We report a series of patients with pancreatic metastasis treated with sunitinib.

Materials and Methods: We retrospectively studied a population of 15 adults with pancreatic metastasis of renal cell carcinoma at 1 center in France and at 2 in the United States who were treated with sunitinib between 2005 and Nutlin-3a cost 2007. Sunitinib monotherapy was given at a dose of 50 mg orally in 6-week cycles, consisting of 4 weeks of treatment followed by 2 weeks of rest. All clinical and radiological data were analyzed.

Results: At a median followup of 20 months

the overall tumor response using Response Evaluation Criteria in Solid Tumors was 34%. Median time to relapse was 20 months. Two deaths were noted and median survival was not attained. Responses in the pancreatic metastasis were seen in 28% of patients and were stable in 72%. The main grade 3 and 4 adverse events were diarrhea in 7% of cases and fatigue in 7%. Only grade 1 increased lipase was noted. in 27% of patients and no increase in amylase was noted.

Conclusions: Sunitinib is effective in patients with pancreatic metastasis. This raises the question

PCI-32765 molecular weight of whether patients with metastatic renal cell carcinoma limited to the pancreas may derive greater clinical benefit from anti-angiogenic agents, rather than from aggressive surgical resection. However, surgery remains the only potential cure in patients with

isolated AMP deaminase pancreatic metastasis.”
“The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states. There is good evidence for a prominent alpha(2)-adrenoceptor-mediated inhibitory system and 5-HT(3) (and likely also 5-HT(2)) serotonin receptor-mediated excitatory controls originating from brainstem and midbrain areas. The ability of cortical controls to influence spinal function allows for top-down processing through these monoamines. The links between pain and the comorbidities of sleep problems, anxiety, and depression may be due to the dual roles of noradrenaline and of 5-HT in these functions and also in pain. These controls appear, in the cases of peripheral neuropathy, spinal injury, and cancer-induced bone pain to be driven by altered peripheral and spinal neuronal processes; in opioid-induced hyperalgesia, however, the same changes occur without any pathophysiological peripheral process. Thus, in generalized pain states in which fatigue, mood changes, and diffuse pain occur, such as fibromyalgia and irritable bowel syndrome, one could suggest an abnormal engagement of descending facilitations with or without reduced inhibitions but with central origins. This would be an endogenous central malfunction of top-down processing, with the altered monoamine systems underlying the observed symptoms.

In contrast, pre-training or pre-test NPS injections were ineffective, suggesting that NPS had no Daporinad solubility dmso effect on IA

memory acquisition or recall. Peripheral administration of a synthetic NPSR antagonist attenuated NPS-induced IA memory enhancement, showing pharmacological specificity. NPS also enhanced hippocampal-dependent non-aversive memory in the novel object recognition task. In contrast, NPSR knockout mice displayed deficits in IA memory, novel object recognition, and novel place or context recognition, suggesting that activity of the endogenous NPS system is required for memory formation. Blockade of adrenergic signaling by propranolol attenuated NPS-induced memory enhancement in the IA task, indicating involvement of central MK1775 noradrenergic systems. These results provide evidence for a facilitatory role of NPS in long-term memory, independent of memory content, possibly by acting as a salience signal or as an arousal-promoting factor. Neuropsychopharmacology

(2011) 36, 744-752; doi:10.1038/npp.2010.207; published online 8 December 2010″
“Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3(-/-) female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3(-/-) mice. Female AC3(-/-) mice failed the pup retrieval Sinomenine assay, did not construct well-defined nests, and did not exhibit maternal aggression.

Furthermore, AC3(-/-) females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3(-/-) female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3(-)/(-) female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE. Neuropsychopharmacology (2011) 36, 772-781; doi:10.1038/npp.2010.211; published online 8 December 2010″
“Chronic methamphetamine (meth) abuse can lead to persisting cognitive deficits. Here, we utilized a long-access meth self-administration (SA) protocol to assess recognition memory and metabotropic glutamate receptor (mGluR) expression, and the possible reversal of cognitive impairments with the mGluR5 allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB). Male, Long-Evans rats self-administered i.v. meth (0.02 mg/infusion) on an schedule of reinforcement or received yoked-saline infusions.

