Publications by authors named "Muhammad Zulfiqar"

34 Publications

Effectiveness of first-line abiraterone versus enzalutamide among patients ≥80 years of age with metastatic castration-resistant prostate cancer: A retrospective propensity score-weighted comparative cohort study.

Eur J Cancer 2021 Jul 12;152:215-222. Epub 2021 Jun 12.

Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background: Metastatic castration-resistant prostate cancer (mCRPC) disproportionately affects the elderly. There is limited data assessing the efficacy and tolerability of abiraterone acetate (AA) versus enzalutamide in this population.

Objective: To compare the clinical efficacy and tolerability of AA versus enzalutamide in patients ≥ 80 years with mCRPC.

Design, Setting And Participants: A retrospective propensity-weighted comparative cohort study of first-line AA versus enzalutamide among patients with mCRPC aged ≥80 years.

Outcome Measurements And Statistical Analysis: Inverse probability treatment weights based on propensity scores were generated to assess the treatment effect of AA versus enzalutamide on time to PSA progression (TTPP), time to progression (TTP) (first of PSA/radiographic/clinical progression) and overall survival using a weighted Cox proportional hazards model. PSA response rate (PSA RR) was compared between groups using Χ.

Results And Limitations: One hundred fifty-three patients received AA, and 125 received enzalutamide. Enzalutamide was associated with higher PSA RR (61.6% vs 43.8%, P < 0.004), and TTP (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.50-0.88, P = 0.01) but not TTPP (HR 0.73, 95% CI 0.53-1.01, P = 0.06). There were significantly more dose reductions with enzalutamide (22.9% vs 44.8%, P > 0.001) but there was no interaction between median proportion of full dose received and TTPP or TTP for either drug. Rates of treatment discontinuation (for reasons other than progression) were also significantly different between AA and enzalutamide (28.8% vs 40.8%, respectively, P = 0.04). The most common reason for dose reductions and discontinuation of enzalutamide was fatigue (30.4% and 5.6%, respectively).

Conclusions: Despite more dose reductions and a higher treatment discontinuation rate, enzalutamide was associated with a higher PSA RR and longer time to progression, than AA. Given that clinical outcomes were not adversely impacted by decreased treatment exposure, dose modification may be a useful treatment strategy to balance toxicity and tolerance.
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http://dx.doi.org/10.1016/j.ejca.2021.05.003DOI Listing
July 2021

Evolution of Castration-Resistant Prostate Cancer in CtDNA during Sequential Androgen Receptor Pathway Inhibition.

Clin Cancer Res 2021 Jun 3. Epub 2021 Jun 3.

Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, British Columbia, Canada.

Purpose: Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance.

Experimental Design: We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357). We utilized deep targeted and whole-exome sequencing to compare baseline and posttreatment somatic genomic profiles in circulating tumor DNA (ctDNA).

Results: Patient ctDNA abundance was correlated across plasma collections and independently prognostic for sequential therapy response and overall survival. Most driver alterations in established prostate cancer genes were consistently detected in ctDNA over time. However, shifts in somatic populations after treatment were identified in 53% of patients, particularly after strong treatment responses. Treatment-associated changes converged upon the gene, with an average 50% increase in copy number, changes in mutation frequencies, and a 2.5-fold increase in the proportion of patients carrying AR ligand binding domain truncating rearrangements.

Conclusion: Our data show that the dominant genotype continues to evolve during sequential lines of AR inhibition and drives acquired resistance in patients with mCRPC.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1625DOI Listing
June 2021

Behavior Towards R&D Investment of Family Firms CEOs: The Role of Psychological Attribute.

Psychol Res Behav Manag 2021 26;14:595-620. Epub 2021 May 26.

School of Business Administration, Dongbei University of Finance and Economics, Dalian, People's Republic of China.

Introduction: This study aims to explore the effects of the behavior of chief executive officers (CEOs) within family firms on investment in research and development (R&D). We also investigate the effect of CEOs' psychological attributes of overconfidence on R&D investment and the moderating effect between the types of CEOs and R&D investment.

Methods: We obtained data on Chinese A-share firms from China Stock Exchange and Accounting Research from 2010 to 2018 for analysis. Then, we used the ordinary least squares model for regression results; moreover, the Tobit regression, GMM and firm fixed effect model are applied to check the robustness of the results.

Results: Family CEOs with actual control rights are more open to R&D investment, whereas those without actual control rights exhibit negative behavior. The study found that non-family CEOs exhibit insignificant results and negative predicted signs toward R&D investment. Moreover, the results show that overconfident CEOs are more inclined to amplify innovation. Furthermore, results on the moderating effects of CEO psychological attribute of overconfidence indicate that the CEO overconfidence mitigates the negative relationship between family CEOs with actual control rights and R&D investment. However, no moderating effect is found between family CEOs without actual control and R&D investment. The CEO psychological attribute behavior is positive between non-family CEOs and R&D investment.

