Current Drugs News Results

Ask the doctor. I have tried all of the statin drugs to lower my cholesterol, but each one has caused severe muscle pain. Are there any non-statin medications I could try using to lower my cholesterol?

Harv Heart Lett. 2010 Aug; 20(12): 8
Lee T

Clinical syndromes and consequences of antiretroviral-related hepatotoxicity.

Hepatology. 2010 Sep; 52(3): 1143-55
Núñez M

Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates the management of patients infected with human immunodeficiency virus (HIV), increases medical costs, alters the prescription patterns, and affects the guideline recommendations. Among the clinical consequences derived from HAART-related liver toxicity, hypersensitivity reactions and lactic acidosis are recognized as acute events with potential to evolve into fatal cases, whereas there seems to be other syndromes not as well characterized but of equal concern as possible long-term liver complications. Belonging to the latter category of syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal hypertension, and nodular regenerative hyperplasia are discussed in this review. Updated information on liver toxicity of current antiretroviral drugs, including the most recently licensed, is provided. Management and prevention of liver toxicity among HIV-infected patients treated with HAART are reviewed as well. (HEPATOLOGY 2010;52:1143-1155).

Enhanced spectrophotometric determination of two antihyperlipidemic mixtures containing ezetimibe in pharmaceutical preparations.

Drug Test Anal. 2010 Sep 1;
Maher HM, Youssef RM, Hassan EM, El-Kimary EI, Barary MA

Two spectrophotometric methods are presented for the simultaneous determination of ezetimibe/simvastatin and ezetimibe/atorvastatin binary mixtures in combined pharmaceutical dosage forms without prior separation. The first is the derivative ratio method where the amplitudes of the first derivative of the ratio spectra ((1)DD) at 299.5 and 242.5 nm were found to be linear with ezetimibe and simvastatin concentrations in the ranges 0.5-20 microgml(-1) and 1-40 microgml(-1), respectively, whereas the amplitudes of the first derivative of the ratio spectra ((1)DD) at 289.5 and 288 nm were selected to determine ezetimibe and atorvastatin in the concentration ranges 5-50 microgml(-1) and 1-40 microgml(-1), respectively. The second is the H-point standard additions method; absorbances at the two pairs of wavelengths, 228 and 242 nm or 238 and 248 nm, were monitored while adding standard solutions of ezetimibe or simvastatin, respectively. For the analysis of ezetimibe/atorvastatin mixture, absorbance values at 226 and 248 nm or 212 and 272 nm were monitored while adding standard solutions of ezetimibe or atorvastatin, respectively. Moreover, differential spectrophotometry was applied for the determination of ezetimibe in the two mixtures without any interference from the co-existing drug. This was performed by measurement of the difference absorptivities (DeltaA) of ezetimibe in 0.07 M 30% methanolic NaOH relative to that of an equimolar solution in 0.07 M 30% methanolic HCl at 246 nm. The described methods are simple, rapid, precise and accurate for the determination of these combinations in synthetic mixtures and dosage forms. Copyright (c) 2010 John Wiley & Sons, Ltd.

Simultaneous spectrophotometric determination of chlordiazepoxide and clidinium using multivariate calibration techniques.

Drug Test Anal. 2010 Sep 1;
Khoshayand MR, Abdollahi H, Moeini A, Shamsaie A, Ghaffari A, Abbasian S

Three multivariate modelling approaches including partial least squares regression (PLS), genetic algorithm-partial least squares regression (GA-PLS), and principal components-artificial neural network (PC-ANN) analysis were investigated for their application to the simultaneous determination of chlordiazepoxide and clidinium levels in pharmaceuticals. A set of synthetic mixtures of drugs in ethanol and 0.1 M HCL was made, and the prediction abilities of the aforementioned methods were examined using RSE% (relative standard error of the prediction). The PLS and PC-ANN methods were found to be comparable, and GA-PLS produced slightly better results. The predictive models that we built were successfully applied to simultaneously determine the levels of chlordiazepoxide and clidinium in coated tablets. Copyright (c) 2010 John Wiley & Sons, Ltd.

Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley rats.

Phytother Res. 2010 Sep; 24(9): 1347-53
Park CM, Cha YS, Youn HJ, Cho CW, Song YS

The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl(4)) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl(4) control, and two DLWE groups (0.5 and 2 g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl(4) (50% CCl(4)/olive oil; 0.5 mL/kg bw) was administered 24 h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl(4)-induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl(4) administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl(4) were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl(4)-induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl(4). Copyright (c) 2010 John Wiley & Sons, Ltd.

Lived and perceived of their profession by Togolese doctors.

Tunis Med. 2010 Sep; 88(9): 660-5
Viwale Koffi-Tessio A, Oniankitan O, Mijiyawa M

Aim: a study has been carried out by Togolese medical doctors in order to determine the perceived and the real life of their profession. Methods: the study, which was transversal, has taken in account a sample of 52 medical doctors made on the basis of a cautious choice. Most of these medical doctors (15 general practitioners, 23 specialists and 14 hospitalouniversitaires) work in the medical cares centres of Lomé. A sheet of survey has permitted the collection of demographic datas and datas relating to the medical studies and carreer. Results: the 52 medical doctors included in the study (7 women, 45 men) were between 25 and 59 years old; their age of getting their A-level was between 16 and 23 years old, and that of getting the doctorate diploma between 24 and 37. The length of professional experience stands between 8 months and 27 years. The marital status was specified by 47 of the 52 medical doctors: 13 single, one divorced, and 33 married; 5 of the 7 women who took part in the survey were single and without any child. The love of the profession (65%), the social status it confers (37%) and the honour tied to the profession (27%) were the main motives of choosing the profession. The decision of doing medical studies was taken during secondary studies by 45 of the 52 persons. The faculty of medicine of Lomé has been the study frame to general medicine studies of 35 persons (67%). The low payment (83%), the poverty of the patients (83%), the narrowness of the technical platform (79%), the insufficiency of cares structures in paramedical personnel (67%), the insufficiency of continuing education (60%), and the lack or insufficiency of drugs (58%) were the main problems encountered during their professional experience by the people questioned. 22 medical doctors (43%) have estimated that their profession has given them a particular social status. Only 8 medical doctors have found that the real things they have gone trough in the profession matches with the idea they had, while 32 (62%) are ready to choose again the profession if they have to start everything. The little time spent with the family has been stated out by 36 medical doctors (69%), the social and family prestige that came out of it by 32 (62%), and the ability to control the health of one's family by 34 (65%). The psychological impact of the profession on the medical doctors questioned was dominated by the adoption of a philosophical attitude towards life. Conclusion: a better productivity of the Togolese medical doctors needs the improvement of their life conditions (adjustment of texts in force, revision of the salary scale), the renovation of the facilities, the modernization of the technical platform, the continuing education of the medical doctors and the reinforcement of the practical management of the patient on bed.

Mechanisms of distribution and targeting of neuronal ion channels.

Curr Opin Drug Discov Devel. 2010 Sep; 13(5): 559-67
Thayer DA, Jan LY

The discovery and development of pharmaceutical drugs targeting ion channels is important for treating a variety of medical conditions and diseases. Ion channels are expressed ubiquitously throughout the body, and are involved in many basic physiological processes. Neuronal ion channels are particularly appealing drug targets, and recent advances in screening ion channel function using optical-based and electrophysiological technologies have improved drug development in this field. Moreover, methods for the discovery of peptide-based neurotoxins and other natural products have proven useful in the pharmacological assessment of ion channel structure and function, while also contributing to the identification of lead molecules for drug development.

Emerging targets for hematological malignancies.

