CD4(+)CD25(+) regulatory T cells (Tregs) can promote the growth of some tumors, but it is unknown whether this is true for all tumors, including malignant pleural mesothelioma. We have previously shown that the existence of Tregs was associated with poor survival in patients with malignant pleural mesothelioma. In this study, using an intrathoracic murine model of malignant mesothelioma (MM), w...

The chemotherapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target in human leukemic cells, aminoimidazolecarboxamide ribonucleotide formyltransferase (AICART), the second folate-dependent enzyme of purine biosynthesis. The purine intermediate aminoimidazolecarboxamide ribonucleotide (ZMP), which accumulates behind this block, transmits an inhibitory s...

OBJECTIVE Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood-brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases. METHODS From January...

Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 -...

PURPOSE The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. PATIENTS AND METHODS Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received p...

PURPOSE Extramammary Paget's disease (EMPD) is a rare neoplasm with only a limited number of cases reported in the literature. Little was known about the availability of systemic chemotherapy for metastatic EMPD. METHODS We report one case of heavily pretreated EMPD with multiple organ metastases and successfully treated by pemetrexed. RESULT The tumor was progression after multi-line thera...

BACKGROUND Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus. METHODS We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC. RESULTS Eight patients were...

PURPOSE This report describes the data and analysis leading to the approval of pemetrexed (LY 231514, MTA, Alimta, Eli Lilly and Co., Indianapolis, IN) by the U.S. Food and Drug Administration (FDA) of a New Drug Application for the treatment of malignant pleural mesothelioma (MPM). EXPERIMENTAL DESIGN The FDA review of the efficacy and safety of pemetrexed assessed in a randomized clinical t...

Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx K(t) of 30 nM and V(max) of 10 nmol/g pr...

Pemetrexed is increasingly used in combination with platinum antineoplastic agents for the treatment of certain lung malignancies. Its use was associated with favorable hematological adverse reaction compared to standard regimens. Non-hematological life-threatening complications such as gastrointestinal perforations are extremely rare with pemetrexed use and tend to develop in the distal bowel ...