Discussion: This novel study explores the behavioral effect of different types of family firm CEOs on R&D investment. This study will assist corporate board members to make more informed decisions about retaining (or bringing back) family CEOs (with or without actual control rights) or hiring non-family CEOs.
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http://dx.doi.org/10.2147/PRBM.S306443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167369PMC
May 2021

Regional disparities in Preventive measures of COVID-19 pandemic in China. A study from international students' prior knowledge, perception and vulnerabilities.

Environ Sci Pollut Res Int 2020 Oct 10. Epub 2020 Oct 10.

School of Economics and Management, Nanjing University of Science and Technology, Nanjing, 210094, People's Republic of China.

The COVID-19 pandemic needs immediate solution before inflicting more devastation. So far, China has successfully controlled transmission of COVID-19 through implementing stringent preventive measures. In this study, we analyze the effectiveness of preventive measures taken in thirteen regions of China based on the feedback provided by 1135 international students studying in China. The study uses factor analysis combined with varimax rotation of variables. It was found that awareness raising and dispersing actionable knowledge regarding trust and adapting measures remained significantly important. Therefore, recognition of information gaps, improvements in the level of alertness, and development of preventive measures in each sector are imperative. The findings of this study revealed that trust, students' health, waste disposal, and the efforts of the Chinese government/international institute of education to prevent this pandemic were significantly and positively associated with preventive measures. The results showed that prior knowledge, global pandemics, and food and grocery purchases were firmly related to the preventive measures of COVID-19. Moreover, anxiety, transportation, and economic status were negatively related to the preventive measures. During this epidemic situation, international students suffered various types of mental stresses and anxiety, especially living in most affected regions of China. The study adopted a mixed (qualitative and quantitative) approach where the findings can act as a set of guidelines for governmental authorities in formulating, assisting in the preparation, instructing, and guiding policies to prevent and control the epidemic COVID-19 at national, local, and divisional levels.
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http://dx.doi.org/10.1007/s11356-020-10932-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547302PMC
October 2020

Response surface methodology and artificial neural network for remediation of acid orange 7 using TiO-P25: optimization and modeling approach.

Environ Sci Pollut Res Int 2020 Sep 15;27(27):34018-34036. Epub 2020 Jun 15.

Department of Chemical Engineering, Universiti Teknologi PETRONAS, 32610, Bandar Sri Iskandar, Perak, Malaysia.

The primary responsibility for continuously discharging toxic organic pollutants into water bodies and open environments is the increase in industrial and agricultural activities. Developing economical and suitable methods to continuously remove organic pollutants from wastewater is highly essential. The aim of the present research was to apply response surface methodology (RSM) and artificial neural networks (ANNs) for optimization and modeling of photocatalytic degradation of acid orange 7 (AO7) by commercial TiO-P25 nanoparticles (TNPs). Dose of TNPs, pH, and AO7 concentration were selected as investigated parameters. RSM results reveal the reflective rate of AO7 removal of ~ 94.974% was obtained at pH 7.599, TNP dose of 0.748 g/L, and AO7 concentration of 28.483 mg/L. The resulting quadratic model is satisfactory with the highest coefficient of determination (R) between the predicted and experimental data (R = 0.98 and adjusted R = 0.954). On the other hand, ANNs were successfully employed for modeling of AO7 degradation process. The proposed ANN model was absolutely fitted with experimental results producing the highest R. Furthermore, root mean square error (RMSE), mean average deviation (MAD), absolute average relative error (AARE), and mean square error (MSE) were examined more to compare the predictive capabilities of ANN and RSM models. The experimental data was well fitted into pseudo-first-order and pseudo-second-order kinetics with more accuracy. Thermodynamic parameters, namely enthalpy, entropy, Gibbs' free energy, and activation energy, were also evaluated to suggest the nature of the degradation process. The increase of temperature was analyzed to be more suitable for the fast removal of AO7 over TNPs. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-020-09674-4DOI Listing
September 2020

Signifying the imperative nexus between climate change and information and communication technology development: a case from Pakistan.

Environ Sci Pollut Res Int 2020 Aug 28;27(24):30502-30517. Epub 2020 May 28.

School of Accounting, Dongbei University of Finance and Economics, Dalian, China.

The globe has faced technological affluence that enormously revolutionized the lives of humankind. Today, the manufacturing process of the energy sector, production sector, agriculture sector, and service sector is exclusively or partially based on ICT tools. The key intention of this investigation is to find out the impacts of the utilization of ICT on CO emission. However, this investigation also evaluates the influence of investment in ICT and the trade of ICT tools on CO emission. Further, the estimation examined the subsistence of environment Kuznets curve (EKC) theory, for the nation of Pakistan. The investigation employed an autoregressive distributed lag (ARDL) model and found that the utilization of ICT has a negative impact on CO emission. Moreover, the long-run results revealed that the import of ICT equipment is more beneficial for the environment quality of Pakistan. However, ICT apparatus manufactured in Pakistan might produce electronic waste due to non-utilization of green technology. The study reported bidirectional causality between ICT and CO emission. These results point towards that the emergence of ICT in industries and daily life possesses a significant and positive role in climate change in Pakistan. Also, this study corroborates the veracity of EKC in Pakistan.
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http://dx.doi.org/10.1007/s11356-020-09128-xDOI Listing
August 2020

Targeted drug delivery systems: synthesis and in vitro bioactivity and apoptosis studies of gemcitabine-carbon dot conjugates.

