Stereotactic Body Radiation Therapy for Patients with Heavily Pretreated Liver Metastases and Liver Tumors

We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1–4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10–40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients

Fungal endophyte Phomopsis liquidambari affects nitrogen transformation processes and related microorganisms in the rice rhizosphere

The endophytic fungus Phomopsis liquidambari performs an important ecosystem service by assisting its host with acquiring soil nitrogen (N), but little is known regarding how this fungus influences soil N nutrient properties and microbial communities. In this study, we investigated the impact of P. liquidambari on N dynamics，the abundance and composition of N cycling genes in rhizosphere soil treated with three levels of N (urea). Ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB) and diazotrophs were assayed using quantitative real-time polymerase chain reaction and denaturing gradient gel electrophoresis at four rice growing stages (S0: before planting, S1: tillering stage, S2: grain filling stage, and S3: ripening stage). A significant increase in the available nitrate and ammonium contents was found in the rhizosphere soil of endophyte-infected rice under low N conditions. Moreover, P. liquidambari significantly increased the potential nitrification rates (PNR), affected the abundance and community structure of AOA, AOB and diazotrophs under low N conditions in the S1 and S2 stages. The root exudates were determined due to their important role in rhizosphere interactions. P. liquidambari colonization altered the exudation of organic compounds by rice roots and P. liquidambari increased the concentration of soluble saccharides, total free amino acids and organic acid

A data preprocessing strategy for metabolomics to reduce the mask effect in data analysis

Metabolomics is a booming research field. Its success highly relies on the discovery of differential metabolites by comparing different data sets (for example, patients vs. controls). One of the challenges is that differences of the low abundant metabolites between groups are often masked by the high variation of abundant metabolites -. In order to solve this challenge, a novel data preprocessing strategy consisting of 3 steps was proposed in this study. In step 1, a ‘modified 80%’ rule was used to reduce effect of missing values; in step 2, unit-variance and Pareto scaling methods were used to reduce the mask effect from the abundant metabolites. In step 3, in order to fix the adverse effect of scaling, stability information of the variables deduced from intensity information and the class information, was used to assign suitable weights to the variables. When applying to an LC/MS based metabolomics dataset from chronic hepatitis B patients study and two simulated datasets, the mask effect was found to be partially eliminated and several new low abundant differential metabolites were rescued

SBRT: An opportunity to improve quality of life for oligometastatic prostate cancer?

Objective: Oligometastatic prostate cancer is a limited metastatic disease state in which potential long-term control is still possible with the use of targeted therapies such as surgery or stereotactic body radiation therapy (SBRT). SBRT may as well potentially prolong the time before the initiation of androgen deprivation therapy (ADT) and docetaxel chemotherapy for oligometastatic prostate cancer. The goal of this study is to outline prognostic factors associated with improved outcome with SBRT for metastatic prostate cancer and to quantify the effect of prior systemic treatments such as ADT and docetaxel on survival after SBRT.Methods: Twenty-four prostate cancer patients were treated with SBRT at the Philadelphia CyberKnife Center between August 2007 and April 2014. Retrospective data collection and analysis were performed for these patients on this IRB approved study. Kaplan–Meier methodology was utilized to estimate and visually assess overall survival at the patient level, with comparisons accomplished using the log-rank test. Unadjusted hazard ratios were estimated using Cox proportional hazards regression modeling. Results: An improved median survival was noted for patients with oligometastatic disease defined as 4 or fewer lesions with median survival of greater than 3 years compared with 11 months for polymetastases (p=0.02). The use of docetaxel at some time in follow up either before or after SBRT was associated with decreased survival with median survival of 9 months vs. greater than 3 years (p=0.01). Conclusion: Prognosis was better for men with recurrent prostate cancer treated with SBRT if they had 4 or less metastases (oligometastases) or if docetaxel was not necessary for salvage treatment. The prolonged median overall survival for men with oligometastases in this population of heavily pretreated prostate cancer patients following SBRT may allow for improved quality of life due to a delay of more toxic salvage therapies

Suberoylanilide Hydroxamic Acid, A Histone Deacetylase Inhibitor, Attenuates Postoperative Cognitive Dysfunction in Aging Mice

