Phase II study of paclitaxel and cisplatin for advanced urothelial cancer

PURPOSE: We examined the role of paclitaxel and cisplatin as first line therapy for metastatic urothelial cancer. MATERIALS AND METHODS: A total of 34 patients were enrolled in this study, and all were eligible for treatment and assessable for response. Patients received 135 mg./m.2 paclitaxel intravenously for 3 hours followed by 70 mg./m.2 cisplatin for 2 hours every 3 weeks to a maximum of 6 cycles. RESULTS: Of the patients 70% experienced a major response to treatment, which was partial/regression in 38% and complete in 32%. Toxicity was manageable with no episodes of grade 4 leukopenia or thrombocytopenia. Nonhematological toxicities included primarily nausea, anorexia and neuropathy, which rarely were severe. CONCLUSIONS: This regimen of paclitaxel and cisplatin is effective, safe and convenient to administer in an outpatient setting for advanced urothelial cancer.     

Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC₅₀ values of 10.71 μM and 11.83 μM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

Schematic representation of (HTPu–var-1-G4) located at the 3′ end, formation of G-quadruplex, model of the G-quadruplex structure, base stacking between G-quadruplex planes, G-quadruplex structure-peptide complex and twisting of G-quadruplex planes upon peptide binding.     

Evaluation of hearing loss in tympanic membrane perforation

To evaluate and analyse the hearing loss in tympanic membrane perforation based on size, site and duration of perforation. The material for this study was comprised of 100 patients of either sex and of age 15?years and above selected randomly. Size of tympanic membrane perforation was assessed under microscope using calibrated wire look. Patients were divided into three groups according to size; group I (0-9?mm(2)), Group II (9-30?mm(2)), Group III (≥?30?mm(2)); according to site into anterior and posterior group; according to involvement of malleus into malleolar and non malleolar and according to duration into Group A (<1?year), Group B (1-5?years), Group C (≥?5?years). Hearing loss was measured in each case with pure tone audiometry. Data was analysed statistically using paired t-test. Hearing loss increased as the perforation size increased [I vs. II (t?-?4.23, p??0.05). Hearing loss was more in malleolar perforation (t?-?5.74, p?相似文献   

Intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy for choroidal neovascularization in age-related macular degeneration

PURPOSE: To report the outcome for eyes treated with intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN AND PARTICIPANTS: Interventional, consecutive, retrospective case series including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg intravitreal injection of bevacizumab followed by PDT within a 2-week period were reviewed. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and need for retreatment. RESULTS: Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9 (40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes (48%) required only a single combined treatment for CNV resolution at the 12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up required only a single combined treatment. There were no complications such as endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings suggest that eyes treated with both intravitreal injection of bevacizumab and PDT require none to a minimal number of re-treatments to have stabilization of vision, even at 12 months of follow-up. Further investigation with large controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.     

Therapeutic potential of oxazole scaffold: a patent review (2006–2017)

ABSTRACT

Introduction: Oxazoles are oxygen and nitrogen containing five membered heterocyclic ring systems that are present in various anticancer, antimicrobial, antihyperglycemic, anti-inflammatory agents etc. of natural origin. These pharmacologically active oxazole derivatives have attracted numerous researchers to explore this scaffold for the design and development of newer potential therapeutic agents. A large number of synthetic oxazole containing molecules have been reported over the period that exhibited wide spectrum of pharmacological profiles. Some of them have shown promising therapeutic potential and have qualified for both preclinical and clinical evaluations.

Areas covered: In this review, the patents (published during 2006–2017) focusing on the biological potential of oxazoles have been covered. Therapeutic applications and various techniques/assays employed for the in vitro/in vivo evaluation of patented derivatives have been discussed majorly.

Expert opinion: Chemically oxazole offers three positions for substitution. These substituted oxazole derivatives of natural as well as synthetic origin have numerous pharmacological applications including anticancer, anti-Alzheimer’s, anti-hyperglycemic, anti-inflammatory, antibacterial etc. Their pharmacological actions are mainly mediated through enzyme/receptor involved in the particular disease. The flexible nature of this ligand for various molecular level targets (enzyme/receptor) make this heterocylce an attractive scaffold for development of effective and clinically relevant oxazole containing therapeutic agents.     

