basin in Iran, under the guidance of the ICARDA scientists. Participatory technology development, water, soil, erosion, land degradation and vegetation assessments, livelihood, gender and policy analyses, and integrated workshops delivered a set of principles for watershed management in dry areas

Investigation of CTNNB1 gene mutations and expression in hepatocellular carcinoma and cirrhosis in association with hepatitis B virus infection

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc, promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1 showed missense point mutation in exon 3 of CTNNB1, more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4) rather than HBV-related cases (12.7, P = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC. © 2020 The Author(s)

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

Neuroblastoma (NB) remains the critical challenge in pediatric oncology. It has the highest rate of spontaneous regression among all human cancers. Aurora kinase B (AURKB), a crucial regulator of malignant mitosis, is involved in chromosome segregation and cytokinesis. AZD1152-HQPA (Barasertib) is a small selective inhibitor of AURKB activity and currently bears clinical assessment for several malignancies. Studies suggested that microRNAs are involved in the pathobiology and chemoresistance of neuroblastoma. In the present study, we first investigated the restrictive potentials of AZD1152-HQPA on cell viability, colony formation, nucleus morphology, polyploidy, and cell-cycle distribution. We then studied the expressions level of 88 cancer-related miRNAs in untreated and AZD1152-HQPA-treated NB cell line (SK-N-MC) by real-time PCR using miRNA cancer-array system. After normalizing, the fold change of miRNAs was calculated in the AZD1152-HQPA-treated cell as compared to untreated. Our results demonstrate that the inhibition of AURKB by AZD1152-HQPA induced potent antitumor activity, suppressed cell survival, and triggered apoptosis and polyploidy in NB cells. AZD1152-HQPA, at a relevant concentration, modulated a substantial number of cancer-related miRNAs in NB cell. Interestingly, by screening the literature, among the 7 top AZD1152-HQPA-induced upregulated miRNAs (> 3-fold change; P < 0.01), all were potential tumor suppressors associated with cell apoptosis and cycle arrest, as well as inhibition of angiogenesis, invasion, and metastasis, while two downregulated miRNAs were known to have oncogenic function. Taken together, our study showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Targeting of EGFR increase anti-cancer effects of arsenic trioxide: Promising treatment for glioblastoma multiform

Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very limited survival rate. Drug resistance is the main challenges for good prognosis of GBM patients. Arsenic trioxide (ATO) as a multifunctional drug has been investigated for the treatment of several solid tumors. Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism. In this study, we use erlotinib as an EGFR inhibitor to increase the sensitivity of GBM cell lines to ATO treatment. We evaluate the effects of this combination on metabolic activity, viability, cell proliferation, colony formation, cell cycle distribution, migration, oxidative stress and reactive oxygen species production. Our results showed that combination of ATO with erlotinib synergistically reduced metabolic activity, proliferation and colony forming potential in treated GBM cell lines. This combination induced G2/M cell cycle arrest. We also found that wound-healing rate were suppressed only after combination treatment. In addition, apoptotic cell death and reactive oxygen species content significantly increased after combination treatment. The combination of ATO and erlotinib considerably interfere with survival and migration of treated GBM cell lines through cell cycle arrest and reactive oxygen species production. Present study uncovered that EGFR inhibition could overcome the resistance of glioblastoma cells to ATO treatment. © 2017 Elsevier B.V

Targeting of EGFR increase anti-cancer effects of arsenic trioxide: Promising treatment for glioblastoma multiform

