International variation in prostate cancer incidence and mortality rates.

Context: Wide variation exists internationally for prostate cancer (PCa) rates due to differences in detection practices, treatment, and lifestyle and genetic factors.

Objective: We present contemporary variations in PCa incidence and mortality patterns across five continents using the most recent data from the International Agency for Research on Cancer.

Evidence Acquisition: PCa incidence and mortality estimates for 2008 from GLOBOCAN are presented.

Cancer burden in Africa and opportunities for prevention.

Cancer is an emerging public health problem in Africa. About 715,000 new cancer cases and 542,000 cancer deaths occurred in 2008 on the continent, with these numbers expected to double in the next 20 years simply because of the aging and growth of the population. Furthermore, cancers such as lung, female breast, and prostate cancers are diagnosed at much higher frequencies than in the past because of changes in lifestyle factors and detection practices associated with urbanization and economic development.

International trends in liver cancer incidence rates.

Background: Several previous studies have documented region or country-specific liver cancer incidence trends around the world. However, no study has systematically examined the international pattern using the most recently updated incidence data from the International Agency for Research on Cancer.

Methods: We examined recent trends in liver cancer incidence rates from 1993 to 2002 by joinpoint analysis for 32 cancer registries worldwide, using Cancer Incidence in Five Continents.

Changes in smoking prevalence among U.S. adults by state and region: Estimates from the Tobacco Use Supplement to the Current Population Survey, 1992-2007.

Background: Tobacco control policies at the state level have been a critical impetus for reduction in smoking prevalence. We examine the association between recent changes in smoking prevalence and state-specific tobacco control policies and activities in the entire U.S.

Global cancer statistics.

The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.

Global patterns of cancer incidence and mortality rates and trends.

While incidence and mortality rates for most cancers (including lung, colorectum, female breast, and prostate) are decreasing in the United States and many other western countries, they are increasing in several less developed and economically transitioning countries because of adoption of unhealthy western lifestyles such as smoking and physical inactivity and consumption of calorie-dense food. Indeed, the rates for lung and colon cancers in a few of these countries have already surpassed those in the United States and other western countries. Most developing countries also continue to be disproportionately affected by cancers related to infectious agents, such as cervix, liver, and stomach cancers.

The convergence of lung cancer rates between blacks and whites under the age of 40, United States.

Lung cancer rates in the United States have been consistently higher in blacks than in whites at all ages in men and at younger ages in women. However, since the 1970s, smoking initiation decreased more rapidly among blacks than whites. We examined trends in lung cancer rates for white and black young adults (ages 20-39) from 1992 to 2006 using joinpoint models and black-to-white rate ratios by sex.

The global burden of cancer: priorities for prevention.

Despite decreases in the cancer death rates in high-resource countries, such as the USA, the number of cancer cases and deaths is projected to more than double worldwide over the next 20-40 years. Cancer is now the third leading cause of death, with >12 million new cases and 7.6 million cancer deaths estimated to have occurred globally in 2007.

Worldwide variations in colorectal cancer.

Previous studies have documented significant international variations in colorectal cancer rates. However, these studies were limited because they were based on old data or examined only incidence or mortality data. In this article, the colorectal cancer burden and patterns worldwide are described using the most recently updated cancer incidence and mortality data available from the International Agency for Research on Cancer (IARC).

International trends in colorectal cancer incidence rates.

Background: Previous studies have documented significant variations in colorectal cancer incidence rates and trends regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the IARC.

Methods: We obtained sex-specific colorectal cancer incidence for 1953-57 through 1998-2002 by cancer registry from Cancer Incidence in Five Continents (CI5) databases.

Cancer occurrence.

In this chapter, we describe the variability of cancer occurrence by using measures of incidence, mortality, prevalence, and survival, according to demographic characteristics such as age, sex, socioeconomic status, and race/ethnicity, as well as geographic location and time period. We also discuss the variability of cancer occurrence in relation to changes in risk factors, screening rates, and improved treatments. The variation according to risk factors provides strong evidence that much of cancer is caused by environmental factors and is potentially avoidable.

Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control.

Background: The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report includes trends in lung cancer incidence and death rates, tobacco use, and tobacco control by state of residence.

Methods: Information on invasive cancers was obtained from the NCI, CDC, and NAACCR and information on mortality from the CDC's National Center for Health Statistics.

Mutagenesis of the putative nucleotide-binding domains of the multidrug resistance associated protein (MRP). Analysis of the effect of these mutations on MRP mediated drug resistance and transport.

Studies were conducted to examine the functional role of the nucleotide-binding domains of MRP in drug resistance and drug transport in isolated membrane vesicles. In vivo studies were conducted by preparing stable transfectants of HeLa cells with wild-type MRP cDNA or MRP cDNAs which had been mutated at certain nucleotide binding domains (NBD). Stable transfectants producing equivalent amounts of the MRP encoded protein P190 were used in this study.

Multidrug resistance-associated protein (MRP) mediated transport of daunomycin and leukotriene C4 (LTC4) in isolated plasma membrane vesicles.

Studies have been carried out to examine in vitro drug transport in plasma membrane vesicles isolated from HL60/ADR cells that overexpress MRP. The results demonstrate that glutathione (GSH) enhances transport of daunomycin. A greater increase in transport activity occurs when the reaction is carried out in the presence of both GSH and sodium chloride.

Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells.

