A Pilot Phase II Study of Digoxin in Patients with Recurrent Prostate Cancer as Evident by Rising PSA

Background: Digoxin was found to inhibit prostate cancer (PCa) growth via the inhibition of HIF-1α synthesis in a mouse model. We hypothesized that a therapeutic dose of digoxin could inhibit human PCa growth and disease progression. Methods: An open label, single arm pilot study was performed. Patients (pts) with non-metastatic, biochemically relapsed PCa with prostate specific antigen doubling time (PSADT) of 3 -24 months and no hormonal therapy within the past 6 months were enrolled. All pts had testosterone 50 ng/dL at baseline. Digoxin was taken daily with dose titration to achieve a target therapeutic level (0.8 – 2 ng/ml); patients had routine follow-up including cardiac monitoring with 12-lead electrocardiograms (ECGs) and digoxin levels. The primary endpoint was the proportion of pts at 6 months post-treatment with a PSADT 200% from the baseline. HIF-1α downstream molecule vascular endothelial growth factor (VEGF) was measured in plasma.Results: Sixteen pts were enrolled and 14 pts finished the planned 6 months of treatment. Twenty percent (3/15) of the pts had PSA decrease 25% from baseline with a medium duration of 14 months. At 6 months, 5 of 13 (38%) pts had PSADT 200% of the baseline PSADT and were continued on study for an additional 24 weeks of treatment. Two patients had durable PSA response for more than 1 year. Digoxin was well tolerated with possible relation of one grade 3 back pain. No patients had evidence of digoxin toxicity. The digoxin dose was lowered in 2 patients for significant ECGs changes (sinus bradycardia and QT prolongation), and there were probable digoxin-related ECG changes in 3 patients. Plasma VEGF was detected in 4 (25%) patients. Conclusions: Digoxin was well tolerated and showed a prolongation of PSDAT in 38% of the patients. However, there was no significant difference comparing that of similar patients on placebo from historical data. Digoxin at the dose used in this study may have limited benefit for patients with biochemically relapsed prostate cancer

Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin and Paclitaxel in Unresectable Stage IIIA/B Non-small Cell Lung Cancer

BACKGROUND: We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. METHODS: Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. RESULTS: Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). CONCLUSION: The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer

Combined QCD and electroweak analysis of HERA data

A simultaneous fit of parton distribution functions (PDFs) and electroweak parameters to HERA data on deep inelastic scattering is presented. The input data are the neutral current and charged current inclusive cross sections which were previously used in the QCD analysis leading to the HERAPDF2.0 PDFs. In addition, the polarisation of the electron beam was taken into account for the ZEUS data recorded between 2004 and 2007. Results on the vector and axial-vector couplings of the Z boson to u- and d-type quarks, on the value of the electroweak mixing angle and the mass of the W boson are presented. The values obtained for the electroweak parameters are in agreement with Standard Model predictions.Comment: 32 pages, 10 figures, accepted by Phys. Rev. D. Small corrections from proofing process and small change to Fig. 12 and Table

Limits on the effective quark radius from inclusive epep scattering at HERA

The high-precision HERA data allows searches up to TeV scales for Beyond the Standard Model contributions to electron-quark scattering. Combined measurements of the inclusive deep inelastic cross sections in neutral and charged current $ep$ scattering corresponding to a luminosity of around 1 fb$^{-1}$ have been used in this analysis. A new approach to the beyond the Standard Model analysis of the inclusive $ep$ data is presented; simultaneous fits of parton distribution functions together with contributions of "new physics" processes were performed. Results are presented considering a finite radius of quarks within the quark form-factor model. The resulting 95% C.L. upper limit on the effective quark radius is $0.43\cdot 10^{-16}$ cm.Comment: 10 pages, 4 figures, accepted by Phys. Lett.

