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51.
Bromadiolone (BRD), a substituted 4-hydroxycoumarin derivative, is known to possess anti-coagulant activity with acute toxicity. In this paper, we report a study on the interaction of bromadiolone with the plasma proteins bovine serum albumin (BSA) and human serum albumin (HSA), using the intrinsic fluorescence emission properties of bromadiolone. Bromadiolone is weakly fluorescent in aqueous buffer medium, with an emission at 397 nm. Binding of bromadiolone with serum albumins (SA) leads to a marked enhancement in the fluorescence emission intensity and steady state fluorescence anisotropy (rss), accompanied by a blueshift of 10 nm. In the serum albumin–bromadiolone complex, selective excitation of tryptophan (Trp) residue results in emission from bromadiolone, thereby indicating a Förster type energy transfer from Trp to BRD. This quenching of Trp fluorescence by BRD was used to estimate the binding constant of the SA–BRD complex. The binding constants for BRD with BSA and HSA were 7.5 × 104 and 3.7 × 105 L mol−1, respectively. Based on this, a new method involving SA as fluorescence-enhancing reagent for estimation of BRD in aqueous samples has been suggested. The detection limits of bromadiolone under the optimum conditions were 0.77 and 0.19 μg mL−1 in presence of BSA and HSA, respectively. 相似文献
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53.
Subbiah Alwarappan Guodong Liu Chen-Zhong Li 《Nanomedicine : nanotechnology, biology, and medicine》2010,6(1):52-57
In this work we have evaluated the performance of electrochemically pretreated single-walled carbon nanotubes (SWCNTs) toward the electrochemical detection of dopamine in the presence of ascorbic acid and uric acid at physiological pH. Results indicated that the electrochemically pretreated SWCNTs showed a selective and enhanced electroanalytical response with minimal electrode fouling toward the detection of dopamine than their untreated counterparts. The observed behavior is attributed to the negatively charged layer present on the SWCNTs originating from the rupture of the basal plane present on the end caps following electrochemical pretreatment. The rupture of basal plane is evident from surface Raman measurements. The negatively charged surface selectively allows the cationic dopamine toward the electrode and repels the anionic ascorbate and uric acid when they coexist in the same solution under physiological pH. A limit of detection of about 15 nM is obtained with these electrodes for the detection of dopamine in the presence of ascorbic acid and uric acid.From the Clinical EditorThe performance of electrochemically pretreated single-walled carbon nanotubes (SWCNTs) was studied toward the electrochemical detection of dopamine. These SWCNTs showed a selective and enhanced response toward the detection of dopamine. A limit of detection of about 15 nM is obtained with these electrodes for the detection of dopamine in the presence of ascorbic acid and uric acid. 相似文献
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55.
Rishi Agarwal Kimberly Koenig Eric Rohren Vivek Subbiah 《JOURNAL OF BREAST CANCER》2014,17(3):287-290
Metaplastic breast cancer (MpBC) is an extremely rare breast cancer subtype, characterized by a heterogeneous phenotype. MpBC aggressive biology is attributed to its stem cell-like characteristics. Since these tumors are largely chemoresistant, novel targeted therapies should be explored. Herein, we report the clinical course of a 59-year-old African American woman with MpBC with a PIK3CA mutation in codon 545, exon 10 (GAG to AAG; p.Glu545Lys) and a TP53 mutation in codon 286, exon 8 (GAA to AAA; p.Glu286Lys). The same mutations were observed in the primary and secondary sites. The patient was treated with a molecularly matched therapy using a combined antiangiogenic and mammalian target of rapamycin kinase inhibitor strategy that included liposomal doxorubicin, bevacizumab, and temsirolimus. Partial remission was achieved. In this report, the scientific rationale underlying the activity of this combination was explored. In conclusion, patients may benefit from being offered molecular profiling early during the course of the disease to receive a therapy guided accordingly. 相似文献
56.
Jennifer J. Wheler Barbara A. Parker Jack J. Lee Johnique T. Atkins Filip Janku Apostolia M. Tsimberidou Ralph Zinner Vivek Subbiah Siqing Fu Richard Schwab Stacy Moulder Vicente Valero Maria Schwaederle Roman Yelensky Vincent A. Miller M Philip J. Stephens Funda Meric-Bernstam Razelle Kurzrock 《Oncotarget》2014,5(9):2349-2354
Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient''s tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via ‘crosstalk’). The ‘molecular individuality’ of these tumors suggests that a customized strategy, using an “N-of-One” model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors. 相似文献
57.
