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1.  NOB1 is essential for the survival of RKO colorectal cancer cells 
AIM: To determine the role of NOB1, a regulator of cell survival in yeast, in human colorectal cancer cells.
METHODS: Lentivirus-mediated small interfering RNA (siRNA) was used to inhibit NOB1 expression in RKO human colorectal cancer cells in vitro and in vivo in a mouse xenograft model. The in vitro and in vivo knockdown efficacy was determined using both Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). qRT-PCR was also used to analyze the downstream signals following NOB1 knockdown. Cell growth and colony formation assays were used to determine the effect of NOB1 inhibition on RKO proliferation and their ability to form colonies. Endonuclease activity, as evaluated by terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL), and annexin V staining were used to determine the presence of apoptotic cell death prior to and following NOB1 inhibition. Cell cycle analysis was used to determine the effect of NOB1 inhibition on RKO cell cycle. A cDNA microarray was used to determine global differential gene expression following NOB1 knockdown.
RESULTS: Virus-mediated siRNA inhibition of NOB1 resulted in (1) the down-regulation of NOB1 expression in RKO cells for both the mRNA and protein; (2) inhibition of NOB1 expression both in vitro and in vivo experimental systems; (3) cell growth inhibition via significant induction of cell apoptosis, without alteration of the cell cycle distribution; and (4) a significant decrease in the average weight and volume of xenograft tumors in the NOB1-siRNA group compared to the control scr-siRNA group (P = 0.001, P < 0.05). Significantly more apoptosis was detected within tumors in the NOB1-siRNA group than in the control group. Microarray analysis detected 2336 genes potentially regulated by NOB1. Most of these genes are associated with the WNT, cell proliferation, apoptosis, fibroblast growth factor, and angiogenesis signaling pathways, of which BAX and WNT were validated by qRT-PCR. Among them, 1451 probes, representing 963 unique genes, were upregulated; however, 2308 probes, representing 1373 unique genes, were downregulated.
CONCLUSION: NOB1 gene silencing by lentivirus-mediated RNA interference can inhibit tumor growth by inducing apoptosis of cancerous human colorectal cells.
doi:10.3748/wjg.v21.i3.868
PMCID: PMC4299339  PMID: 25624720
NOB1; Small RNA interference; Apoptosis; Colorectal cancer; BAX; WNT
2.  Four New Sesquiterpenoids from Cultures of the Fungus Phellinidium sulphurascens 
Four new sesquiterpenoids, namely 12-hydroxy-3-oxodrimenol (1), 11-hydroxyacetoxydrim-7-en-3β-ol (2), 2,6-dimethyl-7,10-epoxy-10-hydroxymethyldodeca-2,11-dien-6-ol (3), and 7,10-epoxy-2,6,10-trimethyldodeca-2,11-diene-4,6-diol (4), along with fourteen known compounds, were isolated from the cultures of Phellinidium sulphurascens. The structures of compounds 1–4 were established on the basis of extensive spectroscopic analysis. All of them were evaluated for their cytotoxic activities.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0047-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0047-x
PMCID: PMC4328000  PMID: 25491089
Phellinidium sulphurascens; Drimane; 7,10-Epoxy-2,6,10-trimethyldodeca-2,11-diene
3.  Four New Sesquiterpenoids from Cultures of the Fungus Phellinidium sulphurascens 
Four new sesquiterpenoids, namely 12-hydroxy-3-oxodrimenol (1), 11-hydroxyacetoxydrim-7-en-3β-ol (2), 2,6-dimethyl-7,10-epoxy-10-hydroxymethyldodeca-2,11-dien-6-ol (3), and 7,10-epoxy-2,6,10-trimethyldodeca-2,11-diene-4,6-diol (4), along with fourteen known compounds, were isolated from the cultures of Phellinidium sulphurascens. The structures of compounds 1–4 were established on the basis of extensive spectroscopic analysis. All of them were evaluated for their cytotoxic activities.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0047-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0047-x
PMCID: PMC4328000  PMID: 25491089
Phellinidium sulphurascens; Drimane; 7,10-Epoxy-2,6,10-trimethyldodeca-2,11-diene
4.  Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in mainland China 
Objective
Chronic levodopa (L-dopa) treatment in Parkinson’s disease (PD) is often associated with the development of motor complications, but the corresponding epidemiological data is rare in Chinese PD patients. The present survey was to investigate the prevalence rate of wearing-off (WO) and dyskinesia among the patients with PD in China.