Biomed Mater 2020 09 26;15(6):065004. Epub 2020 Sep 26.

Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan.

Gemcitabine (GEM) is used to treat various cancers such as breast, pancreatic, non-small lung, ovarian, bladder, and cervical cancers. GEM, however, has the problem of non-selectivity. Water-soluble, fluorescent, and mono-dispersed carbon dots (CDs) were fabricated by ultrasonication of sucrose. The CDs were further conjugated with GEM through amide linkage. The physical and morphological properties of these carbon dot-gemcitabine (CD-GEM) conjugates were determined using different analytical techniques. In vitro cytotoxicity and apoptosis studies of CD-GEM conjugates were evaluated by various bioactivity assays on human cell lines, MCF-7 (human breast adenocarcinoma), and HeLa (cervical cancer) cell lines. The results of kinetic studies have shown a maximum drug loading efficacy of 17.0 mg of GEM per 50.0 mg of CDs. The CDs were found biocompatible, and the CD-GEM conjugates exhibited excellent bioactivity and exerted potent cytotoxicity against tumor cells with an IC value of 19.50 μg ml in HeLa cells, which is lower than the IC value of pure GEM (∼20.10 μg ml). In vitro studies on CD-GEM conjugates demonstrated the potential to replace the conventional administration of GEM. CD-GEM conjugates are more stable, have a higher aqueous solubility, and are more cytotoxic as compared to GEM alone. The CD-GEM conjugates show reduced side effects in the normal cells along with excellent cellular uptake. Hence, CD-GEM conjugates are more selective toward cancerous cell lines as compared to non-cancerous cells. Also, the CD-GEM conjugates successfully induced early and late apoptosis in cancer cell lines and might be effective and safe to use for in vivo applications.
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http://dx.doi.org/10.1088/1748-605X/ab95e1DOI Listing
September 2020

Efficient Removal of Pb(II) from Aqueous Solutions by Using Oil Palm Bio-Waste/MWCNTs Reinforced PVA Hydrogel Composites: Kinetic, Isotherm and Thermodynamic Modeling.

Polymers (Basel) 2020 Feb 12;12(2). Epub 2020 Feb 12.

Chemical Engineering Department, Universiti Teknologi PETRONAS, Seri Iskandar 32610, Perak Darul Ridzuan, Malaysia.

Polyvinyl alcohol (PVA) hydrogel are still restricted for some applications because their lower mechanical strength and thermal stability. The PVA-based composites are drawing attention for the removal of heavy metals based on their specific functionality in adsorption process. The main objective of this work is to synthesize oil palm bio-waste (OPB)/multiwalled carbon nanotubes (MWCNTs) reinforced PVA hydrogels in the presence of ,'-methylenebisacrylamide (NMBA) as a crosslinking agent and ammonium persulfate (APS) as an initiator via simple in-situ polymerization technique. The as-prepared reinforced nanocomposites were characterized by FESEM, BET surface area, differential scanning calorimetry (DSC), TGA and FTIR analysis. The possible influence of OPB and MWCNTs on the tensile strength, elongation at break and elastic modulus of the samples were investigated. It was found that reinforced nanocomposites exhibited enhanced mechanical properties as compared to non-reinforced material. The evaluation of reinforced nanocomposites was tested by the removal of Pb(II) aqueous solutions in a batch adsorption system. The pseudo-second-order kinetic model was used to illustrate the adsorption kinetic results and Langmuir isotherm was more suitable to fit the equilibrium results providing maximum adsorption capacities. The evaluation of thermodynamic parameters describes the spontaneous, endothermic and chemisorption adsorption process while activation energy reveals the physical adsorption mechanism. Therefore, the coordination effects among OPB, MWCNTs and PVA polymer hydrogels can produce a promising adsorbent material for wastewater treatment applications.
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http://dx.doi.org/10.3390/polym12020430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077652PMC
February 2020

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial.

Lancet Oncol 2019 12 11;20(12):1730-1739. Epub 2019 Nov 11.

Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada. Electronic address:

Background: Abiraterone acetate plus prednisone and enzalutamide are both used for the treatment of metastatic castration-resistant prostate cancer. We aimed to determine the best sequence in which to use both drugs, as well as their second-line efficacy.

Methods: In this multicentre, randomised, open-label, phase 2, crossover trial done in six cancer centres in British Columbia, Canada, we recruited patients aged 18 years or older with newly-diagnosed metastatic castration-resistant prostate cancer without neuroendocrine differentiation and Eastern Cooperative Oncology Group performance status 2 or less. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily until PSA progression followed by crossover to enzalutamide 160 mg orally once daily (group A), or the opposite sequence (group B). Treatment was not masked to investigators or participants. Primary endpoints were time to second PSA progression and PSA response (≥30% decline from baseline) on second-line therapy, analysed by intention-to-treat in all randomly assigned patients and in patients who crossed over, respectively. The trial is registered with ClinicalTrials.gov, NCT02125357.