Curr Opin Drug Discov Devel. 2010 Sep; 13(5): 548-58
Cilloni D, Frassoni F, Saglio G

Molecularly targeted therapies have been increasingly incorporated into standard treatment regimens for the majority of hematological malignancies. To increase the efficacy of the next generation of drugs, research efforts have been aimed at identifying molecular defects specific to leukemic cells. A significant therapeutic opportunity is represented by the possibility of selectively eradicating the leukemic stem cell pool. This review focuses on new insights regarding oncogenetic mechanisms in hematological malignancies and related possible druggable targets, including the pathways leading to leukemic stem cell maintenance and the specific approaches used to eliminate them.

Modulation of the vasopressin system for the treatment of CNS diseases.

Curr Opin Drug Discov Devel. 2010 Sep; 13(5): 538-47
Ryckmans T

Vasopressin (also known as arginine vasopressin [AVP]) is a small cyclic peptide that acts at the V1a, V1b and V2 GPCRs to regulate a wide range of physiological functions, including vasoconstriction, smooth muscle contractility, response to stress, and excretion of water and sodium via the kidney. The potential therapeutic applications of AVP receptor ligands have prompted significant interest in this target within the pharmaceutical research community, and several small-molecule drugs targeting the AVP receptor have reached the market, mainly for cardiovascular indications. The development of AVP receptor modulators for the treatment of CNS indications has proven more challenging, and is the focus of this review. The regulatory role of AVP on the hypothalamic-pituitary-adrenal (HPA) axis suggests potential uses for AVP receptor modulators in various CNS indications, including depression, anxiety and post-traumatic stress disorder. Several clinical trials of V1a and V1b receptor antagonists in CNS indications have been conducted, but none of these drugs have reached the market. In recent years, the discovery of the key role of AVP in modulating complex social behaviors has provided a unique opportunity to understand the physiological mechanisms of social interactions. Ultimately, the ongoing research in this field may enable the development of treatments to alleviate the social deficits associated with conditions such as autism and schizophrenia. Given the large unmet medical need in these areas, a renewed interest in the field of CNS-penetrant AVP receptors modulators is expected.

Who Are the Opinion Leaders? The Physicians, Pharmacists, Patients, and Direct-to-Consumer Prescription Drug Advertising.

J Health Commun. 2010 Sep; 15(6): 629-55
Lee AL

A popular perception holds that physicians prescribe requested drugs to patients influenced by mass mediated direct-to-consumer prescription drug advertising. The phenomenon poses a serious challenge to the two-step flow model, which emphasizes the influence of opinion leaders on their followers and their legitimating power over the informing power of the mass media. This study investigates a 2002 Food and Drug Administration (FDA) survey and finds that patients searching for drug information through mass and hybrid media in newspapers and magazines' small print, the Internet, and toll-free numbers are more likely to seek information through interpersonal communication channels like health care providers. Patients using small print, toll-free numbers, one's own physician, and other physicians are associated with influencing their physicians with various drug-requesting behaviors. But physicians only prescribe requested drugs to patients who are influenced by other health care providers, such as pharmacists and other physicians, not the mass media. The influence of expert opinion leaders of drugs is so strong that the patients even would switch from their own unyielding physicians who do not prescribe drugs as advised by the pharmacists. Physicians and patients all are influenced more by other expert opinion leaders of drugs than by the mass media and therefore still uphold the basic tenet of the two-step model.

Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.

