Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors.

Purpose: This phase I study evaluated the feasibility, safety, pharmacokinetics (PK), and preliminary evidence of anticancer activity of the sequential administration of paclitaxel and trabectedin on an every-2-week schedule in patients with refractory solid malignancies. The study also sought to determine the maximum tolerated dose (MTD) level on this schedule, as well as to recommend doses for disease-directed studies.

Experimental Design: Twenty-seven patients were treated with paclitaxel (80-120 mg/m(2); 1-hour i.

Prostate cancer in African-American men and polymorphism in the calcium-sensing receptor.

Background: Prospective epidemiologic studies indicate that the risk for advanced prostate cancer is increased among men with high levels of serum calcium. Because serum calcium levels are influenced by the calcium-sensing receptor (CaSR), we examined prostate cancer in African-American men in relation to three single nucleotide polymorphisms (SNPs) in the CaSR gene, A986S, R990G and Q1011E. This is the first study of CaSR polymorphisms and risk of prostate cancer.

Spirituality and Cultural Identification Among Latino and Non-Latino College Students.

The purposes of this study were to examine (a) differences in spiritual perspectives and practices of Latino and non-Latino young adults and (b) the cultural relevance of the Latino Spiritual Perspective Scale (LSPS). Studies indicate that spiritual perspectives are embedded within cultural group norms and vary significantly across ethnic groups. A cross-sectional survey design was used with a convenience sample of 223 Latino and non-Latino university students in the Southwestern United States.

An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption.

Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors.

C-reactive Protein among Community-Dwelling Hypertensives on Single-agent Antihypertensive Treatment.

Background: C-reactive protein is a predictor of adverse cardiovascular outcomes. The effect of antihypertensive therapy on C-reactive protein levels is largely unknown.

Method: We undertook a cross-sectional study of CRP levels among participants with primary hypertension on single-agent anti-hypertensive therapy in the community-based biracial Genetic Epidemiology Network of Arteriopathy cohort.

Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase.

Checkpoint kinase 1 (Chk1) regulates cell cycle checkpoints and DNA damage repair in response to genotoxic stress. Inhibition of Chk1 is an emerging strategy for potentiating the cytotoxicity of chemotherapeutic drugs. Here, we demonstrate that AZD7762, an ATP -competitive Chk1/2 inhibitor induces gammaH2AX in gemcitabine-treated cells by altering both dynamics and stability of replication forks, allowing the firing of suppressed replication origins as measured by DNA fiber combing and causing a dramatic increase in DNA breaks as measured by comet assay.

Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival.

Background: : Ipilimumab is a monoclonal antibody that antagonizes cytotoxic T lymphocyte antigen-4, a negative regulator of the immune system. The authors report on advanced refractory melanoma patients treated in a compassionate use trial of ipilimumab at the Memorial Sloan-Kettering Cancer Center.

Methods: : Patients with advanced refractory melanoma were treated in a compassionate use trial with ipilimumab 10 mg/kg every 3 weeks for 4 doses.

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

Purpose: Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial.

Patients And Methods: Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily.

Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1.

Fyn null mice display reduced adiposity associated with increased fatty acid oxidation, energy expenditure, and activation of the AMP-dependent protein kinase (AMPK) in skeletal muscle and adipose tissue. The acute pharmacological inhibition of Fyn kinase activity with SU6656 in wild-type mice reproduces these metabolic effects and induced a specific reduction in fat mass with no change in lean mass. LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was redistributed from the nucleus into the cytoplasm of cells treated with SU6656 and in cells expressing a kinase-deficient, but not a constitutively kinase-active, Fyn mutant.

Ifosfamide may be safely used in patients with end stage renal disease on hemodialysis.

Background. Pharmacokinetic data on clearance of ifosfamide in hemodialysis patients are limited. Consequently, these patients are excluded from therapy with this agent.

Robotic brachytherapy and sublobar resection for T1 non-small cell lung cancer in high-risk patients.

Background: Sublobar lung resection and brachytherapy seed placement is gaining acceptance for T1 non-small cell lung cancer (NSCLC) in select patients with comorbidities precluding lobectomy. Our institution first reported utilization of the da Vinci system for robotic brachytherapy developed experimentally in swine and applied to high-risk patients 5 years ago. We now report seed dosimetrics and midterm follow-up.

"Life history space": a multivariate analysis of life history variation in extant and extinct Malagasy lemurs.

Studies of primate life history variation are constrained by the fact that all large-bodied extant primates are haplorhines. However, large-bodied strepsirrhines recently existed. If we can extract life history information from their skeletons, these species can contribute to our understanding of primate life history variation.

Dental development and life history in living African and Asian apes.