Postoperative cognitive dysfunction (POCD) is a recognized clinical entity characterized with cognitive deficits after anesthesia and surgery, especially in aged patients. Previous studies have shown that histone acetylation plays a key role in hippocampal synaptic plasticity and memory formation. However, its role in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, attenuates POCD in aging Mice. After exposed to the laparotomy, a surgical procedure involving an incision into abdominal walls to examine the abdominal organs, 16- but not 3-month old male C57BL/6 mice developed obvious cognitive impairments in the test of long-term contextual fear conditioning. Intracerebroventricular (i.c.v.) injection of SAHA at the dose of (20 μg/2 μl) 3 hours before and daily after the laparotomy restored the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels and significantly attenuated the hippocampus-dependent long-term memory impairments in 16-month old mice. SAHA also reduced the expression of cleaved caspase-3, inducible nitric oxide synthase and N-methyl-D-aspartate receptor-calcium/calmodulin dependent kinase II pathway, and increased the expression of brain-derived neurotrophic factor, synapsin 1, and postsynaptic density 95. Taken together, our data suggest that the decrease of histone acetylation contributes to POCD and may serve as a target to improve the neurological outcome of POCD

Functional Identification and Characterization of Genes Cloned from Halophyte Seashore Paspalum Conferring Salinity and Cadmium Tolerance

Salinity-affected and heavy metal-contaminated soils limit the growth of glycophytic plants. Identifying genes responsible for superior tolerance to salinity and heavy metals in halophytes has great potential for use in developing salinity- and Cd-tolerant glycophytes. The objective of this study was to identify salinity- and Cd-tolerance related genes in seashore paspalum (Paspalum vaginatum), a halophytic perennial grass species, using the yeast cDNA expression library screening method. Based on the Gateway-compatible vector system, a high quality entry library was constructed, which contained 9.9×106 clones with an average inserted fragments length of 1.48 kb representing a 100% full-length rate. The yeast expression libraries were screened in a salinity-sensitive and a Cd-sensitive yeast mutant. The screening yielded 32 salinity-tolerant clones harboring 18 salinity-tolerance genes and 20 Cd-tolerant clones, including 5 Cd-tolerance genes. qPCR analysis confirmed that most of the 18 salinity-tolerance and 5 Cd-tolerance genes were up-regulated at the transcript level in response to salinity or Cd stress in seashore paspalum. Functional analysis indicated that salinity-tolerance genes from seashore paspalum could be mainly involved in photosynthetic metabolism, antioxidant systems, protein modification, iron transport, vesicle traffic, and phospholipid biosynthesis. Cd-tolerance genes from seashore paspalum could be associated with regulating pathways involved in phytochelatin synthesis, HSFA4-relsted stress protection, CYP450 complex and sugar metabolism. The 18 salinity-tolerance genes and 5 Cd-tolerance genes could be potentially used as candidate genes for genetic modification of glycophytic grass species to improve salinity and Cd tolerance and for further analysis of molecular mechanisms regulating salinity and Cd tolerance

Transcriptomic analysis of Campylobacter jejuni NCTC 11168 in response to epinephrine and norepinephrine

Upon colonization in the host gastrointestinal tract, the enteric bacterial pathogen Campylobacter jejuni is exposed to a variety of signaling molecules including the catecholamine hormones epinephrine (Epi) and norepinephrine (NE). NE has been observed to stimulate the growth and potentially enhance the pathogenicity of C. jejuni. However, the underlying mechanisms are still largely unknown. In this study, both Epi and NE were also observed to promote C. jejuni growth in MEM-based iron-restricted medium. Adhesion and invasion of Caco-2 cells by C. jejuni were also enhanced upon exposure to Epi or NE. To further examine the effect of Epi or NE on the pathobiology of C. jejuni, transcriptomic profiles were conducted for C. jejuni NCTC 11168 that was cultured in iron-restricted medium supplemented with Epi or NE. Compared to the genes expressed in the absence of the catecholamine hormones, 183 and 156 genes were differentially expressed in C. jejuni NCTC 11168 that was grown in the presence of Epi and NE, respectively. Of these differentially expressed genes, 102 genes were common for both Epi and NE treatments. The genes differentially expressed by Epi or NE are involved in diverse cellular functions including iron uptake, motility, virulence, oxidative stress response, nitrosative stress tolerance, enzyme metabolism, DNA repair and metabolism and ribosomal protein biosynthesis. The transcriptome analysis indicated that Epi and NE have similar effects on the gene expression of C. jejuni, and provided insights into the delicate interaction between C. jejuni and intestinal stress hormones in the host