Eur J Clin Pharmacol. 2010 Sep 2;
Cao YB, Zhang JD, Shen H, Jiang YY

PURPOSE: Rivaroxaban is a newly developed oral medicine that direct inhibits factor Xa for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the efficacy and safety of rivaroxaban versus enoxaparin, a medicine routinely used for thromboprophylaxis after total hip or knee arthroplasty. METHODS: We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome for our meta-analysis was total venous thromboembolism (VTE) and all-cause mortality. The primary safety outcome was bleeding events, which were categorized as major, clinically relevant non-major, or minor events. RESULTS: Eight RCTs, involving 15,586 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with rivaroxaban was associated with significantly fewer VTE and all-cause mortality [9,244 patients, risk ratio (RR) 0.56, 95% confidence interval (CI) 0.39-0.80] cases and a similar incidence of bleeding cases (major bleeding events: 13,384 patients, RR 1.65, 95% CI 0.93-2.93; clinically relevant non-major bleeding events: 13,384 patients, RR 1.21, 95% CI 0.98-1.50; total bleeding events, 13,384 patients, RR 1.10, 95% CI 0.97-1.24). The total hip or knee arthroplasty subgroup analysis revealed consistent efficacy and safety findings. CONCLUSIONS: Rivaroxaban was more effective than the recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty.

How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis.

Osteoporos Int. 2010 Sep 2;
Marie PJ, Felsenberg D, Brandi ML

Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption exceeding formation), results in impaired bone architecture, mass and strength. Current anti-osteoporotic drugs act on bone remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the concept of inducing opposite effects on bone resorption and formation. One therapeutic agent, strontium ranelate, was shown to induce opposite effects on bone resorption and formation in pre-clinical studies and to reduce fracture risk in postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone strength in humans remains a matter of debate, however. This review of the most recent pre-clinical and clinical studies is a critical analysis of strontium ranelate's action on bone resorption and formation and how it increases bone mass, microarchitecture and strength in postmenopausal osteoporotic women.

MAP Kinase Regulation of the Mitotic Spindle Checkpoint.

Methods Mol Biol. 2010; 661: 497-505
Eves EM, Rosner MR

Maintaining the integrity of the cell cycle is critical for ensuring that cells only undergo DNA replication and proliferation under controlled conditions in response to discrete stimuli. One mechanism by which the fidelity of this process is guaranteed is through the activation of cell cycle checkpoints. The mitotic spindle checkpoint, which is regulated by Aurora B kinase, ensures proper kinetochore attachment to chromosomes leading to equal distribution of chromosomes to daughter cells. We demonstrated that the mitogen-activated protein kinase (MAPK) cascade regulates mitotic progression and the spindle checkpoint. As demonstrated by immunofluorescence at kinetochores, depletion of Raf Kinase Inhibitory Protein (RKIP), an inhibitor of Raf/MEK/ERK signaling, causes an increase in MAPK activity that inhibits Aurora B kinase activity. By monitoring mitotic index and transit time from nuclear envelope breakdown to anaphase, we demonstrated that RKIP depletion leads to a defective spindle checkpoint and genomic instability, particularly in response to drugs that disrupt microtubule function.

Analysis of ERKs' Dimerization by Electrophoresis.

Methods Mol Biol. 2010; 661: 335-42
Pinto A, Crespo P

Signals transmitted by ERK MAP Kinases regulate the functions of multiple substrates present in the nucleus and the cytoplasm. Once phosphorylated, ERKs dimerize. The functions of these dimers had remained elusive until recently when we demonstrated that ERK dimers are assembled using scaffolds proteins as platforms. Dimerization is critical for connecting the scaffolded ERK complex to cognate cytoplasmic substrates. Contrarily, nuclear substrates associate to ERK monomers. These results identify dimerization as a key determinant of the spatial specificity of ERK signals. Moreover, we showed that preventing ERK dimerization, without affecting ERK phosphorylation, is sufficient for attenuating cellular proliferation, transformation, and tumor development. Thus, analyzing ERK dimerization will be an important factor in the future for determining, for example, the real impact on the ERK pathway of some drugs that do not affect ERK phosphorylation. Herein, we describe user-friendly methods for such purpose.

Assessment of Pediatric asthma drug use in three European countries; a TEDDY study.

