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UNLABELLED Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non-small cell lung cancer. This therapy(More)
In the early 1950s and 1960s, peritoneal dialysis (PD) was used primarily to treat patients with acute renal failure. Continuous ambulatory peritoneal dialysis (CAPD) was introduced in 1976 and continues to gain popularity as an effective method of renal replacement therapy for patients with end-stage renal disease (ESRD). The PD catheter is inserted into(More)
Bcl-2 is a central regulator of cell survival that is overexpressed in the majority of small cell lung cancers (SCLC) and contributes to both malignant transformation and therapeutic resistance. We compared primary SCLC xenografts prepared from de novo human tumors with standard cell line-based xenografts in the evaluation of a novel and highly potent small(More)
BACKGROUND AT-101 is an oral inhibitor of the antiapoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and an inducer of the pro-apoptotic proteins noxa and puma. We studied the efficacy of AT-101 in patients with recurrent chemosensitive extensive-stage small cell lung cancer (SCLC). METHODS Patients with recurrent "sensitive" SCLC (defined as no(More)
New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies. We explored the combination of ABT-737 and(More)
New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through(More)
A large fraction of non-small cell lung cancers (NSCLC) are dependent on defined oncogenic driver mutations. Although targeted agents exist for EGFR- and EML4-ALK-driven NSCLCs, no therapies target the most frequently found driver mutation, KRAS. Furthermore, acquired resistance to the currently targetable driver mutations is nearly universally observed.(More)
OBJECTIVE To determine the current prevalence of erythromycin resistance and penicillin tolerance of group A beta-hemolytic streptococci (GABHS) in Japan. RESEARCH DESIGN One hundred four isolates of GABHS from the civilian community in Tokyo and 101 isolates from the military population at the US Air Force Base in Yokota, Japan, were tested for(More)
The cases of 4 patients with clinical signs of intraocular large cell lymphoma are described. Initial cytopathologic examination of vitrectomy specimens failed to establish the malignant character of the vitreous infiltrates. Three of the four patients eventually developed solid central nervous system tumors, intracranial biopsy samples of which revealed(More)