Picomolar level electrochemical detection of hydroquinone, catechol and resorcinol simultaneously using a MoS2 nano-flower decorated graphene.

Herein, a graphene-nano-molybdenum disulphide (pGr-MoS2), synthesized from pulverized graphite and using precursors of MoS2, was investigated for the electrochemical sensing of dihydroxy benzene isomers (DHBI): hydroquinone (HQ), catechol (CA), and resorcinol (RE). Interestingly, the material could sense the three isomers simultaneously, with well-defined peaks and an adequate potential difference between each peak. The detection limits (3σ method) of HQ, CA, and RE on the glassy carbon electrode (GCE) modified with pGr-MoS2 are 10-13, 10-12, and 10-8 M (i.e., 0.1 pM, 1 pM, and 10 nM), respectively, and are the lowest reported so far for the isomers. The pGr-MoS2/GCE exhibited selectivity towards DHBI, in the presence of other toxic contaminants and metal ions such as phenol, dinitrophenol, trinitrophenol, urea and glucose, Hg(II), Ca(II), Ni(II), Zn(II), Cu(II), Na(I) and K(I). A possible mechanism for this superior selectivity of pGr-MoS2 towards DHBI is discussed based on the structural properties of pGr-MoS2 with evidence. Further, the pGr-MoS2 sensor exhibited reproducibility (with six different electrodes), stability (≥90 days), and repeatability properties. The sensing performance was successfully demonstrated in real water samples such as ground-, tap-, and river- water spiked with HQ, CA, and RE.

Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.

BACKGROUND: Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS: This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. RESULTS: Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%). CONCLUSIONS: Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising. TRIAL REGISTRATION ID: NCT01653028.

UV-B exposure enhances senescence of wheat leaves: Modulation by photosynthetically active radiation.

The alterations in structure and function of photosystem II (PS II) during the senescence of primary leaves of wheat seedlings have been compared with the changes induced by ultraviolet-B (UV-B) radiation in the presence or absence of photosynthetically active radiation (PAR). The results indicated that the senescence-induced loss in pigment content, thylakoid membrane integrity and carotenoid-to-chlorophyll (Car-to-Chl) energy transfer efficiency was intensified by exposure to UV-B radiation. Different parameters for the measurement of PS II activity, such as Chl a fluorescence, O2-evolution and thermoluminescence intensity, were altered during senescence and these alterations were furthered by UV-B irradiation. The damage of photosynthetic apparatus by UV-B exposure in the presence of PAR was less than the damage in absence of PAR. The activation of molecular defense mechanisms could be a factor in the alleviation of UV-B damage in the presence of PAR.

Ultraviolet-A induced changes in photosystem II of thylakoids: effects of senescence and high growth temperature.

Ultraviolet-A (UV-A) radiation induced changes in photosystem II (PS II) of senescing leaves of wheat seedlings were investigated. UV-A radiation did not show any significant effect on the level of photosynthetic pigments. However, the decline in F(v)/F(m) and oxygen evolution rate indicated the damaging effect of the radiation on primary photochemistry of PS II. Modification at the Q(B)-binding site was inferred from the observed downshift of peak temperature of thermoluminescence (TL) B-bands. The UV-A induced changes in PS II of chloroplasts from senescing leaves were found to be synergistically accelerated by high growth temperature.

Evaluation of topotecan and etoposide for non-Hodgkin lymphoma: correlation of topoisomerase-DNA complex formation with clinical response.

BACKGROUND: Topotecan, a topoisomerase I inhibitor, acts by stabilizing the topoisomerase DNA cleavage complex. Etoposide, a topoisomerase II inhibitor, mediates antitumor activity by stabilizing cleavage complex formed between topoisomerase II and DNA. These two agents have therapeutic activity in non-Hodgkin lymphoma. The authors report Phase I data of topotecan and etoposide combination for patients with recurrent or refractory non-Hodgkin lymphoma and correlation of topoisomerase-DNA complex formation to clinical response. METHODS: Twenty-two patients with recurrent or refractory aggressive non-Hodgkin lymphoma were treated at four dose levels of topotecan (1 mg/m(2)/day to 2.5 mg/m(2)/day). Topotecan was given at a 30-minute infusion daily with etoposide 150 mg/m(2)/day, both for 5 days. Topoisomerase-DNA covalent complex formation was measured using in vivo link assay, whereas topoisomerase I, IIalpha, and IIbeta in RNA expression levels were determined by reverse transcription-polymerase chain reaction in blood samples. The relation of these levels to clinical response was studied. RESULTS: The maximum tolerated dose of topotecan was 2.0 mg/m(2)/day for 5 days. Oropharyngeal mucositis was dose-limiting. Of 21 examinable patients, 3 patients achieved complete remission, and 5 patients achieved partial remission. Of six untreated patients who experienced a recurrence, three had complete remission, and the other three had partial remission. Drug-induced topoisomerase-DNA complex formation was observed throughout the treatment in blood samples of all the patients who responded. However, only 4 of 13 patients, who did not respond, formed covalent complex at all time points. This was statistically significant (P = 0.024). In all patients, expression levels of topoisomerase I and IIbeta mRNA remained similar to pretreatment levels, whereas topoisomerase IIalpha mRNA levels decreased dramatically by the third day. CONCLUSION: The recommended Phase II dose of topotecan with etoposide of 150 mg/m(2)/day for 5 days was 2.0 mg/m(2)/day for 5 days. Topoisomerase-DNA complex formation correlated with response to treatment.