Eur J Pediatr. 2010 Sep 2;
Sen EF, Verhamme KM, Neubert A, Hsia Y, Murray M, Felisi M, Giaquinto C, 't Jong GW, Picelli G, Baraldi E, Nicolosi A, Ceci A, Wong IC, Sturkenboom MC,

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ss2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ss2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ss2-mimetics (the UK highest). Off-label use was low, and most pronounced for ss2-mimetics in children <18 months (IT) and combined ss2-mimetics + anticholinergics in children <6 years (NL). Conclusion: This study shows that among all asthma drugs, ss2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety.

The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients.

Intensive Care Med. 2010 Sep 2;
Boerma EC, Ince C

PURPOSE: The clinical use of vasoactive drugs is not only intended to improve systemic hemodynamic variables, but ultimately to attenuate derangements in organ perfusion and oxygenation during shock. This review aims (1) to discuss basic physiology with respect to manipulating vascular tone and its effect on the microcirculation, and (2) to provide an overview of available clinical data on the relation between vasoactive drugs and organ perfusion, with specific attention paid to recent developments that have enabled direct in vivo observation of the microcirculation and concepts that have originated from it. METHODS: A MedLine search was conducted for clinical articles in the English language over the last 15 years pertainig to shock, sepsis, organ failure, or critically ill patients in combination with vasoactive drugs and specific variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance, laser Doppler, and sidestream dark field imaging). RESULTS: Eighty original papers evaluating the specific relationship between organ perfusion/oxygenation and the use of vasoactive drugs were identified and are discussed in light of physiological theory of vasomotor tone. CONCLUSIONS: Solid clinical data in support of the idea that increasing blood pressure in shock improves microcirculatory perfusion/oxygenation seem to be lacking, and such a concept might not be in line with physiological theory of microcirculation as a low-pressure vascular compartment. In septic shock no beneficial effect on microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been reported, but a wide range in inter-individual effect seems to exist. Whether improvement of microcirculatory perfusion is associated with better patient outcome remains to be elucidated.

Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated primary mixed glial cell culture.

Naunyn Schmiedebergs Arch Pharmacol. 2010 Sep 2;
Bielecka AM, Paul-Samojedny M, Obuchowicz E

An increasing body of evidence indicates that glial activation and neuroinflammation play an important role in the pathogenesis of psychiatric and neurodegenerative diseases. Activated glial cells secrete various cytokines that influence neurotransmission, hypothalamus-pituitary-adrenal axis activity, neuronal plasticity and neurogenesis. It has been suggested that alterations in cytokine networks are involved in the mechanism of action of antidepressant drugs. Until now, only a few studies demonstrated that some tricyclic antidepressants and selective serotonin reuptake inhibitors reduced production of pro-inflammatory cytokines in brain glia cells. We have investigated for the first time whether the antidepressant, moclobemide (a reversible selective inhibitor of monoamine oxidase-A) has an influence on pro-inflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha] and anti-inflammatory cytokine (IL-10) in primary rat mixed glial cell cultures stimulated by lipopolysaccharide (LPS). Our results showed that moclobemide used in a wide range of concentrations diminished LPS-stimulated IL-1beta and TNF-alpha mRNAs expression in cellular extracts and remarkably reduced the levels of both pro-inflammatory cytokines in culture medium. In opposite to this, the drug had no influence on IL-10 mRNA and slightly reduced IL-10 concentration. Moreover, moclobemide decreased LPS-stimulated translocation of NFkappaB p65 subunit into cellular nuclei. These results suggest that moclobemide exerts anti-inflammatory effect in the central nervous system because it affects the balance between pro- and anti-inflammatory cytokines (IL-1beta, TNF-alpha/IL-10) in primary mixed glial cell cultures.

[Regional anesthesia and neurological diseases.]