Effectiveness of an anti-algal compound in eliminating an aquatic unicellular harmful algal Phaeocystis globosa

Phaeocystis globosa blooms can have negative effects on higher trophic levels in the marine ecosystem and consequently influence human activities. Strain KA22, identified as the bacterium Hahella, was isolated from coastal surface water and used to control P. globosa growth. A methanol extract from the bacteral cells showed strong algicidal activity. After purification, the compound showed a similar structure to prodigiosin when identified with Q-Exactive Orbitrap MS and nuclear magnetic resonance spectra. The compound showed algicidal activity against P. globosa with a 50% Lethal Dose (LD50) of 2.24 μg/mL. The prodigiosin was stable under heat and acid environment, and it could be degraded under alkaline environment and natural light condition. The growth rates of strain KA22 was fast in 2216E medium and the content of prodigiosin in this medium was more than 70 μg/mL after 16 h incubation. The compound showed particularly strong algicidal activity against Prorocentrum donghaiense, P. globosa and Heterosigma akashiwo, but having little effect on three other phytoplankton species tested. The results of our research could increase our knowledge on harmful algal bloom control compound and lead to further study on the mechanisms of the lysis effect on harmful algae

Salvage fractionated Stereotactic Radiotherapy (fSRT) with or without chemotherapy and immunotherapy for recurrent Glioblastoma Multiforme: A single institution experience

Background: The current standard of care for salvage treatment of Glioblastoma Multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival. Methods: From 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18 – 35 Gy (median 25) in 3 – 5 fractions via Cyberknife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof. Results: The median overall survival (OS) from date of recurrence was 8 months (2.5 – 61) and 5.3 months (0.6 – 58) from the end of fSRT. The OS at 6 and 12 months was 47% and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49 and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV < 36 cc, Recursive Partitioning Analysis (RPA) < 5, and ECOG (Eastern Cooperative Oncology Group) performance status < 2 were all associated with improved survival (P <0.05). There was no evidence of radionecrosis for any patient.Conclusions: Radiation Therapy Oncology Group (RTOG) 1205 will establish the role of reirradiation for recurrent GBM, however our study suggests that cyberknife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status or long interval from diagnosis

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting

IntroductionSABR provides a superior NSCLC treatment option when compared to conventional radiotherapy for patients deemed inoperable or refusing surgery. This study retrospectively analyzed the rates of tumor control and toxicity following SABR treatment (Cyberknife system) of primary early-stage NSCLC in a community setting.MethodsOne hundred patients were treated between 2007 and 2011. Patients with T3-4 or N1-3 disease, metastasis, recurrent local disease, or a non-lung primary were excluded from analysis. All patients had biopsy proven disease. Staging included CT or FDGPET scan. Median dose was 54Gy (45-60); 18Gy (10-20) per fraction. Median PTV expansion was 8mm (2-10). Median BED was 151.2. Tumors were tracked via Synchrony, X-Sight Lung, or X-Sight Spine. Patients were evaluated for local control, overall survival, and toxicity. All local failures were determined by evaluating post treatment PET/CT.ResultsWith a median follow up of 27.5 months, the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively. Median survival was 2.29 years; actuarial 3- year survival was 37.20%. Grade-3 toxicity was observed in 2% of patients (pneumonia within two months of treatment, n=1; chronic pneumonitis requiring hospital admission, n=1). No patients demonstrated toxicity above Grade-3. Multivariate analysis did not show T-stage as an independent predictor of OS, though it did trend toward significance.ConclusionIn a community-center setting, definitive treatment of NSCLC with SABR for nonsurgical candidates and those who choose to forego surgery result in excellent and comparable rates of local control and toxicity compared to published series from large academic centers