Methods
From May 2012 to October 2012, a 3-step registry survey for wearing off (WO) and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.
Results
There were 1,558 PD patients fulfilling the inclusion criteria. Among them, 1,051 had at least one positive response of 9-item wearing off questionnaire (WOQ-9), 724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists, respectively. The overall prevalence rates of WO and dyskinesia were 46.5% (95% CI 44.0% - 48.9%) and 10.3% (95% CI 8.8% - 11.8%), respectively. The mean score of WOQ-9 for those with WO was 3.8 (SD = 1.8), with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms. Better improvement of motor symptoms (n = 354, 87.8%) and long-term disease control and drug selection (n = 288, 71.5%) were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.
Conclusions
This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from mainland China. WO prevalence rate among Chinese PD patients was in line with, while dyskinesia prevalence rate was lower than previous reports from other Countries.
Electronic supplementary material
The online version of this article (doi:10.1186/2047-9158-3-26) contains supplementary material, which is available to authorized users.
doi:10.1186/2047-9158-3-26
PMCID: PMC4323338  PMID: 25671102
Parkinson’s disease; Wearing-off; Dyskinesia; Epidemiology
5.  Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius 
Two new steroids, 3α,17α,19,20-tetrahydroxy-4α-methylpregn-8-ene (1) and 3α,12α,17α,20-tetrahydroxy-4α-methylpregn-8-ene (2) and three new sesquiterpenoids, 12-hydroxy-α-cadinol (3), 3α,12-dihydroxy-δ-cadinol (4), and 3α,6α-dihydroxyspiroax-4-ene (5), have been isolated from cultures of the fungus Phellinus igniarius. Their structures were characterized based on extensive spectroscopic data. In preliminary in vitro assays, compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0 % and 7.0 % at 3 × 10−4 M, respectively.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0045-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0045-z
PMCID: PMC4327997  PMID: 25432445
Pregnene steroids; Sesquiterpenes; Phellinus igniarius; Cytotoxicity; Vascular-activities
6.  Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius 
Two new steroids, 3α,17α,19,20-tetrahydroxy-4α-methylpregn-8-ene (1) and 3α,12α,17α,20-tetrahydroxy-4α-methylpregn-8-ene (2) and three new sesquiterpenoids, 12-hydroxy-α-cadinol (3), 3α,12-dihydroxy-δ-cadinol (4), and 3α,6α-dihydroxyspiroax-4-ene (5), have been isolated from cultures of the fungus Phellinus igniarius. Their structures were characterized based on extensive spectroscopic data. In preliminary in vitro assays, compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0 % and 7.0 % at 3 × 10−4 M, respectively.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0045-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0045-z
PMCID: PMC4327997  PMID: 25432445
Pregnene steroids; Sesquiterpenes; Phellinus igniarius; Cytotoxicity; Vascular-activities
7.  The Association of the Vanin-1 N131S Variant with Blood Pressure Is Mediated by Endoplasmic Reticulum-Associated Degradation and Loss of Function 
PLoS Genetics  2014;10(9):e1004641.
High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)–rs2272996–in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P = 0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to rapid endoplasmic reticulum-associated degradation (ERAD) as the underlying mechanism for its reduction. Using HEK293 cells stably expressing vanin-1 variants, we showed that N131S vanin-1 was degraded significantly faster than wild type (WT) vanin-1. Consequently, there were only minimal quantities of variant vanin-1 present on the plasma membrane and greatly reduced pantetheinase activity. Application of MG-132, a proteasome inhibitor, resulted in accumulation of ubiquitinated variant protein. A further experiment demonstrated that atenolol and diltiazem, two current drugs for treating hypertension, reduce the vanin-1 protein level. Our study provides strong biological evidence for the association of the identified SNP with BP and suggests that vanin-1 misfolding and degradation are the underlying molecular mechanism.