Findings: Between Oct 21, 2014, and Dec 13, 2016, 202 patients were enrolled and randomly assigned to either group A (n=101) or group B (n=101). At the time of data cutoff, 73 (72%) patients in group A and 75 (74%) patients in group B had crossed over. Time to second PSA progression was longer in group A than in group B (median 19·3 months [95% CI 16·0-30·5] vs 15·2 months [95% CI 11·9-19·8] months; hazard ratio 0·66, 95% CI 0·45-0·97, p=0·036), at a median follow-up of 22·8 months (IQR 10·3-33·4). PSA responses to second-line therapy were seen in 26 (36%) of 73 patients for enzalutamide and three (4%) of 75 for abiraterone (χ p<0·0001). The most common grade 3-4 adverse events throughout the trial were hypertension (27 [27%] of 101 patients in group A vs 18 [18%] of 101 patients in group B) and fatigue (six [10%] vs four [4%]). Serious adverse events were reported in 15 (15%) of 101 patients in group A and 20 (20%) of 101 patients in group B. There were no treatment-related deaths.

Interpretation: Enzalutamide showed activity as a second-line novel androgen receptor pathway inhibitor, whereas abiraterone acetate did not, leading to a longer time to second PSA progression for the sequence of abiraterone followed by enzalutamide than with the opposite treatment sequence. Our data suggest that using a sequencing strategy of abiraterone acetate followed by enzalutamide provides the greatest clinical benefit.

Funding: Canadian Cancer Society Research Institute, Prostate Cancer Canada, Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program, BC Cancer Foundation, Jane and Aatos Erkko Foundation, Janssen, and Astellas.
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http://dx.doi.org/10.1016/S1470-2045(19)30688-6DOI Listing
December 2019

Intrinsic Thermal conductivities of monolayer transition metal dichalcogenides MX (M = Mo, W; X = S, Se, Te).

Sci Rep 2019 Mar 14;9(1):4571. Epub 2019 Mar 14.

State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, 100084, People's Republic of China.

The successful synthesis of the single to few layer transition metal dichalcogenides has opened a new era in the nanoelectronics. For their efficient implementations in the electronic devices while taking care of their overheating issues, the characterization of their thermal transport properties is extremely vital. So, we have systematically investigated the thermal transport properties of monolayer transition metal dichalcogenides MX (M = Mo, W; X = S, Se, Te) by combining the first-principles calculations with Boltzmann transport equation. We find that monolayer WTe possesses the lowest lattice thermal conductivity κ (33:66 WmK at 300 K) among these six semiconducting materials, in contrast to the highest κ (113:97 WmK at 300 K) of WS among them. Further analyses reveal that the higher (lower) anharmonic and isotopic scatterings together with the lower (higher) phonon group velocities lead to the lowest (highest) value of κ in WTe (WS) monolayer. In addition, we have also calculated the cumulative thermal conductivity κ as a function of mean free path, which indicates that the nanostructures with the length of about 400 nm would reduce κ drastically. These results offer important understanding from thermal conductivity point of view to design the 2D transition metal dichalcogenides MX (M = Mo, W; X = S, Se, Te) electronics.
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http://dx.doi.org/10.1038/s41598-019-40882-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418116PMC
March 2019

Health-related Quality of Life for Abiraterone Plus Prednisone Versus Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer: Results from a Phase II Randomized Trial.

Eur Urol 2019 06 24;75(6):940-947. Epub 2018 Dec 24.

Department of Medical Oncology, BC Cancer Vancouver Centre, Vancouver, BC, Canada; Department of Urological Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background: Abiraterone and enzalutamide are associated with side effects that may impair health-related quality of life (HRQoL).

Objective: To assess patient-reported HRQoL, depression symptoms, and cognitive function for abiraterone versus enzalutamide.

Design, Setting, And Participants: We randomized 202 patients in a phase II study of abiraterone versus enzalutamide for first-line treatment of metastatic castration-resistant prostate cancer (ClinicalTrials.gov: NCT02125357).

Intervention: Patients completed Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Patient Health Questionnaire-9 (PHQ-9) questionnaires, and Montreal Cognitive Assessment (MoCA) cognitive assessments at baseline and on treatment.

Outcome Measurements And Statistical Analysis: To compare the change in FACT-P scores over time between treatment arms, we used a mixed model for repeated measures (MMRM). For FACT-P domains where there was an interaction between the treatment arm and age, we constructed separate models for patients aged <75 and ≥75yr. We compared the proportion of patients with clinically meaningful change from baseline for FACT-P, and the proportion of patients with an abnormal score and median change from baseline for PHQ-9 and MoCA using Fisher's exact test and Mann-Whitney U test.

