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The global burden of cervical cancer from low and middle-income groups is increasing at alarming rates with more than half a million women being diagnosed every year. Although the disease is largely preventable when screened and diagnosed in earlier stages, the development of resistance and relapse had resulted in a poor prognosis. Therefore, a comprehensive approach needs to be put forward to understand and develop new preventive and therapeutic strategies to effectively combat cancer. Recently, much attention has been diverted to plant-derivatives for the treatment as they exhibit potent anti-cancer properties and side-effects caused by chemotherapeutic agents can also be prevented. Oleanolic acid and Esculetin are natural compounds known for their anti-cancer properties. Hence, the present study investigates the effect and mechanism of these compounds on cervical carcinoma, using HeLa cells. Posttreatment, it was observed that these compounds inhibited proliferation by both arresting the cells in the sub G1 phase and inducing senescence. Also, a marked reduction in the migration and cell survival was observed, as evidenced by results obtained from wound healing assay and Annexin V-FITC/PI staining. Furthermore, studies on the expression pattern of genes involved in major signaling pathways demonstrated a profound effect of these compounds. Taken together, the results of our study suggest that both Oleanolic acid and esculetin serve as a plausible therapeutic agent.Cadmium (Cd) pollution in agricultural soil has always been a knotty problem, which made it necessary to find the mechanism related to Cd transport in plant. In this study, we found a novel character of the CIPK11 modulating the transport of Cd in Arabidopsis thaliana. Over-expression of CIPK11 (CIPK11OE#1-7, CIPK11OE#8-5) resulted in the increased tolerance to Cd stress, which embodied in higher fresh weight, lower Cd enrichment and reactive oxygen species (ROS) than the wild-type (WT) plants. FG 9041 qRT-PCR results showed a collective down-regulation of the expression of IRT1 and transcription factor genes FIT, bHLH039 in the CIPK11-overexpression plants after Cd stress. Overexpression of CIPK11 significantly increased the expression of ABA marker genes in Arabidopsis after Cd stress. With different concentrations of ABA treatment, the root length differences caused by Cd stress could be recovered. However the transcription levels of FIT and bHLH039 decreased in WT and cipk11 mutant when treated with ABA which indicated that ABA can inhibit the transcription of IRT1 by repressing FIT and bHLH039 expression. Taken together, our results demonstrated that the kinase CIPK11 responses to Cd stress by ABA signaling pathway.

CASC9 and miR-424-5p are closely related with hepatocellular carcinoma (HCC) progression. This study aimed to evaluate the effect of CASC9 involved with miR-424-5p on the development of HCC.

qRT-PCR was performed to determine the mRNA expressions of CASC9 and miR-424-5p in HCC tissues/cells and adjacent normal tissues/human hepatic epithelial cells, and to analyze the relationship of CASC9 with the clinico-pathological characteristics and prognosis of HCC patients. Then, cell proliferation was measured by CCK-8 and

clone formation assays. Apoptosis of HCC cells was measured by flow cytometry. Besides, cell migration and invasion were determined by scratch wound-healing and Transwell assays, respectively. DIANA-LncBase V2 and dual luciferase reporter gene assay were used to verify the targeted relationship between CASC9 and miR-424-5p. Bcl-2, Bax and cleaved caspase-3 expressions were detected by Western blot.

Higher expression of CASC9 was observed in HCC tissues/ cells than in adjacent normal tissues/ human hepatic epithelial cells, and was closely linked to poor prognosis of HCC, tumor size, TNM stage, differentiation degree, lymph node metastasis and alpha-fetoprotein (AFP). link2 Down-regulation of CASC9 decreased the proliferation, invasion and migration of HCC cells while enhancing apoptosis. Besides, CASC9 was negatively correlated with miR-424-5p. MiR-424-5p inhibitor enhanced cell proliferation, invasion and migration while decreasing apoptosis. Interestingly, siRNA-CASC9 partially offset the effects of miR-424-5p inhibitor on HCC cells.

CASC9 promoted proliferation, invasion and migration and inhibited apoptosis in HCC cells by inhibiting miR-424-5p.

CASC9 promoted proliferation, invasion and migration and inhibited apoptosis in HCC cells by inhibiting miR-424-5p.

Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia.

This study included 32 patients with locally advanced oropharyngeal squamous cell carcinoma treated with definitive chemoradiation on an institutional protocol incorporating baseline and early midtreatment DCE-MRI. BV maps of the pharyngeal constrictor muscles (PCM) were created, and BV increases midtreatment were correlated with the following parameters at 3 and 12 months post-RT RT dose, Dynamic Imaging Grade of Swallowing Toxicity swallow score, aspiration frequency, European Organisation for Resetor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient’s subsequent risk of toxicities is warranted to improve personalization of RT planning.