Anaesthesist. 2010 Sep 2;
Sinner B, Graf BM

Modern anesthesia is handling an increasing number of patients with neurological diseases who require narcosis. Regional anesthesia techniques offer qualities which might be advantageous for this group particularly for childbirth. The number of pregnant women with neurological diseases has increased significantly in the recent years due to improved diagnostics and therapy. A more careful approach to regional anesthesia in patients with neurological diseases is necessary as the drugs themselves possess neurotoxic effects and the procedure might worsen the underlying neurological diseases. Additionally, performing regional anesthesia might be more complicated and the resulting blockade might be different from the expected neuronal block. Published data concerning regional anesthesia in this patient group are limited and mainly restricted to case reports. In this review general considerations regarding regional anesthesia, techniques, drugs and methods in these patient groups will be discussed. In the second part the practical approach to regional anesthesia for some of the most important neurological diseases is highlighted.

In vitro novel combinations of psychotropics and anti-cancer modalities in U87 human glioblastoma cells.

Int J Oncol. 2010 Oct; 37(4): 1043-51
Tzadok S, Beery E, Israeli M, Uziel O, Lahav M, Fenig E, Gil-Ad I, Weizman A, Nordenberg J

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor. Despite some recent improvement in the treatment of this malignancy, life expectancy of GBM patients remains extremely low. Therefore, continuous efforts to develop new treatment modalities are mandatory. A novel approach to cancer treatment is the use of targeted treatments, alone and in combination with other therapies. In this study, we evaluated the effects of novel combinations of conventional anti-cancer treatments (temozolomide or irradiation) with the targeted drug, imatinib, or with psychotropic drugs, belonging to the selective serotonin reuptake inhibitors (SSRIs) and phenothiazine subclasses, as well as combination of imatinib with psychotropic agents, on a human U87 glioblastoma cell line. The combination of temozolomide with imatinib or the psychotropic drugs resulted in an additive anti-proliferative effect, while the combination of irradiation and the psychotropic agents resulted in a less than additive effect on cell proliferation. A marked synergistic anti-proliferative effect of imatinib combined with the psychotropic drugs fluoxetine, sertraline or perphenazine was demonstrated. None of the single or combined treatments led to a reduction in the expression of phosphorylated MAP kinase. However, a marked synergistic reduction in the expression of the key regulatory molecule, pAKT, was detected, following the combined treatment of the cells with the imatinib/psychotropics combination. This down-regulation of pAKT may mediate the synergistic anti-proliferative interaction of imatinib with the psychotropic agents. Although the concentrations of the psychotropic agents used in this and other in vitro studies were beyond the clinically relevant blood levels in humans, recent studies have demonstrated anti-proliferative effects in vivo, using sertraline in a human colon cancer model. Thus, it seems that further in vivo studies combining imatinib with psychotropic agents, especially fluoxetine and sertraline, are warranted.

Involvement of C12orf32 overexpression in breast carcinogenesis.

Int J Oncol. 2010 Oct; 37(4): 861-7
Kim JW, Fukukawa C, Ueda K, Nishidate T, Katagiri T, Nakamura Y

Through genome-wide gene expression profile analysis of breast cancer, we identified a gene, chromosome 12 open reading frame 32 (C12orf32), to be involved in mammary carcinogenesis. Semiquantitative RT-PCR and Northern blot analysis confirmed C12orf32 overexpression in breast cancer cells and its almost undetectable level of expression in normal human tissues. Immunocytochemical staining analysis using breast cancer cell lines revealed a cell cycle-dependent subcellular localization of endogenous C12orf32 protein. Depletion of C12orf32 expression by small-hairpin RNA interference significantly suppressed the growth of breast cancer cell lines possibly due to the inhibition of G1/S transition and subsequent cell death. Western blot analysis indicated that a C12orf32 protein of 35 kDa predicted from the cDNA sequences was processed to a 16-kDa protein of (C12orf32-p16) which was accumulated in most of breast cancer cell lines examined. Our data suggest that C12orf32 is a promising molecular target for the development of novel anticancer drugs such as peptide vaccines and siRNA drugs.