Results And Limitations: In the MMRM analysis, there was a positive test for interaction in the treatment arm by age for total FACT-P (p=0.048). FACT-P change from baseline over time was better for abiraterone than for enzalutamide in the ≥75-yr model (p=0.003), with no difference in the <75-yr model (p>0.9). A higher proportion of patients experienced clinically meaningful worsening with enzalutamide for the physical and functional well-being domains (37% vs 21%, p=0.013; 39% vs 23%, p=0.015). The distribution of change in PHQ-9 scores from baseline favored abiraterone at weeks 4, 8, and 12. These analyses were not prespecified, and results should be considered to be hypothesis generating.

Conclusions: Patient-reported outcomes favored abiraterone compared with enzalutamide with differences in FACT-P HRQoL and PHQ-9 depression scores. Differences in the total FACT-P scores were seen only in the elderly patient subgroup.

Patient Summary: In this report, we examined the change in patient-reported quality-of-life scores from the start of treatment over time for patients treated with abiraterone versus enzalutamide for metastatic castration-resistant prostate cancer. We found that elderly patients treated with abiraterone had better quality of life over time, with no difference between treatments for the younger subgroup of patients.
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http://dx.doi.org/10.1016/j.eururo.2018.12.015DOI Listing
June 2019

Clinical effectiveness of docetaxel for castration-sensitive prostate cancer in a real-world population-based analysis.

Prostate 2019 02 28;79(3):281-287. Epub 2018 Oct 28.

Division of Medical Oncology, University of British Columbia, BC Cancer, Vancouver, British Columbia.

Background: Adding docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has known efficacy, with an overall survival benefit in Phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains undefined.

Patients And Methods: We conducted a population-based retrospective review using the British Columbia Provincial Pharmacy Database. To be included, patients had to have castration-sensitive prostate cancer not previously treated (except in the adjuvant setting) and have received at least one cycle of docetaxel, with complete records available for review. Safety and clinical effectiveness were evaluated.

Results: From April 2015 to February 2017, we identified 183 cases; 156 met inclusion criteria. Most patients had high-volume disease (80%). All 6 planned docetaxel cycles were delivered in 126 cases (81%). Dose reductions and delays were required in 39% and 16% of cases. Grade 3-4 adverse events were noted in 40%, with no treatment-related deaths. The rate of febrile neutropenia was 18% and was significantly associated with the presence of high-volume disease (P = 0.038). PSA ≤ 0.2 ng/L was achieved in 27% of patients after 6 months of ADT and maintained in 16% after 12 months. Patients with over 20 bone metastases had worse time to castration resistant prostate cancer (CRPC) and time to treatment for CRPC, and a trend toward worse overall survival. CRPC developed in 41% within 1 year, with a median time to CRPC of 14.4 months. Treatment for CRPC was given in 84 cases, with 90% receiving either abiraterone or enzalutamide in the first-line, with a PSA decline ≥50% occurring in 47%.

Conclusions: The effectiveness of docetaxel with ADT in a general population of patients with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the published studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to reported outcomes.
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http://dx.doi.org/10.1002/pros.23733DOI Listing
February 2019

Synthesis of self-assembled PtPdAg nanostructures with a high catalytic activity for oxygen reduction reactions.

Nanoscale 2018 Sep;10(36):17140-17147

Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, China.

Designing a self-assembling structure for a Pt-based catalyst offers a great opportunity to enhance the electrocatalytic performance and maximize the use of precious metals. Herein, we report an etching method based on thermal treatment for the removal of less active metals from Pt-based alloys for the enhancement of the oxygen reduction reaction. PtPdAg nanostructures' self-assembly can be easily controlled to the dimer stage or nanowires by stirring the nanoparticles in formamide with or without potassium iodide under heat for specific times. Thus oxygen reduction reaction-favoring PtPdAg hollow nanoparticle, nanodimer and nanowire catalysts are synthesized, all of which have been demonstrated to be promoting factors for the ORR. In a Pt-based catalyst, the arrangement and configuration of the surface or topmost few layer atoms influence the adsorption of oxygen and activation for ORR. The PtPdAg dimer catalyst shows excellent ORR activity compared to other PtPdAg nanostructures and commercial Pt/C i.e. 7.2 times higher specific activity and 4.1 times higher mass activity. We further carried out DFT calculations and from the results, we conclude that the most chemically inequivalent structure such as PtPdAg/C nanodimer alloys possesses the weakest oxygen binding energy.
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http://dx.doi.org/10.1039/c8nr03593hDOI Listing
September 2018

A review on geopolymers as emerging materials for the adsorption of heavy metals and dyes.

J Environ Manage 2018 Oct 23;224:327-339. Epub 2018 Jul 23.

Department of Chemical Engineering, 32610, Bandar Seri Iskandar, Perak, Malaysia.

