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1.
Raman spectra of thiolated arsenicals with biological importance.
Yang, M, Sun, Y, Zhang, X, McCord, B, McGoron, AJ, Mebel, A, Cai, Y
Talanta. 2018;:520-530
Abstract
Surface enhanced Raman scattering (SERS) has great potential as an alternative tool for arsenic speciation in biological matrices. SERS measurements have advantages over other techniques due to its ability to maintain the integrity of arsenic species and its minimal requirements for sample preparation. Up to now, very few Raman spectra of arsenic compounds have been reported. This is particularly true for thiolated arsenicals, which have recently been found to be widely present in humans. The lack of data for Raman spectra in arsenic speciation hampers the development of new tools using SERS. Herein, we report the results of a study combining the analysis of experimental Raman spectra with that obtained from density functional calculations for some important arsenic metabolites. The results were obtained with a hybrid functional B3LYP approach using different basis sets to calculate Raman spectra of the selected arsenicals. By comparing experimental and calculated spectra of dimethylarsinic acid (DMAV), the basis set 6-311++G** was found to provide computational efficiency and precision in vibrational frequency prediction. The Raman frequencies for the rest of organoarsenicals were studied using this basis set, including monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMAIII), dimethylmonothioarinic acid (DMMTAV), dimethyldithioarsinic acid (DMDTAV), S-(Dimethylarsenic) cysteine (DMAIII(Cys)) and dimethylarsinous glutathione (DMAIIIGS). The results were compared with fingerprint Raman frequencies from As─O, As─C, and As─S obtained under different chemical environments. These fingerprint vibrational frequencies should prove useful in future measurements of different species of arsenic using SERS.
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Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).
Schwarz, L, Vernerey, D, Bachet, JB, Tuech, JJ, Portales, F, Michel, P, Cunha, AS
BMC cancer. 2018;(1):762
Abstract
BACKGROUND At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC. METHODS PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence. DISCUSSION The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC. TRIAL REGISTRATION ClinicalTrials.gov , NCT02959879 . Trial registration date: November 9, 2016.
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3.
Photo-modulation of zinc phthalocyanine-treated breast cancer cell line ZR-75-1 inhibited the normal tumor activity in vitro.
Zamani, ARN, Mashayekhi, MR, Jadid, MFS, Faridvand, Y, Tajalli, H, Rahbarghazi, R
Lasers in medical science. 2018;(9):1969-1978
Abstract
Regarding post-complication of convenient therapies against breast cancer, the emergence of effective approaches is essential. Photodynamic therapy is touted as a novel invasive therapeutic approach by the application of a photosensitizer promoted by laser irradiation. This study aimed to investigate the combined regime of low-level laser irradiation with zinc phthalocyanine in human breast cancer ZR-75-1 cell line. Cells were treated with 0.01 and 5 μg/ml of ZnPc for 24 h and exposed to radiation (70 mW) for 60 s. Cell viability was evaluated by MTT and flow cytometry. Cell migration capacity was monitored by scratch test, Transwell migration insert, and gelatin zymography. The function of MDR in treated cells was examined by Rhodamine 123 exclusion test. The level of GALNT11 was measured by ELISA. The expression of Bax and Bcl-2 genes was evaluated by real-time PCR. Laser irradiation and zinc phthalocyanine induced cell cytotoxicity in a dose-dependent manner. Flow cytometry analysis showed the induction of apoptotic and necrotic changes in treated cells. We found a reduction in migration rate and MMP-9 activity in cells undergoing the experimental procedure (p < 0.05). Immunofluorescence imaging revealed the intracellular accumulation of Rhodamine 123 coincided with a reduction in the level of GALNT11 in treated cells, showing the reduction of MDR activity and tumor cell resistance. Similar to flow cytometry assay, the reduction of Bcl-2 (approximately twofold) and upregulation of Bax genes were found in treated cells. Photodynamic therapy could be as an effective and alternative method for the treatment of breast cancer in a human.
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4.
Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer.
Usón Junior, PLS, Rother, ET, Maluf, FC, Bugano, DDG
Clinical colorectal cancer. 2018;(3):187-197
Abstract
BACKGROUND We performed a meta-analysis of previous reports evaluating the effect of mFIO (modified FOLFIRINOX; leucovorin, 5-fluorouracil, irinotecan, oxaliplatin) regimens in advanced pancreatic cancer. MATERIALS AND METHODS We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes. RESULTS Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association. CONCLUSION The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.
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5.
Organic Chemistry Research on the Mechanistic Elucidation of Iron Acquisition in Barley.
Namba, K, Murata, Y
Biological & pharmaceutical bulletin. 2018;(10):1502-1507
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Abstract
An organic chemistry approach to the mechanistic elucidation of iron acquisition in graminaceous plants is introduced here. To elucidate this detailed mechanism using phytosiderophores, the efficient synthesis of 2'-deoxymugineic acid (DMA), a phytosiderophore of rice, was established. The synthetic DMA was confirmed to have similar iron transport activity to that of natural mugineic acid (MA). It was also revealed that the addition of synthetic DMA, along with iron, to a rice hydroponic solution enabled the rice to grow well even under an alkaline condition, and DMA clearly showed its high potential as a fertilizer to improve food production. On the other hand, the 2'-hydroxy group of MA was confirmed to serve as a point of introduction for labeling, allowing the synthesis of various mugineic acid derivatives as molecular probes. The incorporation of fluorescent mugineic acid into cells allowed them to be clearly observed by fluorescence confocal analysis, and this provided the first direct experimental evidence of transporter-mediated internalization of mugineic acid into cells.
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Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407).
