Type B lactic acidosis: a rare oncological emergency.

Type B lactic acidosis is a rare metabolic complication of malignancy, more commonly in haematological malignancies. Due to the lack of formal prospective trials, treatment of lactic acidosis associated with malignancy is based on case reports. Given the poor prognosis, early recognition of type B lactic acidosis and prompt treatment are crucial.

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia.

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression.

Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia.

Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues.

Effectiveness of the extended parallel process model in promoting colorectal cancer screening.

Objective: Relatives of colorectal cancer (CRC) patients are at increased risk for the disease, yet screening rates still remain low. Guided by the Extended Parallel Process Model, we examined the impact of a personalized, remote risk communication intervention on behavioral intention and colonoscopy uptake in relatives of CRC patients, assessing the original additive model and an alternative model in which each theoretical construct contributes uniquely.

Methods: We collected intention-to-screen and medical record-verified colonoscopy information on 218 individuals who received the personalized intervention.

Epidermal growth factor receptor as a biomarker for cervical cancer.

This review focuses on the different modes of expression of the epidermal growth factor receptor (EGFR). All methods used to assess EGFR expression are critically analyzed and insights into the use of inhibitors of EGFR for treatment of cervical cancer are discussed. Currently, expression of EGFR as a biomarker for prognosis or for treatment of cervical cancer is not defined for clinical use.

Method of detection and breast cancer survival disparities in Hispanic women.

Background: Hispanic women in New Mexico (NM) are more likely than non-Hispanic women to die of breast cancer-related causes. We determined whether survival differences between Hispanic and non-Hispanic women might be attributable to the method of detection, an independent breast cancer prognostic factor in previous studies.

Methods: White women diagnosed with invasive breast cancer from 1995 through 2004 were identified from NM Surveillance Epidemiology End Results (SEER) files (n = 5,067) and matched to NM Mammography Project records.

Negotiating for success: navigating the contracting process for an exemplary research program.

Developing successful contracts is imperative for research sites conducting company-sponsored or investigator-initiated clinical trials. Good contracts help ensure sustainability and guide how research will be conducted.

The monoclonal antibody to cytotoxic T lymphocyte antigen 4, ipilimumab (MDX-010), a novel treatment strategy in cancer management.

Background: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory regulator of the T cell immune response against tumor cells. Ipilimumab (MDX-010) is a monoclonal antibody directed against CTLA-4.

Objective: To describe the basic mechanism of ipilimumab and discuss data available to date with regards to its safety and efficacy profile.

Are tanning beds "safe"? Human studies of melanoma.

Controversy continues over the carcinogenic properties of tanning beds. The tanning industry "sells" tanning beds as a safe alternative to UV exposure for both tanning as well as vitamin D biosynthesis. But, how safe are tanning beds? Epidemiologic data - incomplete and unsatisfactory - suggests that tanning beds are not safer than solar ultraviolet radiation and that they may have independent effects from solar exposure that increase risk for melanoma.

A phase I and pharmacokinetic study of paclitaxel poliglumex and cisplatin in patients with advanced solid tumors.

Purpose: Determine the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of paclitaxel poliglumex (PPX; CT-2103) in combination with cisplatin administered every 3 weeks.

Patients And Methods: Forty-three patients with advanced solid tumors were treated at escalating doses of PPX with a fixed dose of cisplatin at 75 mg/m(2). Conjugated and unconjugated paclitaxel were measured in plasma and urine.

Rate of thromboembolic events in mesothelioma.

Background: Thromboembolic event (TEE) rates in the general population and the cancer population are 0.1% to 2% and 10% to 15%, respectively. Our clinical observation is that mesothelioma patients are very susceptible to TEE, including arterial thromboses, but the TEE incidence has not been reported.

Genetic alterations determine chemotherapy resistance in childhood T-ALL: modelling in stage-specific cell lines and correlation with diagnostic patient samples.

Acquired drug resistance eventually leads to treatment failure in T-cell acute lymphoblastic leukaemia (T-ALL). Immunophenotypic and cytogenetic heterogeneities within T-ALL influence susceptibility to cytotoxic therapy, and little is known about the mechanisms of drug resistance at specific stages of T-cell ontogeny. We developed tolerance to therapeutic concentrations of daunorubicin (DNR) and L-asparaginase (L-asp) in Jurkat (CD1a(-), sCD3(+)) and Sup T1 (CD1a(+), sCD3(-)) cell lines, having respective 'mature' and 'cortical' stages of developmental arrest.