The world water resources are contaminated due to discharge of a large number of pollutants from industrial and domestic sources. A variety of a single and multiple units of physical, chemical, and biological processes are employed for pollutants removal from wastewater. Adsorption is the most widely utilized process due to high efficiency, simple procedure and cost effectiveness. This paper reviews the research work carried out on the use of geopolymer materials for the adsorption of heavy metals and dyes. Geopolymers possess good surface properties, heterogeneous microstructure and amorphous structure. The performance of geopolymers in the removal of heavy metals and dyes is reported comparable to other materials. The pseudo-second order kinetics and Langmuir isotherm models mostly fit to the adsorption data suggesting homogeneous distribution of adsorption sites with the formation of monolayer adsorbate on the surface of geopolymers. Adsorption of heavy metals and dyes onto geopolymers is spontaneous, endothermic and entropy driven process. Future research should focus on the enhancement of geopolymer performance, testing on pollutants other than heavy metals and dyes, and verification on real wastewater in continuous operation.
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http://dx.doi.org/10.1016/j.jenvman.2018.07.046DOI Listing
October 2018

Molecular Diagnostics in Esophageal and Gastric Neoplasms: 2018 Update.

Clin Lab Med 2018 06;38(2):357-365

Department of Pathology and Anatomical Sciences, Jacobs School of Buffalo, 955 Main Street, Buffalo, NY 14203, USA.

Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease.
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http://dx.doi.org/10.1016/j.cll.2018.02.009DOI Listing
June 2018

Molecular Diagnostics in the Neoplasms of Small Intestine and Appendix: 2018 Update.

Clin Lab Med 2018 06;38(2):343-355

Department of Pathology, Harper University Hospital, Detroit Medical Center, 3990 John R Street, Detroit, MI 48201, USA.

Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix.
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http://dx.doi.org/10.1016/j.cll.2018.03.002DOI Listing
June 2018

Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018.

Clin Lab Med 2018 06;38(2):311-342

Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA; Pathology Laboratories, Michigan Surgical Hospital, 21230 Dequindre Road, Warren, MI 48091, USA.

The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management.
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http://dx.doi.org/10.1016/j.cll.2018.02.008DOI Listing
June 2018

A randomized phase II study of pelareorep and docetaxel or docetaxel alone in men with metastatic castration resistant prostate cancer: CCTG study IND 209.

Oncotarget 2018 Jan 17;9(8):8155-8164. Epub 2018 Jan 17.

Canadian Cancer Trials Group, Kingston, ON, Canada.

Background: Pelareorep is an oncolytic virus with activity in many cancers including prostate. It has synergism with microtubule-targeted agents. We undertook a clinical trial evaluating pelareorep in mCRPC patients receiving docetaxel.

Patients And Methods: In this randomized, open-label phase II study, patients received docetaxel 75mg/m on day 1 of a 21-day cycle and prednisone 5mg twice daily, in combination with pelareorep (arm A) or alone (arm B). The primary endpoint was 12 weeks lack of disease progression rate (LPD).

Results: Eighty-five pts were randomized. Median age was 69, ECOG performance status was 0/1/2 in 31%/66%/3% of patients. Bone/regional lymph node/liver metastases were present in 98%/24%/6%. The median prognostic score was slightly higher in Arm A (144 vs. 129 p= 0.005). Adverse events were as expected but more prevalent in arm A. The 12-week LPD rate was 61% and 52.4% in arms A/B (p=0.51). Median survival was 19.1 on Arm A and 21.1 months on Arm B (HR 1.83; 95% CI 0.96 to 3.52; p=0.06). No survival benefit of pelareorep was found.

Conclusion: Pelareorep with docetaxel was tolerable with comparable LPD in both arms but response and survival were inferior and so this combination does not merit further study.
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http://dx.doi.org/10.18632/oncotarget.24263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814290PMC
January 2018

Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer.

Cancer Discov 2018 04 24;8(4):444-457. Epub 2018 Jan 24.

Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

Primary resistance to androgen receptor (AR)-directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 patients with treatment-naïve mCRPC to abiraterone or enzalutamide and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in and were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance. Somatic alterations in , previously linked to reduced tumor dependency on AR signaling, were also independently associated with rapid resistance. Although detection of amplifications did not outperform standard prognostic biomarkers, gene structural rearrangements truncating the ligand binding domain were identified in several patients with primary resistance. These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers. Leveraging plasma specimens collected in a large randomized phase II trial, we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer. Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice. .
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http://dx.doi.org/10.1158/2159-8290.CD-17-0937DOI Listing
April 2018

Trimetallic PtCoFe Alloy Monolayer Superlattices as Bifunctional Oxygen-Reduction and Ethanol-Oxidation Electrocatalysts.

Small 2017 06 8;13(24). Epub 2017 May 8.

Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China.

A synthesis strategy for the preparation of trimetallic PtCoFe alloy nanoparticle superlattices is reported. Trimetallic PtCoFe alloy monolayer array of nanoparticle superlattices with a large density of high index facets and platinum-rich surface are successfully prepared by coreduction of metal precursors in formamide solvent. The concentration of cetyl trimethyl ammonium bromide plays a vital role for the formation of a monolayer array of nanoparticle superlattices, while the size of nanoparticles is determined by NaI. The prepared monolayer array of nanoparticle superlattices is the superior catalyst for oxygen reduction reaction as well as for ethanol oxidation owing to their specific structural and compositional characteristics.
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http://dx.doi.org/10.1002/smll.201700250DOI Listing
June 2017

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.