Author Summary
Hypertension (HTN) or high blood pressure (BP) is common worldwide and a major risk factor for cardiovascular disease and all-cause mortality. Identification of genetic variants of consequence for HTN serves as the molecular basis for its treatment. Using admixture mapping analysis of the Family Blood Pressure Program data, we recently identified that the VNN1 gene (encoding the protein vanin-1), in particular SNP rs2272996 (N131S), was associated with BP in both African Americans and Mexican Americans. Vanin-1 was reported to act as an oxidative stress sensor using its pantetheinase enzyme activity. Because a linkage between oxidative stress and HTN has been hypothesized for many years, vanin-1's pantetheinase activity offers a physiologic rationale for BP regulation. Here, we first replicated the association of rs2272996 with BP in the Continental Origins and Genetic Epidemiology Network (COGENT), which included nearly 30,000 African Americans. We further demonstrated that the N131S mutation in vanin-1 leads to its rapid degradation in cells, resulting in loss of function on the plasma membrane. The loss of function of vanin-1 is associated with reduced BP. Therefore, our results indicate that vanin-1 is a new candidate to be manipulated to ameliorate HTN.
doi:10.1371/journal.pgen.1004641
PMCID: PMC4169380  PMID: 25233454
8.  Potential Use of Sox9 Gene Therapy for Intervertebral Degenerative Disc Disease 
Spine  2003;28(8):755-763.
Study Design
A new recombinant adenoviral vector expressing Sox9, a chondrocyte-specific transcription factor, was tested in a chondroblastic cell line and primary human intervertebral disc cells in vitro. Direct infection of intervertebral disc cells then was assessed in a rabbit model.
Objectives
To deliver a potentially therapeutic viral vector expressing Sox9 to degenerative human and rabbit intervertebral discs cells, and to assess the effect of Sox9 expression on Type 2 collagen production.
Summary of the Background Data
The concentration of competent Type 2 collagen, an essential constituent of the healthy nucleus pulposus, declines with intervertebral disc degeneration. Recent studies suggest that Sox9 upregulates Type 2 collagen production. Interventions that augment Type 2 collagen production by intervertebral disc cells may represent a novel therapeutic method for patients with degenerative disc disease.
Methods
Adenoviral delivery vectors expressing Sox9 and green fluorescent protein were constructed using the AdEasy system. The chondroblastic cell line, HTB-94, and cultured human degenerated intervertebral disc cells were infected with the vectors. Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were performed to document increased Type 2 collagen expression. The AdSox9 virus then was injected directly into the intervertebral discs of three rabbits. After 5 weeks, the injected discs were evaluated histologically.
Results
The AdSox9 virus efficiently transduced HTB-94 cells and degenerated human disc cells. Western blot analysis confirmed increased Sox9 production. Increased Type 2 collagen production was demonstrated in infected HTB-94 and human disc cells using both reverse transcriptase-polymerase chain reaction and immunohistochemical staining. In the rabbit model, cells infected with AdSox9 maintained a chondrocytic phenotype, and the architecture of the nucleus pulposus was preserved over a 5-week study period compared to control discs.
Conclusions
A novel adenoviral vector efficiently increased Sox9 and Type 2 collagen synthesis in cultured chondroblastic cells and human degenerated disc cells. In a rabbit model, sustained Sox9 production preserved the histologic appearance of the nucleus pulposus cells in vivo. These findings suggest a potential role for Sox9 gene therapy in the treatment of human degenerative disc disease.
PMCID: PMC4123440  PMID: 12698117
degenerative disc disease; gene therapy; nucleus pulposus; Sox9; type 2 collagen
9.  CYTOPLASMIC AND/OR NUCLEAR ACCUMULATION OF THE β-CATENIN PROTEIN IS A FREQUENT EVENT IN HUMAN OSTEOSARCOMA 
The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of β-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of β-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for β-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the β-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of β-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating β-catenin signaling in osteosarcoma. In our survival analysis, β-catenin deregulation conferred a hazard ratio of 1.05, indicating that β-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, β-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of β-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.
doi:10.1002/ijc.10719
PMCID: PMC4122310  PMID: 12402302
Wnt signal; β-catenin; osteosarcoma; tumorigenesis; bone tumor
10.  Six New Vibralactone Derivatives from Cultures of the Fungus Boreostereum vibrans 
Abstract
Phytochemical reinvestigation on the cultural broth of Boreostereum vibrans led to the isolation of six new vibralactone derivatives, vibralactone N (1), vibralactone O (2), vibralactone P (3), 10-lactyl vibralactone G (4), (3S*, 4R*)-6-acetoxymethyl-2,2-dimethyl-3,4-dihydro-2H-chromene-3,4-diol (5), vibralactone Q (6). Their structures were elucidated by extensive spectroscopic methods.