Capecitabine plus 3-weekly irinotecan (XELIRI regimen) as first-line chemotherapy for metastatic colorectal cancer: phase II trial results.

Background: Capecitabine results in superior response rate, improved safety, and improved convenience compared with 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (MCRC). Irinotecan in combination with 5-FU/LV has been shown to improve efficacy compared with 5-FU/LV alone in MCRC. Therefore, we evaluated the efficacy and safety of capecitabine plus irinotecan every 3 weeks (XELIRI regimen) as first-line treatment.

Regulation of N-formyl peptide receptor signaling and trafficking by individual carboxyl-terminal serine and threonine residues.

Adaptation, defined as the diminution of receptor signaling in the presence of continued or repeated stimulation, is critical to cellular function. G protein-coupled receptors (GPCRs) undergo multiple adaptive processes, including desensitization and internalization, through phosphorylation of cytoplasmic serine and threonine residues. However, the relative importance of individual and combined serine and threonine residues to these processes is not well understood.

Alternative administration of camptothecin analogues.

In order to improve the therapeutic index of camptothecin (CPT) analogues, alternative administration of CPT analogues is being evaluated. Topotecan, irinotecan, rubitecan, lurtotecan and 9-aminocamptothecin have been administered orally with response rates equivalent to that seen after intravenous administration, where applicable. Oral availability and administration of some of the newer CPT analogues, including diflomotecan (BN80915) and grimatecan (ST1481), have also shown promising results.

Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets.

The purpose of this article is to review the current literature pertaining to various angiogenic stimulators and angiogenesis inhibitors in gynecological malignancies and the relevance of these markers in the prognosis of these diseases. We also summarize the antiangiogenic drugs currently in development and in clinical use in gynecological oncology. The information was obtained from a computer search of MEDLINE for studies published in the English language regarding angiogenesis and angiogenesis inhibitors in gynecological malignancies between 1970 and December 2003; additional sources were identified through cross-referencing.

Flow cytometry for high-throughput, high-content screening.

Flow cytometry is a mature platform for quantitative multi-parameter measurement of cell fluorescence. Recent innovations allow up to 30-fold faster serial processing of bulk cell samples. Homogeneous discrimination of free and cell-bound fluorescent probe eliminates wash steps to streamline sample processing.

Mechanisms of G protein-coupled receptor-mediated degranulation.

Mast cells and neutrophils play a major role in the innate immune response. Following invasion of the host by microorganisms, these immune cells become activated and release anti-microbial cytotoxic granules in an effort to destroy invading microorganisms in a process termed degranulation. By-products from the degradation of microorganisms can also activate G-protein-coupled receptors (GPCRs), which can further activate immune cells.

Arrestins block G protein-coupled receptor-mediated apoptosis.

G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) activate numerous cellular signals through the combined actions of G proteins, GPCR kinases, and arrestins. Although arrestins have traditionally been thought of as mediating GPCR desensitization, they have now been shown to play important roles in the internalization, trafficking, and signaling of many GPCRs. We demonstrate that in cells devoid of arrestins, the stimulation of numerous GPCRs including the N-formyl peptide receptor (FPR) initiates rapid cell rounding, annexin V positivity, and caspase activation followed by cell death.

Changes in nonmelanoma skin cancer incidence between 1977-1978 and 1998-1999 in Northcentral New Mexico.

Nonmelanoma skin cancer (NMSC) is a highly common form of malignant disease in light-skinned populations. In 1977-1978, the National Cancer Institute sponsored a population-based skin cancer survey that found marked geographic variability in the incidence of NMSC within the United States. Some of the highest rates were observed in the southwestern state of New Mexico within its non-Hispanic white population.

N-formyl peptide receptors internalize but do not recycle in the absence of arrestins.

Arrestins mediate phosphorylation-dependent desensitization, internalization, and initiation of signaling cascades for the majority of G protein-coupled receptors (GPCRs). Many GPCRs undergo agonist-mediated internalization through arrestin-dependent mechanisms, wherein arrestin serves as an adapter between the receptor and endocytic proteins. To understand the role of arrestins in N-formyl peptide receptor (FPR) trafficking, we stably expressed the FPR in a mouse embryonic fibroblast cell line (MEF) that lacked endogenous arrestin 2 and arrestin 3 (arrestin-deficient).