J Clin Oncol 2016 11 30;34(32):3914-3920. Epub 2016 Sep 30.

Sharlene Gill and Malcolm Moore, BC Cancer Agency, Vancouver; Muhammad Zulfiqar, BC Cancer Agency, Abbotsford; Thuan Do, BC Cancer Agency, Surrey; Wendy Yin Han Lam, Burnaby Hospital Cancer Centre, Burnaby, British Columbia; Yoo-Joung Ko, Sunnybrook Health Sciences Centre; Malcolm Moore, Princess Margaret Hospital, Toronto; Christine Cripps, Ottawa Hospital Cancer Centre, Ottawa; Sukhbinder Dhesy-Thind, Juravinski Cancer Centre, Hamilton; Pawel Zalewski, RSM Durham Regional Cancer Centre, Oshawa; Pablo Cano, Sudbury Regional Hospital, Sudbury, Ontario; Annie Beaudoin, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Helene Grassin and John Stewart, Sanofi Canada, Laval, Quebec; and Scot Dowden, Alberta Health Service, Calgary, Alberta, Canada.

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.
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http://dx.doi.org/10.1200/JCO.2016.68.5776DOI Listing
November 2016

Current applications of molecular genetic technologies to the diagnosis and treatment of cutaneous melanocytic neoplasms.

Clin Lab Med 2013 Dec 15;33(4):881-90. Epub 2013 Oct 15.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Indianapolis, IN 46202-3082, USA.

Decades of research have brought knowledge to a point where physicians are beginning to understand human disease processes like oncogenesis on a molecular level. Molecular technologies are now being applied to current clinical settings such as the diagnosis and treatment of cutaneous melanocytic neoplasms. In particular, dermatopathologists are using fluorescence in situ hybridization to aid in the diagnosis of challenging melanocytic neoplasms. Pathologists are working with oncologists to use the sequences of specific genes in melanomas to choose more effective treatments. This article discusses how these technologies are altering the ways in which cutaneous melanocytic neoplasms are diagnosed and treated.
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http://dx.doi.org/10.1016/j.cll.2013.08.008DOI Listing
December 2013

Molecular diagnostics in the neoplasms of the pancreas, liver, gall bladder, and extrahepatic biliary tract.

Clin Lab Med 2013 Dec 9;33(4):875-80. Epub 2013 Oct 9.

Department of Pathology, Detroit Medical Center, Karmanos Cancer Center, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA.

Pancreatic neoplasms, including ductal adenocarcinoma, intraductal papillary mucinous neoplasm, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and ampullary carcinoma, are associated with different genetic abnormalities. Liver neoplasms, including hepatic adenomas, hepatocellular carcinomas, and cholangiocarcinomas, are associated with identifiable risk factors and genetic changes. Gall bladder adenomas and adenocarcinomas arise from distinct molecular pathways. The molecular abnormalities seen in these tumors are not used routinely in the molecular diagnostic laboratory.
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http://dx.doi.org/10.1016/j.cll.2013.08.002DOI Listing
December 2013

Molecular diagnostics in esophageal and gastric neoplasms.

Clin Lab Med 2013 Dec 15;33(4):867-73. Epub 2013 Oct 15.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Indianapolis, IN 46202-3082, USA. Electronic address:

Esophageal carcinoma is the most rapidly increasing tumor in incidence in the United States. It has an established association with a precursor lesion (Barrett esophagus). Gastric carcinoma (GC) is the second leading cause of cancer death in the world. The prognosis for patients with advanced stage GC and esophageal carcinoma is poor. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset of GC. HER-2 overexpressing tumors are eligible for HER-2 targeted therapies, which lead to a better survival in these patients.
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http://dx.doi.org/10.1016/j.cll.2013.08.006DOI Listing
December 2013

Molecular diagnostics in the neoplasms of small intestine and appendix.

Clin Lab Med 2013 Dec 15;33(4):861-6. Epub 2013 Oct 15.

Department of Pathology, PGY-3 Detroit Medical Center, Harper University Hospital, Wayne State University School of Medicine, 3990 John R Street, Detroit, MI 48201, USA.

Adenocarcinoma of the small intestine is relatively rare in comparison to colorectal carcinoma. Adenocarcinoma of the small intestine arises through the adenoma-carcinoma sequence in the colon. However, adenocarcinomas arising in the background of inflammatory bowel disease develop through the dysplasia-carcinoma sequence. Most of the cases occur in the duodenum; however, adenocarcinoma occurring in association with Crohn disease is more common in the ileum.
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http://dx.doi.org/10.1016/j.cll.2013.08.007DOI Listing
December 2013

Molecular diagnostics in colorectal carcinoma.

Clin Lab Med 2013 Dec;33(4):835-59

Pathology Department, Harper University Hospital, Detroit Medical Center, Wayne State University School of Medicine, 3990 John R Street, Detroit, MI 48201, USA.