Our results suggest that midtreatment BV increases derived from DCE-MRI are an early predictor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient’s subsequent risk of toxicities is warranted to improve personalization of RT planning.

Glioblastoma (GBM) is a devastating disease. With the current treatment of surgery followed by chemoradiation, outcomes remain poor, with median survival of only 15 months and a 5-year survival rate of 6.8%. A challenge in treating GBM is the heterogeneous integrity of the blood-brain barrier (BBB), which limits the bioavailability of systemic therapies to the brain. There is a growing interest in enhancing drug delivery by opening the BBB with the use of focused ultrasound (FUS). We hypothesize that an FUS-mediated BBB opening can enhance the delivery of etoposide for a therapeutic benefit in GBM.

A murine glioma cell line (Pdgf

, Pten

, P53

) was orthotopically injected into B6(Cg)-Tyrc-2J/J mice to establish the syngeneic GBM model for this study. Animals were treated with FUS and microbubbles to open the BBB to enhance the delivery of systemic etoposide. Magnetic resonance (MR) imaging was used to evaluate the BBB opening and tumor progression. Liquid chromatography tandem mass spectrometry was used to measure etoposide concentrations in the intracranial tumors.

The murine glioma cell line is sensitive to etoposide invitro. MR imaging and passive cavitation detection demonstrate the safe and successful BBB opening with FUS. The combined treatment of an FUS-mediated BBB opening and etoposide decreased tumor growth by 45% and prolonged median overall survival by 6 days an approximately 30% increase. The FUS-mediated BBB opening increased the brain tumor-to-serum ratio of etoposide by 3.5-fold and increased the etoposide concentration in brain tumor tissue by 8-fold compared with treatment without ultrasound.

The current study demonstrates that BBB opening with FUS increases intratumoral delivery of etoposide in the brain, resulting in local control and overall survival benefits.

The current study demonstrates that BBB opening with FUS increases intratumoral delivery of etoposide in the brain, resulting in local control and overall survival benefits.

Postoperative radiation therapy (RT) is a common therapy used for patients with prostate cancer. Although clinical trials have established the safety and efficacy of hypofractionation as a primary therapy, there are limited data in a postoperative setting. We conducted a prospective trial to evaluate the safety and feasibility of postoperative hypofractionated RT to the prostate bed.

In this phase 2 trial, patients submitted to radical prostatectomy were treated with hypofractionated RT to the prostate bed (adjuvant or salvage). The prescribed dose was 51 Gy in 15 fractions (3.4 Gy per fraction), using intensity modulated and image guided radiation therapy techniques. The primary endpoint was the rate of acute genitourinary (GU) grade ≥2 toxicity. Secondary endpoints included acute gastrointestinal (GI) and late GU/GI toxicities, biochemical failure-free survival (BFFS), metastasis-free survival, cancer-specific survival, overall survival, and health-related quality of life.

Of 64 enrolled patients, 61 received radiation therapy (57 salvage and 4 adjuvant radiation therapy). After a median follow-up of 16 months, 11.5% of patients experienced acute grade ≥2 GU symptoms and 13.1% experienced acute grade ≥2 GI symptoms. The late grade ≥2 GU toxicity rate was 8.2%, and 1 patient (1.6%) developed both acute and late grade 3 GU toxicity. The late grade ≥2 GI toxicity rate was 11.5%, and no grade 3 GI adverse events were reported. The short follow-up limits our ability to perform a robust oncologic endpoint assessment; however, the 2-year BFFS, use of subsequent salvage therapy, and the development of metastasis were 95.1%, 0%, and 0%, respectively.

Hypofractionated RT to the prostate bed in 15 treatments was safe, with an acceptable GU and GI toxicity profile. link3 Further study in large, randomized trials is warranted.

Hypofractionated RT to the prostate bed in 15 treatments was safe, with an acceptable GU and GI toxicity profile. Further study in large, randomized trials is warranted.The present study investigates the potential of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water maze (MWM) test was employed on 7th day post-surgery to determine learning and memory. Endothelial dysfunction was assessed in isolated aorta by observing endothelial dependent vasorelaxation and levels of serum nitrite. A battery of biochemical and histopathological estimations was performed. Expression analysis of inflammatory cytokines TNF-α and IL-6 was carried out by RT-PCR. BCCAo produced significant impairment in endothelium dependent vasorelaxation and decrease in serum nitrite levels indicating endothelial dysfunction along with poor performance on MWM represents impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid reactive species and decrease in reduced glutathione levels); increase in brain acetylcholinesterase activity; brain myeloperoxidase activity; brain TNF-α & IL-6 levels, brain TNF-α & IL-6 mRNA expression and brain neutrophil infiltration (as marker of inflammation) were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated BCCAo induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. It may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with BCCAo induced VaD and that TXA2 can be considered as an important therapeutic target for the treatment of VaD.