A Phase I, Dose Escalation Study of Oral ASP8273 in Patients with Non-small Cell Lung Cancers with Epidermal Growth Factor Receptor Mutations.

Acquired T790M mutations are the most frequently identified resistance mechanism to EGFR tyrosine kinase inhibitors (TKI) in patients with -mutant lung cancers. ASP8273 is a third-generation EGFR TKI with antitumor activity in preclinical models of EGFR-mutant lung cancer that targets mutant EGFR, including T790M. In this multicohort, phase I study (NCT02113813), escalating doses of ASP8273 (25-500 mg) were administered once daily to non-small cell lung cancer (NSCLC) patients with disease progression after prior treatment with an EGFR TKI.

BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer.

Purpose: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open-label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab.

Experimental Design: Treatment-naïve patients received mFOLFOX6 every 2 weeks of each 28-day cycle plus either tivozanib orally 1.

A multicenter phase II study of sepantronium bromide (YM155) plus rituximab in patients with relapsed aggressive B-cell Non-Hodgkin lymphoma.

This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.

Phase II, multicenter, open-label, randomized study of YM155 plus docetaxel as first-line treatment in patients with HER2-negative metastatic breast cancer.

The objective of this study was to assess the efficacy and tolerability of YM155, a survivin suppressor, in combination with docetaxel, compared with docetaxel alone in patients with HER2-negative metastatic breast cancer. This phase II, multicenter, open-label, 2-arm study randomized patients (≥18 years) with histologically or cytologically confirmed stage IV HER2-negative metastatic breast cancer and ≥1 measurable lesion, to receive docetaxel alone or docetaxel plus YM155. The primary endpoint was progression-free survival (PFS).

A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma.

Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel.

Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+)CD25(+) lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H).

Anti-VEGF Treatment of Corneal Neovascularization.

Vascular endothelial growth factor (VEGF) is an angiogenic factor shown to be a critical secreted cytokine in tumorigenesis and retinal neovascularization (NV). Currently, there are two anti-VEGF agents, pegaptanib and ranizumab, approved by the United States Food and Drug Administration (FDA) for intravitreal use in the treatment of wet age-related macular degeneration (AMD). Bevacizumab is FDA-approved for intravenous administration in the treatment of several cancers and is in widespread use, off-label, as an intravitreal injection to treat a variety of retinal pathologies.

A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma.

Background: Few effective therapeutic options exist for patients with refractory diffuse large B-cell lymphoma (DLBCL). YM155 is a survivin suppressant with activity against DLBCL in a phase I trial. This phase II study was conducted to better characterize the toxicity and efficacy of this small molecule in patients with refractory DLBCL.

Trichosporon asahii keratitis in a patient with a type I Boston keratoprosthesis and contact lens.

Purpose: The aim of the study was to report a case of Trichosporon asahii in a patient with a type I Boston keratoprosthesis and contact lens with review of the literature.

Methods: A case report and literature review are provided.

Results: A 70-year-old monocular South Asian man with light perception vision and dense corneal scarring from previously failed amniotic membrane grafting and one failed corneal transplant was evaluated for a keratoprosthesis for visual rehabilitation.

Corneal cross linking for keratoconus.

Riboflavin-induced ultraviolet light (UV) cross linking has received a significant amount of attention in recent years. It is currently approved in Europe as a treatment for keratoconus and is also being used for other corneal disorders. The goal of this paper is to review in detail seminal papers and studies that have been done to support cross linking as a safe and effective treatment for patients with early stages of keratoconus.

Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin.

Purpose: To determine the maximum-tolerated dose (MTD) and assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity of YM155, a small-molecule inhibitor of survivin.

Patients And Methods: Patients with advanced solid malignancies or lymphoma were treated with escalating doses of YM155 administered by 168-hour continuous intravenous infusion (CIVI). Plasma and urine samples were assayed to determine pharmacokinetic parameters and excretion.

Role of the transcriptional corepressor Bcor in embryonic stem cell differentiation and early embryonic development.

Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase.

Ziprasidone-associated mania: a review and report of 2 additional cases.

Although mania was not reported as an adverse event in the pivotal trials of ziprasidone, there have been 7 reports of ziprasidone-induced mania in 12 patients. We now report 2 additional cases wherein the introduction of ziprasidone resulted in new-onset manic episodes. In 1 case, the patient required hospitalization and lost his job.

Diplostomum spathaceum cercariae respond to a unique profile of cues during recognition of their fish host.

During its normal life cycle, Diplostomum spathaceum cercariae attach to and invade fish intermediate hosts. They are also known to attach to various other aquatic animals in response to water currents, touch and carbon dioxide. The purpose of this study was to identify the specific stimuli used by D.