Graphical Abstract
.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0029-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0029-z
PMCID: PMC4199947  PMID: 25159894
Boreostereum vibrans; Cultural broth; Vibralactone derivatives
11.  Six New Vibralactone Derivatives from Cultures of the Fungus Boreostereum vibrans 
Abstract
Phytochemical reinvestigation on the cultural broth of Boreostereum vibrans led to the isolation of six new vibralactone derivatives, vibralactone N (1), vibralactone O (2), vibralactone P (3), 10-lactyl vibralactone G (4), (3S*, 4R*)-6-acetoxymethyl-2,2-dimethyl-3,4-dihydro-2H-chromene-3,4-diol (5), vibralactone Q (6). Their structures were elucidated by extensive spectroscopic methods.
Graphical Abstract
.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0029-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0029-z
PMCID: PMC4199947  PMID: 25159894
Boreostereum vibrans; Cultural broth; Vibralactone derivatives
12.  Three New Humulane Sesquiterpenes from Cultures of the Fungus Antrodiella albocinnamomea 
Three new humulane-type sesquiterpenes, antrodols A–C (1–3), were isolated from cultures of the fungus Antrodiella albocinnamomea. Their structures were elucidated on the basis of extensive spectroscopic analysis. Antrodols A–C (1–3) are first examples of humulane-type sesquiterpenes isolated from cultures of higher fungi, and antrodol A (1) was the first report of humulane-type sesquiterpene with a methyl rearranged at C-3. All compounds were evaluated in the enzyme inhibition assay against two protein-tyrosine phosphatases (PTPs): MEG2 and PTP1Bc.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0032-4) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0032-4
PMCID: PMC4111878  PMID: 25089238
Antrodiella albocinnamomea; Humulane-type sesquiterpenes; Protein tyrosine phosphatase inhibitory activity
13.  Three New Humulane Sesquiterpenes from Cultures of the Fungus Antrodiella albocinnamomea 
Three new humulane-type sesquiterpenes, antrodols A–C (1–3), were isolated from cultures of the fungus Antrodiella albocinnamomea. Their structures were elucidated on the basis of extensive spectroscopic analysis. Antrodols A–C (1–3) are first examples of humulane-type sesquiterpenes isolated from cultures of higher fungi, and antrodol A (1) was the first report of humulane-type sesquiterpene with a methyl rearranged at C-3. All compounds were evaluated in the enzyme inhibition assay against two protein-tyrosine phosphatases (PTPs): MEG2 and PTP1Bc.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0032-4) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0032-4
PMCID: PMC4111878  PMID: 25089238
Antrodiella albocinnamomea; Humulane-type sesquiterpenes; Protein tyrosine phosphatase inhibitory activity
14.  CA125 Level Association with Chemotherapy Toxicity and Functional Status in Older Women with Ovarian Cancer 
Objective
Older women with ovarian cancer have increased cancer-related mortality and chemotherapy toxicity. CA125 is a sensitive biomarker for tumor burden. The study evaluates the association between CA125, geriatric assessment (GA), and treatment toxicity.
Methods
This is a secondary subset analysis of patients age ≥65 with ovarian cancer accrued to a multicenter prospective study that developed a predictive toxicity score for older adults with cancer. Clinical and geriatric covariates included sociodemographics, GA (comorbidity, social support, functional, nutritional, psychological, cognitive status), treatment, and labs. Utilizing bivariate analyses, we determined the association of abnormal CA125 (≥35 U/mL) with baseline GA, grade 3–5 toxicity (CTCAE v.3), dose adjustments, and hospitalization. Logistic regression analysis was used to check for potential confounder for association between CA125 and chemotherapy toxicity.
Results
Fifty-one (10%) of 500 patients accrued to the primary study had a diagnosis of ovarian (92%), peritoneal (4%), or fallopian tube (4%) cancer. Median age was 72 (range, 65–86). Forty-six patients (90%) had stage III–IV disease. Twenty-three patients (45%) received first-line chemotherapy, and 34 (67%) received platinum-doublet therapy. Thirty-six (71%) had an abnormal CA125. Grade 3–5 toxicity occurred in 19 patients (37%). Abnormal CA125 was associated with assistance with instrumental activities of daily living (IADL) (p<0.05), lower performance status (p=0.05), grade 3–5 toxicity (p=0.03), non-heme toxicity (p=0.04), and dose reductions (p=0.01). No association between CA125 level and total toxicity score was observed.
