Ibrutinib as a bridge to transplant in high-risk chronic lymphocytic leukemia: A case report and review of the literature.

The treatment landscape of chronic lymphocytic leukemia (CLL) has been challenged by the advent of novel classes of drugs, such as B-cell receptor (BCR)-inhibitors and BCL-2 antagonists. In selected high-risk patients, the choice to start allogeneic hematopoietic stem cell transplantation (alloHCT) or continue these agents is a matter of debate. Furthermore, published data about the impact on the feasibility of alloHCT and the optimal timing of administration are limited.

Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6).

The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs.

Environmental and biological monitoring of benzene in traffic policemen, police drivers and rural outdoor male workers.

To evaluate exposure to benzene in urban and rural areas, an investigation into personal exposure to benzene in traffic policemen, police drivers and rural (roadmen) male outdoor workers was carried out. Personal samples and data acquired using fixed monitoring stations located in different areas of the city were used to measure personal exposure to benzene in 62 non-smoker traffic policemen, 22 police drivers and 57 roadmen. Blood benzene, urinary trans-trans muconic acid (t,t-MA) and S-phenyl-mercapturic acid (S-PMA) were measured at the end of work shift in 62 non-smoker traffic policemen, 22 police drivers and 57 roadmen and 34 smoker traffic policemen, 21 police drivers and 53 roadmen.

Schedule-dependent apoptosis in K-ras mutant non-small-cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separation.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) given concurrently with chemotherapy in 4 large randomized clinical trials did not improve patient outcomes compared with chemotherapy alone in advanced non-small-cell lung cancer (NSCLC). We hypothesized that the lack of benefit resulted from a negative interaction between chemotherapy and EGFR TKIs.

Materials And Methods: Herein, we report the cell cycle and apoptotic effects of treatment with erlotinib and docetaxel in the NSCLC cell lines A549 and Calu-1, both of which are mutant for K-ras and wild-type for EGFR.

The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study.

Introduction: Bortezomib is a small-molecule proteasome inhibitor with single-agent activity in patients with non-small cell lung carcinoma (NSCLC) and synergy with gemcitabine in preclinical studies. The combination of gemcitabine and carboplatin is an accepted first-line treatment for advanced NSCLC. We conducted a phase I study of gemcitabine and carboplatin in combination with bortezomib.

Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer.

Introduction: Bortezomib and pemetrexed are approved anticancer agents with non-overlapping mechanisms of action and toxicity. We examined the safety and tolerability of pemetrexed in combination with two different schedules of bortezomib in patients with advanced solid tumors.

Methods: Two separate dose-escalating arms (arm A and arm B) were conducted simultaneously.

Incorporating bortezomib into the treatment of lung cancer.

Bortezomib, a small-molecule proteasome inhibitor, has activity in lung cancer both as a single agent and in combination with agents commonly used in lung cancer. The ability of bortezomib to favorably modulate the expression of apoptosis-associated proteins, along with its moderate toxicity as a single agent, provides the basis for its combination with cytotoxic agents in the treatment of lung cancer. In non-small cell lung cancer, bortezomib as a single agent has limited activity but in combination with chemotherapy has shown encouraging activity without significantly adding to toxicity.

Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study.

Background: Erlotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule assembly inhibiting mitosis during metaphase. Both drugs are commonly used as single agents in the treatment of advanced non small cell lung cancer (NSCLC).

Pharmacodynamic separation of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy in non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced-stage non-small-cell lung cancer (NSCLC). One potential explanation for this lack of benefit is a negative interaction or antagonism between chemotherapy and EGFR TKIs when delivered concomitantly. Support for this line of reasoning is provided by preclinical data demonstrating that EGFR TKIs induce primarily a cytostatic effect resulting from a G1 cell cycle arrest in cell lines with wild-type EGFR, reducing cell cycle phase-dependent activity of chemotherapy, whereas they induce apoptotic cell death in tumors with EGFR-activating mutations.

Bortezomib-based combinations in the treatment of non-small-cell lung cancer.

Lung cancer is the most common cause of cancer-related death among men and women in the United States. Current trials are focusing on the integration of novel therapeutic agents into current non-small-cell lung cancer (NSCLC) treatment paradigms. Bortezomib, a small-molecule proteasome inhibitor, has single-agent activity in NSCLC and in combination with agents commonly used in NSCLC.

Predictive molecular markers: has the time come for routine use in lung cancer?

Although some evidence exists to support the use of clinical factors such as performance status and weight loss to predict response and toxicity to therapy in non-small cell lung cancer (NSCLC) patients, researchers have shown little prospective data on the use of molecular markers to facilitate selection of specific chemotherapy or new molecularly targeted agents in this patient population. Breast cancer exemplifies the growing role that molecular markers are playing, not only as prognostic factors, but also in predicting response to targeted treatments such as hormonal therapy, and more recently, trastuzumab (Herceptin). Although several studies have examined molecular markers in lung cancer and have shown promising potential value, these studies were retrospective and require prospective validation.

Docetaxel in non-small cell lung cancer: a review.

Docetaxel (Taxotere, Aventis Pharma), a semisynthetic taxane targeting the beta-subunit of tubulin, has broad spectrum anticancer activity including non-small cell lung cancer (NSCLC). It is synergistic with platinum and radiation in preclinical models and has been tested clinically in every stage of NSCLC. Docetaxel-platinum combinations have an efficacy comparable to other newer-agent platinum doublets as first-line therapy in advanced NSCLC, and has been approved for use in this setting.