Glioblastoma multiform (GBM) accounts for the most common form of primary brain tumors with very limited survival rate. Drug resistance is the main challenges for good prognosis of GBM patients. Arsenic trioxide (ATO) as a multifunctional drug has been investigated for the treatment of several solid tumors. Amplification/overexpression of the epidermal growth factor receptor (EGFR) gene as a signature genetic abnormality of GBM tumors can be a chemoresistance mechanism. In this study, we use erlotinib as an EGFR inhibitor to increase the sensitivity of GBM cell lines to ATO treatment. We evaluate the effects of this combination on metabolic activity, viability, cell proliferation, colony formation, cell cycle distribution, migration, oxidative stress and reactive oxygen species production. Our results showed that combination of ATO with erlotinib synergistically reduced metabolic activity, proliferation and colony forming potential in treated GBM cell lines. This combination induced G2/M cell cycle arrest. We also found that wound-healing rate were suppressed only after combination treatment. In addition, apoptotic cell death and reactive oxygen species content significantly increased after combination treatment. The combination of ATO and erlotinib considerably interfere with survival and migration of treated GBM cell lines through cell cycle arrest and reactive oxygen species production. Present study uncovered that EGFR inhibition could overcome the resistance of glioblastoma cells to ATO treatment. © 2017 Elsevier B.V

Effectiveness of rectal displacement devices in managing prostate motion: a systematic review

Purpose: To determine whether rectal displacement devices (RDDs) have a prostate-stabilizing effect during prostate external beam radiotherapy (EBRT). Methods: A systematic literature search using the PubMed database from January 1, 2000 to December 30th, 2019 was conducted. The effect of RDDs on inter- and intra-fractional prostate displacements was extracted. Results: From 356 articles identified via the PubMed database and hand search, 21 articles were included in the systematic review. There was no randomized study. Twelve studies evaluated the role of the endorectal balloon (ERB) in managing prostate motion. Four studies reported the effect of hydrogel spacer on prostate motion. Four studies examined the effect of the rectal retractor (RR) on intra-fractional prostate motion, and only one study assessed the impact of ProSpare (Nottinghamshire, UK) in reducing prostate motion. Conclusion: Using an ERB significantly reduces intra-fractional prostate motion. This prostate-stabilizing effect of the ERB can translate into reduced planning target volume (PTV) margins and additional rectal dose sparing. Even with an ERB in place, inter-fractional prostate displacements are seen. As a consequence, ERB application does not obviate daily verification; however, this is not a crucial topic because pretreatment imaging is always done nowadays. As compared with ERB, the hydrogel spacer significantly reduces rectal dose and toxicity without influencing prostate immobilization. The RR can increase prostate and rectal inter- and intra-fractional stability without a clear influence on the reduction of rectal toxicity. Finally, it is unclear whether ProSpare is a suitable device reducing prostate motion. Further study will be required to clarify whether the prostate-stabilizing effects of the ERB and RR can result in a safe reduction of PTV margins and further sparing of organs at risks, especially the rectum. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

Blockade of JAK2/STAT3 intensifies the anti-tumor activity of arsenic trioxide in acute myeloid leukemia cells: Novel synergistic mechanism via the mediation of reactive oxygen species

Reactive oxygen species (ROS) are essential mediators of crucial cellular processes including apoptosis, proliferation, survival and cell cycle. Their regulatory role in cancer progression has seen in different human malignancies such as acute myeloid leukemia (AML). AML patients suffer from high resistance of the tumors against routine therapeutics including ATO. ATO enhance reactive oxygen species levels and induce apoptosis and suppresses proliferation in AML cells. However, some pathways such as JAK2/STAT3 ease anti-tumor activity of ATO by reducing reactive oxygen species amount and protecting the cell from apoptosis. In the present study, we use ruxolitinib (potent JAK2 inhibitor) to increase the sensitivity of AML cells to ATO treatment. We test, the effect of this combination on metabolic activity, proliferation, colony formation, cell cycle distribution, apoptosis, oxidative stress and DNA damage. Our results showed that combination of ATO with ruxolitinib synergistically reduced metabolic activity, proliferation and survival of AML cell lines. This combination induced G1/S cell cycle arrest because of reactive oxygen species elevation and GSH reduction. Besides, enhancement of reactive oxygen species increased apoptosis rate in combination samples. We uncovered that the synergistic anti-tumor effect of ATO and ruxolitinib in AML cells mediates via reactive oxygen species elevation and DNA damage. Overall, our results show that the combinatorial therapy of AML cells is more effective than solo-targeted therapy. © 2018 Elsevier B.V