Conclusions
Among older women with ovarian cancer, abnormal CA125 was associated with poor pre-treatment functional status and an increased probability of chemotherapy toxicity and dose reduction.
doi:10.1097/IGC.0b013e318299438a
PMCID: PMC3772622  PMID: 23765208
CA125; older women; ovarian cancer; chemotherapy toxicity; functional status
15.  Whole genome sequencing data from pedigrees suggests linkage disequilibrium among rare variants created by population admixture 
BMC Proceedings  2014;8(Suppl 1):S44.
Next-generation sequencing technologies have been designed to discover rare and de novo variants and are an important tool for identifying rare disease variants. Many statistical methods have been developed to test, using next-generation sequencing data, for rare variants that are associated with a trait. However, many of these methods make assumptions that rare variants are in linkage equilibrium in a gene. In this report, we studied whether transmitted or untransmitted haplotypes carry an excess of rare variants using the whole genome sequencing data of 15 large Mexican American pedigrees provided by the Genetic Analysis Workshop 18. We observed that an excess of rare variants are carried on either transmitted or nontransmitted haplotypes from parents to offspring. Further analyses suggest that such nonrandom associations among rare variants can be attributed to population admixture and single-nucleotide variant calling errors. Our results have significant implications for rare variant association studies, especially those conducted in admixed populations.
doi:10.1186/1753-6561-8-S1-S44
PMCID: PMC4143626  PMID: 25519326
16.  Five New Guanacastane-Type Diterpenes from Cultures of the Fungus Psathyrella candolleana 
Five new guanacastane-type diterpenes, named guanacastepenes P–T (1–5), were isolated from cultures of the fungus Psathyrella candolleana. Their structures were elucidated on the basis of extensive spectroscopic methods. All of the compounds were tested for their 11β-hydroxysteroid dehydrogenase (11β-HSD1) inhibitory activity. Compound 3 exhibited inhibitory activity against both human and mouse isozymes of 11β-HSD1 with IC50 values of 6.2 and 13.9 μM, respectively.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0020-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0020-8
PMCID: PMC4050309  PMID: 24955296
Psathyrella candolleana; Psathyrellaceae diterpenes; Guanacastepenes P–T; 11β-HSD1
17.  Five New Guanacastane-Type Diterpenes from Cultures of the Fungus Psathyrella candolleana 
Five new guanacastane-type diterpenes, named guanacastepenes P–T (1–5), were isolated from cultures of the fungus Psathyrella candolleana. Their structures were elucidated on the basis of extensive spectroscopic methods. All of the compounds were tested for their 11β-hydroxysteroid dehydrogenase (11β-HSD1) inhibitory activity. Compound 3 exhibited inhibitory activity against both human and mouse isozymes of 11β-HSD1 with IC50 values of 6.2 and 13.9 μM, respectively.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0020-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0020-8
PMCID: PMC4050309  PMID: 24955296
Psathyrella candolleana; Psathyrellaceae diterpenes; Guanacastepenes P–T; 11β-HSD1
18.  Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus 
Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1–8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (−)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0015-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0015-5
PMCID: PMC4004861  PMID: 24858140
Albatrellus caeruleoporus; Mushroom; Polyporaceae; Farnesylphenols
19.  Nine New Farnesylphenols from the Basidiomycete Albatrellus Caeruleoporus 
Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1–8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (−)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0015-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0015-5
PMCID: PMC4004861  PMID: 24858140
Albatrellus caeruleoporus; Mushroom; Polyporaceae; Farnesylphenols
20.  Toxicity of Bevacizumab in Combination with Chemotherapy in Older Patients 
The Oncologist  2013;18(4):408-414.
Heart disease is more common in those who do not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have higher odds of developing a grade 3–5 toxicity compared with those who receive chemotherapy alone.
Learning Objectives
Compare characteristics of older patients that receive bevacizumab plus chemotherapy to those treated with chemotherapy alone for advanced NSCLC and CRC.Compare outcomes between older patients treated with bevacizumab plus chemotherapy to chemotherapy alone for advanced NSCLC and CRC.Describe toxicities in older patients treated with bevacizumab plus chemotherapy for advanced NSCLC and CRC.
Background.
Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy.
Patients and Methods.
We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and chemotherapy toxicity. We examined differences in characteristics and outcomes of patients with CRC and NSCLC cancers who received bevacizumab with chemotherapy versus chemotherapy alone.
