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nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients.In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile.Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy.nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.

Myeloid-derived suppressor cells (MDSCs) represent a heterogenous collection of immature myeloid cells endowed with suppressive function on the immune response. Their presence has been extensively investigated in preclinical models, especially in the context of cancer. One of the major obstacles in their accurate identification has been the definition of an unambiguous phenotype, shared between mice and humans, and clearly correlating with their suppressive function. In this paper, we review the literature concerning the phenotype in mouse and in humans, showing that at least 2 subsets of MDSCs are present under different situations. We also address the role of MDSCs in tumor progression, evaluate the prognostic significance of MDSC in cancer patients, and their possible role as marker of clinical outcome and response to therapy. Finally, we examine the strategies designed to modulate MDSCs in cancer patients, which might represent an innovative approach to enhance the effectiveness of immune-based therapies.

Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%.

Objective— Cyclooxygenase-2 (COX-2) and interferon γ (IFNγ) are overexpressed in vascular inflammatory and atherosclerotic lesions. We postulated that IFNγ suppresses COX-2 expression at the transcriptional level. Methods and Results— The effect of IFNγ on COX-2 expression was evaluated in several types of human cells stimulated with phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1β, or tumor necrosis factor (TNF) α. IFNγ concentration-dependently inhibited COX-2 proteins and promoter activities induced by PMA or cytokines in human fibroblasts and monocytic and endothelial cells. PMA and cytokines stimulate binding of C-Jun, C-Fos, CCAAT/enhancer binding protein β (C/EBPβ), or NF-κB to their respective regulatory elements on COX-2 promoter. IFNγ blocked C-Jun and C/EBPβ but not C-Fos or p50 NF-κB binding as determined by in vitro binding assays and chromatin immunoprecipitation assay. p300 binding to COX-2 promoter was inhibited by IFNγ in a manner comparable to C-Jun and C/EBPβ binding. Conclusions— IFNγ suppresses proinflammatory mediator-induced COX-2 transcription by selective inhibition of C-Jun and C/EBPβ DNA binding activity and p300 recruitment in human cells. Because IFNγ is coexpressed with COX-2 in vascular lesions, it may play a role in controlling COX-2–mediated inflammatory changes.