Miscarriage risk for asymptomatic women after a normal first-trimester prenatal visit

OBJECTIVE: To estimate the risk of miscarriage among asymptomatic women after a prenatal visit between 6 and 11 weeks of gestation where proof of fetal viability of a singleton was obtained by office ultrasonography at the same visit. METHODS: This was a prospective cohort study performed over 2 years (March 2004-2006) at an antenatal clinic at a large tertiary hospital in Victoria, Australia. Those recruited were 697 asymptomatic women who attended their first antenatal visit between 6 (+2 days) and 11(+6 days) weeks of gestation, where evidence of fetal cardiac activity of a singleton was obtained by office ultrasonography. The main outcome measure was rates of miscarriage, stratified by gestation at presentation. RESULTS: One case was lost to follow-up. The risk of miscarriage among the entire cohort was 11 of 696 (1.6%). The risk fell rapidly with advancing gestation; 9.4% at 6 (completed) weeks of gestation, 4.2% at 7 weeks, 1.5% at 8 weeks, 0.5% at 9 weeks and 0.7% at 10 weeks (chi(2); test for trend P=.001). Most who miscarried received their ultrasound diagnoses many weeks after their visit; five (45%) were diagnosed in the second trimester, and all but one received their ultrasound diagnoses after 10 weeks of gestation. CONCLUSION: For women without symptoms, the risk of miscarriage after attending a first antenatal visit between 6 and 11 weeks is low (1.6% or less), especially if they present at 8 weeks of gestation and beyond. Our data could be used to reassure such women that the probability of progressing to later than 20 weeks of gestation is very good.     

American Indian/Alaska Native Cancer Policy: Systemic Approaches to Reducing Cancer Disparities

Members of American Indian and Alaska Native (AI/AN) tribes have a unique political status in the United States in terms of citizenship, and that political status determines eligibility for certain unique healthcare services. The AI/AN population has a legal right to healthcare services based on treaties, court decisions, acts of Congress, Executive Orders, and other legal bases. Although the AI/AN population has a right to healthcare services, the Indian Health Service (the federal agency responsible for providing healthcare to AI/ANs) is severely underfunded, limiting access to services (including cancer care). In order to overcome distinct cancer health disparities, policy changes will be needed. This paper reviews the historical pattern of AI/AN healthcare and the challenges of the complex care needed from prevention through end-of-life care for cancer.     

Systematic Investigation of Parameters Affecting the Performance of an Agitated Filter-Dryer

A systematic experimental investigation of contact drying operation was carried out in an agitated Charles Thompson filter-dryer. In this study, the effect of process parameters (wall temperature, impeller speed, fill level) on the drying performance in the filter-dryer is quantified as a function of bed temperature and solvent concentration. In addition, the impact of drying conditions on the particle size distribution was also examined. It was found that in the range of parameters investigated, drying rate increased with wall temperature and reduced bed depth. The effect of impeller speed was variable where favorable drying conditions were strongly dependent on the particle properties. Moreover, decrease in the particle size was evident with an increase in impeller speed and decrease in the bed depth due to increased collision frequency and reduction in the fill volume both leading to particle attrition respectively. Besides, the average wall to solid heat transfer coefficient is also estimated for variable operating conditions. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2198–2213, 2013     

Reversal of Hyperoxaluria-Induced Alteration in Rat Liver by Administration of N-Acetylcysteine

The current work was designed to study the potential of N-acetylcysteine (NAC) in modulating hyperoxaluric manifestations induced by acute oxalate dose in rat liver. Hyperoxaluric conditions were induced by giving a single dose of sodium oxalate (70 mg/kg body weight) in one group, and in the other group, hyperoxaluric rats were administered NAC (200 mg/kg body weight) after 30 min of the oxalate dose. After 12 h of the above treatment, blood was taken from the orbital sinus for testing serum oxalate, and animals were sacrificed. To exploit the potential of NAC, various oxidative stress parameters [lipid peroxidation (LP) and activity of antioxidant enzymes], lipid content, and histologic analysis of rat liver were performed. The increased level of LP and activities of superoxide dismutase and catalase in hyperoxaluric rats were restored after NAC treatment. Not only the decreased amount of total lipids and phospholipids but also the increased ratio of cholesterol/phospholipid (showing decreased membrane fluidity) in hyperoxaluric rats were balanced by NAC treatment. Further restored histologic changes of liver tissue confirmed the protective antioxidant effects of the given drug. Thus, N-acetylcysteine being an extraneous antioxidant showed curative properties toward hyperoxaluric manifestations in liver.