Mizusawa, J, Fukutomi, A, Katayama, H, Ishii, H, Ioka, T, Okusaka, T, Ueno, H, Ueno, M, Ikeda, M, Mizuno, N, et al
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2018;(7):841-845
Abstract
Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.
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Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity.
Schwartz, JR, Henry, JP, Kerr, KM, Flagler, MJ, Page, SH, Redman-Furey, N
Journal of cosmetic dermatology. 2018;(1):105-111
Abstract
OBJECTIVES To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function. METHODS A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption). CONCLUSIONS Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.
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A long-range emissive mega-Stokes inorganic-organic hybrid material with peripheral carboxyl functionality for As(v) recognition and its application in bioimaging.
Venkateswarulu, M, Gambhir, D, Kaur, H, Daniel, PV, Mondal, P, Koner, RR
Dalton transactions (Cambridge, England : 2003). 2017;(38):13118-13125
Abstract
We demonstrate a strategy for the recognition of As5+ in aqueous solution using a red-emissive probe based on a perylene-Cu2+ ensemble decorated with peripheral free carboxyl functionality. Single crystal analysis helped us to understand the chemical structure of the probe. To the best of our knowledge, this is the first probe for arsenic detection which emits in the red region (λem = 600 nm). The perylene-Cu2+ ensemble exhibited a mega-Stokes shift (>100 nm) with a high degree of selectivity upon interaction with As5+, which indicated that the present probe has the potential to be used as a turn-on optical sensor for selective detection of As5+ with fewer experimental limitations. The detection limit was found to be 26 nM. Inspired by its good emissive properties, the ensemble was further explored for imaging As5+ in live cells. Because of its long-range emissive nature, no autofluorescence from the cellular species was observed during the imaging process. The probe was evaluated to be non-toxic and successfully permeated the cell membrane without the help of any permeabilizing agent to image As5+.
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Intramolecular Charge Transfer and Ion Pairing in N,N-Diaryl Dihydrophenazine Photoredox Catalysts for Efficient Organocatalyzed Atom Transfer Radical Polymerization.
Lim, CH, Ryan, MD, McCarthy, BG, Theriot, JC, Sartor, SM, Damrauer, NH, Musgrave, CB, Miyake, GM
Journal of the American Chemical Society. 2017;(1):348-355
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Abstract
Photoexcited intramolecular charge transfer (CT) states in N,N-diaryl dihydrophenazine photoredox catalysts are accessed through catalyst design and investigated through combined experimental studies and density functional theory (DFT) calculations. These CT states are reminiscent of the metal to ligand charge transfer (MLCT) states of ruthenium and iridium polypyridyl complexes. For cases where the polar CT state is the lowest energy excited state, we observe its population through significant solvatochromic shifts in emission wavelength across the visible spectrum by varying solvent polarity. We propose the importance of accessing CT states for photoredox catalysis of atom transfer radical polymerization lies in their ability to minimize fluorescence while enhancing electron transfer rates between the photoexcited photoredox catalyst and the substrate. Additionally, solvent polarity influences the deactivation pathway, greatly affecting the strength of ion pairing between the oxidized photocatalyst and the bromide anion and thus the ability to realize a controlled radical polymerization. Greater understanding of these photoredox catalysts with respect to CT and ion pairing enables their application toward the polymerization of methyl methacrylate for the synthesis of polymers with precisely tunable molecular weights and dispersities typically lower than 1.10.
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Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments.
Reichardt, C, Schneider, KRA, Sainuddin, T, Wächtler, M, McFarland, SA, Dietzek, B
The journal of physical chemistry. A. 2017;(30):5635-5644
Abstract
In this study femtosecond and nanosecond time-resolved transient absorption spectroscopy was used to investigate the influence of ionic strength and complexity on the excited state dynamics of a Ru(II)-based metal-organic dyad. The bis-heteroleptic complex [Ru(bpy)2(ippy)]2+ (1), where bpy = 2,2'-bipyridine and ippy = 2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms owing to a long-lived triplet excited state derived from a metal-to-ligand charge-transfer (3MLCT) state that is equilibrium with an intraligand (3IL) state. The prolonged lifetime provides ample opportunity for bimolecular quenching of this state by oxygen; thus singlet oxygen (1O2) sensitization is very efficient. In simple aqueous solution, fast cooling within the 3MLCT manifold is followed by energy transfer to an 3IL state, which is facilitated by rotation of a pyrenyl unit about the imidazo-pyrenyl (ip) coannular bond. For solutions of 1 in high ionic strength simulated biological fluid (SBF), a more physiologically relevant solvent that contains a complex mixture of ions at pH 7.4, femtosecond studies revealed an additional excited state, possibly based on an ion-ligand interaction. This new state appearing in high ionic strength SBF was not observable in water, simple buffers, or low ionic strength SBF. These photoinduced dynamics were also affected by the presence of biomolecules such as DNA in simple buffer, whereby relaxation on the picosecond time scale was accelerated from 39 to 18 ps with DNA intercalation by 1. The increased rate of coplanarization of the pyrene and the imidazole units was attributed to DNA-induced conformational restriction of the pyrenyl unit relative to the ip bond. Quantitative changes to excited state decay rates of 1 in solutions of high ionic strength were also observed when probed on the microsecond time scale. Notably, the thermalized excited state decay pathways were altered substantially with DNA intercalation, with access to some states being completely blocked. Experimentally, this manifested in the absence of the slowest microsecond decay channel, which is normally observed for 1 in solution. The quantitative and qualitative observations from this study highlight the importance of employing biologically relevant solvents and potential biomolecule targets when the excited state dynamics and photophysical properties (under cell-free conditions) responsible for the potent photobiological effects are assessed in the context of photodynamic therapy and photodynamic inactivation.