Life-history inference is an important aim of paleoprimatology, but life histories cannot be discerned directly from the fossil record. Among extant primates, the timing of many life-history attributes is correlated with the age at emergence of the first permanent molar (M1), which can therefore serve as a means to directly compare the life histories of fossil and extant species. To date, M1 emergence ages exist for only a small fraction of extant primate species and consist primarily of data from captive individuals, which may show accelerated dental eruption compared with free-living individuals.

Comparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide.

Office, home, and ambulatory blood pressure (BP) demonstrate variable associations with outcomes. The authors sought to compare office BP (OBP), home BP (HBP), and ambulatory BP (ABP) for measuring responses to hydrochlorothiazide (HCTZ), atenolol, and their combination. After completing washout, eligible patients were randomized to atenolol 50 mg or HCTZ 12.

Obstructive sleep apnea and aldosterone.

Background: Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects.

Hypothalamic nutrient sensing in the control of energy homeostasis.

The hypothalamus is a center of convergence and integration of multiple nutrient-related signals. It can sense changes in circulating adiposity hormones, gastric hormones and nutrients, and receives neuroanatomical projections from other nutrient sensors, mainly within the brainstem. The hypothalamus also integrates these signals with various cognitive forebrain-descending information and reward/motivation-related signals coming from the midbrain-dopamine system, to coordinate neuroendocrine, behavioral and metabolic effectors of energy balance.

Brainstem integrative function in the central nervous system control of food intake.

The caudal brainstem lies at a critical nexus in the neural hierarchy that helps determine the negative feedback control of ingestion. It is the first central nervous system site that receives neural input from vagal and nonvagal visceral afferents that convey not only meal-related signals from postoral sites reflecting chemical, mechanical and nutrient properties of ingested foods, but also responses to nutrient stimulated peptides and neurotransmitters via extrinsic gut afferent receptors. In addition, the circumventricular area postrema (AP) affords the caudal brainstem access to circulating factors that are released during a meal, as well as to adiposity hormones that reflect the availability of stored nutrients.

Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors.

Purpose: Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil (5FU)-induced apoptosis in a sequence-dependent manner.

Experimental Design: We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors.

The relation of serum parathyroid hormone and serum calcium to serum levels of prostate-specific antigen: a population-based study.

Experimental and clinical data implicate calcium and parathyroid hormone (PTH) in the development of prostate cancer. However, epidemiologic data on the role of these variables in prostate health are sparse. We examined the relationship between serum levels of calcium, PTH, and prostate-specific antigen (PSA), an established marker of prostate growth, in a large, population-based study using multivariate linear regression.

Serum calcium levels are elevated among women with untreated postmenopausal breast cancer.

Objective: Reports of an association between primary hyperparathyroidism in women and risk of breast cancer suggest an etiologic role for high serum calcium. However, data on the association between serum calcium levels and breast cancer in women without clinical hyperparathyroidism are limited.

Methods: We conducted a hospital-based case-control study among postmenopausal women in Fargo, ND.

Autophagy regulates adipose mass and differentiation in mice.

The relative balance between the quantity of white and brown adipose tissue can profoundly affect lipid storage and whole-body energy homeostasis. However, the mechanisms regulating the formation, expansion, and interconversion of these 2 distinct types of fat remain unknown. Recently, the lysosomal degradative pathway of macroautophagy has been identified as a regulator of cellular differentiation, suggesting that autophagy may modulate this process in adipocytes.

Uncommon etiology of an anterior chest wall mass.

A rare but important constellation of musculoskeletal and cutaneous symptoms, including synovitis, acne, pustulosis, hyperostosis, and osteitis, has recently been designated the SAPHO syndrome. The exact etiology is unknown, although various infectious agents have been proposed. The most common site of osteoarticular involvement is the sternoclavicular joint, and therefore, recognition of this syndrome and appropriate workup and management is crucial in the differential diagnosis of an anterior chest wall mass.

Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents.

Purpose: Pharmacokinetic/pharmacodynamic (PK/PD) models have been shown to be useful in predicting tumor growth rates in mouse xenografts. We applied novel PK/PD models to the published anticancer combination therapies of tumor growth inhibition to simulate synergistic changes in tumor growth rates. The parameters from the PK/PD model were further used to estimate clinical doses of the combination.

Isolated bladder metastasis causing large bowel obstruction: a case report of an atypical presentation of intussusception.

Intussusception of the large bowel is a rare clinical entity. In adults, this pathology is usually associated with a malignant lead point and often requires operative management. Reported is the case of an 83-year-old female who was recently diagnosed with superficial bladder cancer (T1) treated by partial cystectomy.

Lack of correlation between thiazide-induced hyperglycemia and hypokalemia: subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.

Study Objective: To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients.

Design: Prespecified subgroup analysis of results from a prospective, multicenter, randomized, open-label, parallel-group study. Setting.