Search for a narrow baryonic state decaying to pKS0{pK^0_S} and pˉKS0{\bar{p}K^0_S} in deep inelastic scattering at HERA

A search for a narrow baryonic state in the $pK^0_S$ and $\bar{p}K^0_S$ system has been performed in $ep$ collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb$^{-1}$ taken in 2003-2007. The search was performed with deep inelastic scattering events at an $ep$ centre-of-mass energy of 318 GeV for exchanged photon virtuality, $Q^2$, between 20 and 100 $\rm{} GeV^{2}$. Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb$^{-1}$ taken in 1996-2000, no resonance peak was found in the $p(\bar{p})K^0_S$ invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set.Comment: 16 pages, 4 figures, accepted by Phys. Lett. B. Minor changes from journal reviewing process, including a small correction to figure

A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma

BACKGROUND Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria ofthe European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS Of 193 patients who could be evaluated, 92 percent had been treated with three or more ofthe major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immuno-fixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy

Measurement of the cross-section ratio sigma_{psi(2S)}/sigma_{J/psi(1S)} in deep inelastic exclusive ep scattering at HERA

The exclusive deep inelastic electroproduction of $\psi(2S)$ and $J/\psi(1S)$ at an $ep$ centre-of-mass energy of 317 GeV has been studied with the ZEUS detector at HERA in the kinematic range $2 < Q^2 < 80$ GeV$^2$, $30 < W < 210$ GeV and $|t| < 1$ GeV$^2$, where $Q^2$ is the photon virtuality, $W$ is the photon-proton centre-of-mass energy and $t$ is the squared four-momentum transfer at the proton vertex. The data for $2 < Q^2 < 5$ GeV$^2$ were taken in the HERA I running period and correspond to an integrated luminosity of 114 pb$^{-1}$. The data for $5 < Q^2 < 80$ GeV$^2$ are from both HERA I and HERA II periods and correspond to an integrated luminosity of 468 pb$^{-1}$. The decay modes analysed were $\mu^+\mu^-$ and $J/\psi(1S) \,\pi^+\pi^-$ for the $\psi(2S)$ and $\mu^+\mu^-$ for the $J/\psi(1S)$. The cross-section ratio $\sigma_{\psi(2S)}/\sigma_{J/\psi(1S)}$ has been measured as a function of $Q^2, W$ and $t$. The results are compared to predictions of QCD-inspired models of exclusive vector-meson production.Comment: 24 pages, 8 figure

Shared Principles of Ethics for Infant and Young Child Nutrition in the Developing World

Abstract Background The defining event in the area of infant feeding is the aggressive marketing of infant formula in the developing world by transnational companies in the 1970s. This practice shattered the trust of the global health community in the private sector, culminated in a global boycott of Nestle products and has extended to distrust of all commercial efforts to improve infant and young child nutrition. The lack of trust is a key barrier along the critical path to optimal infant and young child nutrition in the developing world. Discussion To begin to bridge this gap in trust, we developed a set of shared principles based on the following ideals: Integrity; Solidarity; Justice; Equality; Partnership, cooperation, coordination, and communication; Responsible Activity; Sustainability; Transparency; Private enterprise and scale-up; and Fair trading and consumer choice. We hope these principles can serve as a platform on which various parties in the in the infant and young child nutrition arena, can begin a process of authentic trust-building that will ultimately result in coordinated efforts amongst parties. Summary A set of shared principles of ethics for infant and young child nutrition in the developing world could catalyze the scale-up of low cost, high quality, complementary foods for infants and young children, and eventually contribute to the eradication of infant and child malnutrition in the developing world

Measurement of neutral current e+/-p cross sections at high Bjorken x with the ZEUS detector

The neutral current e+/-p cross section has been measured up to values of Bjorken x of approximately 1 with the ZEUS detector at HERA using an integrated luminosity of 187 inv. pb of e-p and 142 inv. pb of e+p collisions at sqrt(s) = 318GeV. Differential cross sections in x and Q2, the exchanged boson virtuality, are presented for Q2 geq 725GeV2. An improved reconstruction method and greatly increased amount of data allows a finer binning in the high-x region of the neutral current cross section and leads to a measurement with much improved precision compared to a similar earlier analysis. The measurements are compared to Standard Model expectations based on a variety of recent parton distribution functions.Comment: 39 pages, 9 figure