Results.
From a total of 207 patients, 27 (13%) received bevacizumab plus chemotherapy and 180 (87%) received chemotherapy alone. Groups were similar in sociodemographic and cancer characteristics. There were no baseline differences in GA domains except that patients with heart disease were less likely to receive bevacizumab (4% vs. 26%, p = .01). Seventy-eight percent of patients who had bevacizumab had grade 3–5 toxicity compared to only 57% who received chemotherapy alone (p = .06). Patients receiving bevacizumab were more likely to develop grade 3 hypertension than those who received chemotherapy alone (15% vs. 2%, p < .01). In multivariable analysis, factors associated with grade 3 or more toxicity included: bevacizumab (OR: 2.86, p = .04), CRC (OR: 2.54, p < .01), and baseline anemia (OR: 2.58, p = .03).
Conclusion.
Heart disease was more common in those who did not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have a higher odds of developing a grade 3–5 toxicity compared with those who receive chemotherapy alone.
doi:10.1634/theoncologist.2012-0351
PMCID: PMC3639527  PMID: 23576485
Chemotherapy; Geriatric assessment; Bevacizumab; Drug toxicity; Health services for the aged
21.  Lie Symmetry Analysis and Explicit Solutions of the Time Fractional Fifth-Order KdV Equation 
PLoS ONE  2014;9(2):e88336.
In this paper, using the Lie group analysis method, we study the invariance properties of the time fractional fifth-order KdV equation. A systematic research to derive Lie point symmetries to time fractional fifth-order KdV equation is performed. In the sense of point symmetry, all of the vector fields and the symmetry reductions of the fractional fifth-order KdV equation are obtained. At last, by virtue of the sub-equation method, some exact solutions to the fractional fifth-order KdV equation are provided.
doi:10.1371/journal.pone.0088336
PMCID: PMC3921151  PMID: 24523885
22.  Seven New Drimane-Type Sesquiterpenoids from Cultures of Fungus Phellinus tuberculosus 
Abstract
Seven new drimane-type sesquiterpennoids, phellinuins A–G (1–7), together with one known compound 3β,11,12-trihydroxydrimene (8) were isolated from the cultures of mushroom Phellinus tuberculosus. Their structures were elucidated on the basis of NMR and MS spectroscopic data and by comparison with data reported in the literature.
Graphical Abstract
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0002-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0002-x
PMCID: PMC3956979  PMID: 24660133
Phellinus tuberculosus; Drimane-type sesquiterpennoids; Phellinuins A–G
23.  Seven New Drimane-Type Sesquiterpenoids from Cultures of Fungus Phellinus tuberculosus 
Abstract
Seven new drimane-type sesquiterpennoids, phellinuins A–G (1–7), together with one known compound 3β,11,12-trihydroxydrimene (8) were isolated from the cultures of mushroom Phellinus tuberculosus. Their structures were elucidated on the basis of NMR and MS spectroscopic data and by comparison with data reported in the literature.
Graphical Abstract
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-014-0002-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-014-0002-x
PMCID: PMC3956979  PMID: 24660133
Phellinus tuberculosus; Drimane-type sesquiterpennoids; Phellinuins A–G
24.  Sesquiterpenoids and an ergosterol from cultures of the fungus Daedaleopsis tricolor 
Four new bisabolane sesquiterpenoids daedatrins A-D (1–4), a cadinane sesquiterpene 12-hydroxy-α-cadinol (5), and a heptanorergosterane derivative daedatrin G (6) were isolated from cultures of the basidiomycete Daedaleopsis tricolor. Their structures were elucidated by spectroscopic methods including extensive 2D NMR techniques and X-ray crystallography. All the compounds showed no significant activity against five human cancer cell lines.
Electronic Supplementary Material
Supplementary material is available for this article at 10.1007/s13659-013-0065-0 and is accessible for authorized users.
doi:10.1007/s13659-013-0065-0
PMCID: PMC4131599
Daedaleopsis tricolor; sesquiterpenoid; ergosterane
25.  Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173 
BioMed Research International  2013;2013:835859.
Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR = DVS/DVNS, where DVS and DVNS represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Yret) and the retention parameter derived from the impulse response function (fret). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding.
doi:10.1155/2013/835859
PMCID: PMC3780470  PMID: 24083243

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