Rapid Inhibitor Discovery by Exploiting Synthetic Lethality.

Synthetic lethality occurs when inactivation of two genes is lethal but inactivation of either single gene is not. This phenomenon provides an opportunity for efficient compound discovery. Using differential growth screens, one can identify biologically active compounds that selectively inhibit proteins within the synthetic lethal network of any inactivated gene.

Expanding mandatory healthcare personnel immunization beyond influenza: Impact of a broad immunization program with enhanced accountability.

Objective: Evaluation of a mandatory immunization program to increase and sustain high immunization coverage for healthcare personnel (HCP).

Design: Descriptive study with before-and-after analysis.

Setting: Tertiary-care academic medical center.

SPANOL (SPectral ANalysis of Lobes): A Spectral Clustering Framework for Individual and Group Parcellation of Cortical Surfaces in Lobes.

Understanding the link between structure, function and development in the brain is a key topic in neuroimaging that benefits from the tremendous progress of multi-modal MRI and its computational analysis. It implies, , to be able to parcellate the brain volume or cortical surface into biologically relevant regions. These parcellations may be inferred from existing atlases (e.

A phase II trial of pemetrexed and gemcitabine in patients with metastatic breast cancer who have received prior taxane therapy.

Purpose: This phase II trial assessed efficacy and safety of pemetrexed plus gemcitabine to treat metastatic or locally advanced breast cancer in patients previously treated with taxanes.

Patients And Methods: Eligible women with advanced breast cancer treated with taxanes in the adjuvant or metastatic setting received pemetrexed 500 mg/m2 on day 1 followed by gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Hematologic toxicities limiting day 8 gemcitabine dosing were observed in the first 20 patients, prompting a protocol amendment to evaluate pemetrexed 500 mg/m2 followed by gemcitabine 1500 mg/m2 on day 1 of a 14-day cycle.

Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.

Objectives: Gemcitabine (G) plus cisplatin (C) is standard care for metastatic transitional cell carcinoma (TCC) of the urothelium. Pemetrexed (P), alone or in combination with G, is active in metastatic TCC. However, the safety and efficacy of P combined with GC therapy is unknown.

An open-label pilot study of pentostatin, mitoxantrone, and rituximab in patients with previously untreated, Stage III or IV, low-grade non-Hodgkin lymphoma.

Background: In a previous study, the authors demonstrated that the combination of pentostatin (P) and rituximab (R) was well tolerated and was active in patients with low-grade non-Hodgkin lymphoma (NHL). In the current study, mitoxantrone (M) was added to P + R to evaluate the toxicity and efficacy of this three-drug combination (PMR).

Methods: Twenty-four previously untreated patients with histologically proven, Stage III or IV, low-grade NHL were registered between April and September, 2002.

Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

Background: Among patients diagnosed with advanced non-small-cell lung carcinoma (NSCLC), African-Americans have lower survival rates than non-African-Americans. Whether this difference is due to innate characteristics of the disease in the two ethnicities or to disparities in health care is not known. We investigated whether the disparity in survival would persist when patients were treated with similar systemic therapies (i.

Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study.

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation.

Nonoperative management of non-small cell lung cancer: the current cancer and leukemia group B experience.

The Cancer and Leukemia Group B (CALGB) is studying nonoperative management in two subgroups of patients with advanced non-small cell lung cancer. In patients with regional disease, primarily those with bulky N2 or T4 disease or those with contralateral mediastinal involvement (N3), a phase III trial is under way to explore concurrent carboplatin as intensification of local therapy and additional systemic treatment. This builds on prior CALGB work demonstrating the benefits of induction chemotherapy prior to radiation for selected patients with stage III disease.

Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose chemotherapy.

We utilized mobilized peripheral blood stem cells (PBSC) as sole support for hematologic reconstitution following high-dose chemotherapy in 52 patients with advanced solid tumors and lymphoma. PBSC were collected by large scale leukapheresis after mobilization with chemotherapy. Each apheresis product was analysed for total nucleated cells, CFU-GM and CD34+ content.

An evaluation of the susceptibility patterns of gram-negative organisms isolated in cancer centres with aminoglycoside usage.

This study in 12 cancer treatment centres across the United States was designed to evaluate the potential for increased resistance to amikacin with unrestricted use. An initial 3-month baseline period during which the use of amikacin was restricted and that of tobramycin and gentamicin unrestricted was followed by a period of at least 12 months when amikacin was the primary aminoglycoside. Resistance of Gram-negative bacilli to these aminoglycosides from hospitalized patients was monitored and compared for the two periods.

Phase I clinical evaluation of cytarabine and cisplatin in patients with advanced cancer.

Studies in cell culture systems and tumor-bearing animals have demonstrated synergistic cytotoxicity of cytarabine (ara-C) and cisplatin. We have conducted a phase I trial to assess the toxic effects and tolerable doses of these drugs in patients with advanced cancer. Forty-five such patients were treated with varying dosages of ara-C infused continuously during Days 1-3 of a 28-day cycle.

Sperm phagocytosis by human peritoneal macrophages: a possible cause of infertility in endometriosis.

The mechanism of infertility in women with endometriosis is unknown, but it is independent of mechanical factors that affect fallopian tube function. Increased numbers of peritoneal macrophages are present in women with endometriosis and have access to the female reproductive tract via the oviducts. To determine whether peritoneal macrophages might phagocytize sperm and thereby contribute to infertility in women with endometriosis, we examined peritoneal macrophages from 32 fertile and infertile women; the infertile group was separated into those with and those without visible endometriosis.

Treatment of small cell carcinoma of the lung with methotrexate, doxorubicin, cyclophosphamide, and lomustine: a community-based study.

Forty-four patients with undifferentiated small cell carcinoma of the lung (SCCL) were diagnosed and treated at community hospitals. Patients with limited disease were treated with surgical resection or primary radiation therapy (RT) followed by chemotherapy; those with extensive disease received chemotherapy followed by RT if there was not a complete primary response. The chemotherapy used was a combination of methotrexate, doxorubicin, cyclophosphamide, and lomustine.

Monocyte chemotactic peptide receptor. Functional characteristics and ligand-induced regulation.

Monocytes, macrophages, and neutrophils will demonstrate several important cellular functions in response to synthetic formylated oligopeptides. N-formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-lysine (fNLPNTL) was a potent chemoattractant for human blood monocytes; a 1.0-nM concentration induced a maximal chemotactic response.