Two membrane glycoproteins acting as energy-dependent efflux pumps, mdr-encoded P-glycoprotein (P-gp) and the more recently described multidrug resistance-associated protein (MRP), are known to confer cellular resistance to many cytotoxic hydrophobic drugs. In the brain, P-gp has been shown to be expressed specifically in the capillary endothelial cells forming the blood-brain barrier, but localization of MRP has not been well characterized yet. Using RT-PCR and immunoblot analysis, we have compared the expression of P-gp and Mrp1 in homogenates, isolated capillaries, primary cultured endothelial cells, and RBE4 immortalized endothelial cells from rat brain.

Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42.

Variants of the human ovarian carcinoma cell line, OAW42, exhibiting low-level intrinsic resistance (OAW42-SR) and drug-induced higher-level resistance (OAW42-A1 & OAW42-A), were studied along with a sensitive clonal population (OAW42-S) which was isolated from OAW42-SR. Expression of the MDR-associated protein P-170, the more recently discovered LRP (lung resistance-related protein) and MRP (multidrug resistance-associated protein), topoisomerase II alpha and beta, GST pi and the cytoskeletal proteins, cytokeratin 8 and vimentin, were studied (using immunocytochemistry and Western blotting techniques) in conjunction with drug (doxorubicin) accumulation and subcellular distribution. Expression of mRNA for P-170, MRP, topoisomerase 11 alpha and beta and GST pi was studied using RT-PCR (reverse transcriptase polymerase chain reaction).

Functional analysis of the nucleotide binding domains of the multidrug resistance protein (MRP).

HeLa cells were transfected with full-length multidrug resistance protein (MRP) cDNA and with MRP cDNAs that had been mutated at certain nucleotide binding domains. Stable transfectants were isolated and those producing equivalent amounts of P190 were tested in cytotoxicity assays using a variety of chemotherapeutic agents. The results demonstrate that deletions in the C-motif of NBD1 or the A-motif of NBD2 have a pronounced effect in reducing resistance levels to adriamycin, vincristine, or etoposide (VP-16).

ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump.

We have previously shown that the multidrug resistance protein (MRP) mediates the ATP-dependent membrane transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) and of structurally related anionic conjugates of lipophilic compounds [Jedlitschky, Leier, Buchholz, Center and Keppler (1994) Cancer Res. 54, 4833-4836; Leier, Jedlitschky, Buchholz, Cole, Deeley and Keppler (1994) J. Biol.

Evidence that SP1 modulates transcriptional activity of the multidrug resistance-associated protein gene.

In previous studies, we have cloned and sequenced a 5'-end region of the multidrug resistance-associated protein (MRP) gene that contains promoter activity as assessed through transient transfections of constructs contained in a pCAT basic reporter plasmid. In the present study, using a series of deletion mutants, evidence was obtained that the SP1 binding sites contained in the promoter are essential for optimal MRP transcriptional activity. These results were supported by the finding that introduction of site-specific mutations into the wild-type SP1 sequence produced a major reduction in CAT activity.

Expression and characterization of the multidrug resistance-associated protein in insect cells infected with a recombinant baculovirus.

The protein encoded by the multidrug resistance-associated protein (MRP) gene was examined after infection of SF21 insect cells with recombinant baculovirus containing a full-length MRP cDNA. The time course of appearance of the protein as determined by western blot analysis revealed that maximum levels occurred 2 days postinfection. The amount of MRP made in this system was somewhat variable, but levels that were about 4-fold greater than that found in HL60/ADR cells could be achieved.

Phosphorylation of the multidrug resistance associated protein gene encoded protein P190.

Recent studies suggest that multidrug resistance of HL60/ADR cells is related to an overexpression of the MRP (multidrug resistance associated protein) gene which encodes a 190-kDa ATP-binding membrane glycoprotein. In the present study we have further characterized P190 and have examined phosphorylation properties of the protein. The results demonstrate that P190 is highly phosphorylated and that the phosphate groups are metabolically active and undergo cycles of phosphorylation and dephosphorylation in the cell.

ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein.

The ATP-dependent transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) was more than 25-fold higher in membrane vesicles prepared from human leukemia cells (HL60/ADR) overexpressing the multidrug resistance-associated protein than from drug-sensitive parental HL60 cells or revertant cells. Similar results were obtained with S-(2,4-dinitrophenyl)glutathione as substrate. Photoaffinity labeling detected preferentially in the HL60/ADR membranes a 190-kilodalton protein binding [3H]LTC4 and 8-azido[alpha-32P]ATP.

Cloning and sequence analysis of the promoter region of the MRP gene of HL60 cells isolated for resistance to adriamycin.

Non-P-glycoprotein multidrug resistance of HL60/ADR cells appears to be related to overexpression of the MRP gene. Recent studies suggest that this gene may play an important role in a new form of cell resistance to certain chemotherapeutic agents. To examine mechanisms regulating transcriptional activity of this gene, a 2.

Analysis of MRP gene expression and function in HL60 cells isolated for resistance to adriamycin.

In an effort to define clearly the basis of non-P-glycoprotein multidrug resistance in HL60/ADR cells, we have analyzed expression of MRP mRNA levels and the MRP-encoded protein in resistant cells and also in resistant cells that have undergone a reversion to drug sensitivity. The results demonstrate that an MRP cDNA containing 5'-end coding sequences reacts with a 6-kb RNA, which is overexpressed in the resistant isolate. As resistant cells revert to drug sensitivity there is essentially a complete loss of the 6-kb RNA.

The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein.

HL60 cells isolated for resistance to Adriamycin (HL60/ADR) overexpress a 190-kDa ATP binding protein which has a minor sequence homology with P-glycoprotein. It has also been observed that HL60/ADR overexpress the MRP gene which was first identified as a component of a non-P-glycoprotein mediated multidrug resistance of H69/ADR cells [Cole et al., Science (Washington DC), 258: 1650, 1992].