Molecular pathogenesis and classification of colorectal carcinoma are based on the adenoma-carcinoma sequence in the Vogelstein model, serrated polyp pathway, and microsatellite instability. The genetic basis for hereditary nonpolyposis colorectal cancer is based on detection of genetic mutations. Genetic testing for Lynch syndrome includes microsatellite instability, methylator phenotyping, BRAF mutation, and molecular testing. Molecular makers include quantitative multigene reverse transcriptase-polymerase chain reaction assay and KRAS and BRAF mutation analysis. Potential biomarkers include one-step nucleic acid amplification and epigenetic inactivation of endothelin 2 and endothelin 3 in colon cancer. Molecular screening approaches in colorectal cancer using stool DNA are under investigation.
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http://dx.doi.org/10.1016/j.cll.2013.10.001DOI Listing
December 2013

Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens confirmed by immunocytochemical stains on liquid base specimens: Two study cases with review of the literature.

Cytojournal 2013 20;10. Epub 2013 May 20.

Department of Pathology, Wayne State University, Detroit Medical Center, Karmanos Cancer Institute, MI, USA.

Only a few cases of adenocarcinoma (ACA) metastatic to the female lower genital tract diagnosed on cervicovaginal Pap smear have been reported during the past several decades. Both conventional and liquid based cytology (LBC) have limited sensitivity and specificity in diagnosing metastatic disease and immunocytochemical (ICC) staining may be needed for confirming the diagnosis. We present two cases of metastatic colorectal ACA diagnosed on cervicovaginal ThinPrep (TP) Pap smears, with one confirmed by ICC staining method. Recognition of extra-uterine malignancy in the cervicovaginal cytology specimen is critical for the disease diagnosis, prognosis, and the treatment. ICC staining performed on the residual LBC specimen is an important methodology to confirm the diagnosis.
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http://dx.doi.org/10.4103/1742-6413.112297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709382PMC
July 2013

Enhanced autoimmunity associated with induction of tumor immunity in thyroiditis-susceptible mice.

Thyroid 2013 Dec 11;23(12):1590-9. Epub 2013 Sep 11.

1 Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, Michigan.

Background: Immunotherapeutic modalities to bolster tumor immunity by targeting specific sites of the immune network often result in immune dysregulation with adverse autoimmune sequelae. To understand the relative risk for opportunistic autoimmune disorders, we studied established breast cancer models in mice resistant to experimental autoimmune thyroiditis (EAT). EAT is a murine model of Hashimoto's thyroiditis, an autoimmune syndrome with established MHC class II control of susceptibility. The highly prevalent Hashimoto's thyroiditis is a prominent autoimmune sequela in immunotherapy, and its relative ease of diagnosis and treatment could serve as an early indicator of immune dysfunction. Here, we examined EAT-susceptible mice as a combined model for induction of tumor immunity and EAT under the umbrella of disrupted regulatory T cell (Treg) function.

Methods: Tumor immunity was evaluated in female CBA/J mice after depleting Tregs by intravenous administration of CD25 monoclonal antibody and/or immunizing with irradiated mammary adenocarcinoma cell line A22E-j before challenge; the role of T cell subsets was determined by injecting CD4 and/or CD8 antibodies after tumor immunity induction. Tumor growth was monitored 3×/week by palpation. Subsequent EAT was induced by mouse thyroglobulin (mTg) injections (4 daily doses/week over 4 weeks). For some experiments, EAT was induced before establishing tumor immunity by injecting mTg+interleukin-1, 7 days apart. EAT was evaluated by mTg antibodies and thyroid infiltration.

Results: Strong resistance to tumor challenge after Treg depletion and immunization with irradiated tumor cells required participation of both CD4(+) and CD8(+) T cells. This immunity was not altered by induction of mild thyroiditis with our protocol of Treg depletion and adjuvant-free, soluble mTg injections. However, the increased incidence of mild thyroiditis can be directly related to Treg depletion needed to achieve strong tumor immunity. Moreover, when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced.

Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment.
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http://dx.doi.org/10.1089/thy.2013.0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868308PMC
December 2013

2-(4-Isobutyl-phen-yl)-1-(morpholin-4-yl)propan-1-one.

Acta Crystallogr Sect E Struct Rep Online 2012 Sep 4;68(Pt 9):o2637. Epub 2012 Aug 4.

In the title compound, C(17)H(25)NO(2), the morpholine ring adopts a chair conformation. The benzene ring makes a dihedral angle of 39.81 (13)° with the basal plane of the morpholine group.
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http://dx.doi.org/10.1107/S1600536812033442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435664PMC
September 2012

2-(6-Meth-oxy-naphthalen-2-yl)-1-(morpholin-4-yl)propan-1-one.

Acta Crystallogr Sect E Struct Rep Online 2012 Sep 4;68(Pt 9):o2636. Epub 2012 Aug 4.

In the title compound, C(18)H(21)NO(3), the naphthalene group and the basal plane of the morpholine ring (r.m.s. deviations = 0.0177 and 0.0069 Å, respectively) are oriented at a dihedral angle of 44.0 (2)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions.
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http://dx.doi.org/10.1107/S1600536812034083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435663PMC
September 2012