Background
Signet ring cell carcinoma (SRCC) accounts for less than 1% of all colon cancers. We examined the clinicopathological features and prognosis of signet ring cell and mucinous adenocarcinoma (MCC) of colon.Methods
A total of 206 patients diagnosed with SRCC from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected.Results
Out of 206 patients, 173 (84%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous cell (MCC) and non-mucinous adenocarcinoma (NMCC) of colon. Pathological T-stages were as follows: T1 =3%, T2 =5%, T3 =34%, T4 =26%, and unknown 32%. Of the total, 22.3% were located in cecum, 7.7% in appendix, 21.8% in ascending colon, 7.7% in hepatic flexure of colon, 11% in transverse colon, 2.9% in splenic flexure 4.4% in descending colon, and 15.5% in sigmoid colon. 46.5% were lymph node positive, 21% were lymph node negative, and 32.5% were unknown. SRCC were in general poorly differentiated tumors (57%), small proportion of patients included were well-differentiated tumors with focal signet ring cell pathology (10%) and in 33% grade was unknown. Among stage 3 patients, 34% patients received only surgery while 64% received surgery with adjuvant chemotherapy and 2% received chemotherapy alone. The stage specific 5-year survivals for SRCC, MCC and NMCC were--Stage I: 100%, 61%, and 41% respectively (P<0.0001); Stage II: 42%, 58% and 32% respectively (P<0.0001); Stage III: 19%, 41% and 47% respectively (P=0.0002); Stage IV: 1.5%, 7% and 31% respectively (P<0.0001). Median survival of SRCC compared to NMCC was 18.6 vs. 46 months (P<0.0001) and mucinous cell adenocarcinoma versus NMCC was 47.8 and 46 months (P=0.63) respectively.Conclusions
SRCC of colon has poor survival rates compared to other histological subtypes. SRCC presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and NMCC of colon. Due to rarity of this disease further prospective multi-institute studies are required for in-depth understanding of this disease. 相似文献58.
Vivek Subbiah 《Current oncology reports》2014,16(9):1-10
Non-small-cell lung cancer usually carries a dismal prognosis. Novel treatment approaches are clearly warranted. Immunotherapy has emerged as a promising area of research developing agents that manipulate the immune system to induce antitumor responses while avoiding major toxicity. New vaccines and checkpoint inhibitors are currently undergoing investigation in phase II and phase III clinical trials. In advanced non-small-cell lung cancer (NSCLC), belagenpumatucel-L, an allogeneic cell vaccine directed against transforming growth factor β in the tumor microenvironment, knocks down the immune suppression caused by the tumor and has demonstrated a dose- and time-dependent efficacy in some subgroups of patients. L-BLP25 and TG4010 are both antigenic vaccines that target mucin 1, whose encoding proto-oncogene is commonly mutated in solid tumors. The L-BLP25 vaccine achieved a significant improvement in overall survival in the subgroup of patients with stage IIIB NSCLC treated with chemoradiotherapy. TG4010 vaccination resulted in better progression-free survival when added to cisplatin–gemcitabine chemotherapy. These results are being addressed in the currently ongoing phase III TIME trial. In the adjuvant setting, MAGE-A3, an antigen-based vaccine, showed promising results in melanoma-associated antigen A3 positive lung cancer patients who underwent resection in the phase II study; however, no improvement in progression-free survival was observed in the phase III MAGRIT study. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. It has improved overall survival in patients with advanced NSCLC who achieve seroconversion. Ipilimumab, an immune checkpoint inhibitor that targets cytotoxic T-lymphocyte antigen 4, demonstrated improved progression-free survival in advanced NSCLC patients who received the drug after chemotherapy in a phased regimen. Finally, anti-programmed death receptor 1 agents have achieved durable response rates in phase I studies. This review gives an overview of the current data and the most promissory immunotherapeutic agents for NSCLC. 相似文献
59.
Calves were infected intranasally and intratracheally with Newcastle disease virus (NDV), an avian paramyxovirus. Clinical signs, viral replication, and antibody production were evaluated. This study showed that NDV replicated in calves, as evidenced by development of NDV-specific humoral and mucosal antibody responses, but was attenuated in this unnatural host. These results suggest that NDV has the potential for development as a host-range-restricted, intranasal vaccine vector for cattle that lack preexisting immunity to NDV. 相似文献
60.
Kishimoto TK Viswanathan K Ganguly T Elankumaran S Smith S Pelzer K Lansing JC Sriranganathan N Zhao G Galcheva-Gargova Z Al-Hakim A Bailey GS Fraser B Roy S Rogers-Cotrone T Buhse L Whary M Fox J Nasr M Dal Pan GJ Shriver Z Langer RS Venkataraman G Austen KF Woodcock J Sasisekharan R 《The New England journal of medicine》2008,358(23):2457-2467