in this study, we measured functional magnetic resonance imaging signals to investigate how frontal cortex activities

change corresponding to JAK inhibitor subjects’ performance as they tried to lose (successfully inhibiting the typical response to win) when presented with a gesture signifying rock, paper, or scissors. Performance rates ranged from 50% to 100%, and results indicated that activation in the bilateral anterior part of the prefrontal cortex increased parametrically corresponding to subjects’ successful performance. This result implies that the anterior prefrontal cortex plays a key role in the successful completion of a modified RPS task and may play a role in the suppression of stereotyped responses. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Temperature affects growth rate of crocodiles. However, no information exists about the effects of temperature by El Nino-South Oscillation (ENSO) on crocodiles. In this paper, we present information about the effect of ENSO on total length and body Nutlin-3a cost mass of Crocodylus acutus in captivity during 1997-2001. We did not observe differences in total length among years, but we did so

in body mass. Furthermore, we observed that warm episodes of ENSO were associated with a higher average total length and cold episodes represented a higher average of body mass. Sea surface temperature (SST) was significantly related with total length; however, the relationship between SST and body mass was unclear. We suggest that ENSO effects on growth rates of crocodiles need to be considered as an important factor on the management of captive populations. (C) 2008 Elsevier Ltd. All rights reserved.”
“High levels of calcium-independent phospholipase A(2) (iPLA(2)) are present in the striatum and cerebral cortex [W.Y. Ong, J.F Yeo, S.F. Ling, A.A. Farooqui, Distribution of calcium-independent

phospholipase A(2) (iPLA(2)) Venetoclax chemical structure in monkey brain, J. Neurocytol. 34 (2005) 447-458], and several clinical investigations have suggested a possible role of altered iPLA(2) activity in neurodegenerative and psychiatric disorders. The present study was carried out to elucidate a possible effect of PLA(2) on prepulse inhibition (PPI) of the acoustic startle reflex. Rats that received intraperitoneal injection of the non-specific PLA(2) inhibitor, quinacrine, showed significantly decreased PPI at 76,80, and 84 dB, compared to saline injected controls. In addition, rats that received intrastriatal injection of antisense oligonucleotide to iPLA(2) showed significant reduction in PPI at prepulse intensities of 76 and 84 dB compared to scrambled sense injected controls. Together, these findings point to a role of PLA(2) in PPI of the auditory startle reflex and sensorimotor gating. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Hormesis in longevity is a widespread phenomenon across the animal kingdom.

The future challenge is to understand how inactivation of such central players or of their upstream regulators or downstream effectors can affect adipose tissue in a depot-specific fashion”
“Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical

targets to treat Cilengitide molecular weight binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping EX 527 cost of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like

drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence. Neuropsychopharmacology (2012) 37, 1409-1421; doi: 10.1038/npp.2011.327; published online 4 January 2012″
“Little is known on both the

composition and mechanism(s) of proteinuria Janus kinase (JAK) associated with the use of mTOR inhibitors, in particular of Everolimus (E). We characterized urinary proteins utilizing an integrated proteomics approach (quantitative essays, 2-DE, MALDI-TOF, Western blot) in 48 renal transplant recipients who were alternatively treated with E (n = 31) or with enteric coated mycophenolic acid (EC-MPA) (n = 17). Twelve E patients (39%) developed high (>3 g/day) or intermediate proteinuria (1-3 g) compared to four (23%) of the EC-MPA group. Urinary proteins (p<0.001), 02 microglobulin (p<0.001) and alpha 1microglobulin (P<0.025) were higher in E than in EC-MPA, appeared more rapidly and were inversely correlated with the day of treatment.

Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus, understanding how altered serotonin signaling affects neuronal morphology and plasticity, and ultimately animal physiology and pathophysiology, will be of great significance.”
“Despite evidence that high-affinity GABA(A) receptor subunit mRNA and protein are present VEGFR inhibitor in dorsal root ganglia (DRG), low-affinity currents dominate those detected in acutely dissociated

DRG neurons in vitro. This observation raises the possibility that high-affinity receptors are normally trafficked out of the DRG toward central and peripheral terminals. We therefore hypothesized that with time in culture, there would be an increase in high-affinity GABA(A) currents in DRG neurons. To test this hypothesis, we studied dissociated DRG neurons 2 check details h (acute) and 24 h (cultured) after plating with whole-cell patch-clamp techniques, Western blot, and semiquantitative reverse transcriptase polymerase chain reaction (sqRT-PCR) analysis. GABAA

current density increases dramatically with time in culture in association with the emergence of two persistent currents with EC50′s of 0.25 +/- 0.01 mu M and 3.2 +/- 0.02 mu M for GABA activation. In a subpopulation of neurons, there was also an increase in the potency of GABA activation of the transient current from an EC50 of 78.16 +/- 10.1 mu M to 9.56 +/- 1.3 mu M with time in culture. A

fraction of the high-affinity current was potentiated by delta-subunit agonist 4,5,6,7-tetrahydroisozazolo[5,4-c]pyridine-3-ol (THIP). delta-subunit immunoreactivity was largely restricted to the cytosolic fraction Megestrol Acetate in acute, but the membrane fraction in cultured, DRG neurons, with no detectable change in delta-subunit mRNA. However, the emergence of a high-affinity current blocked by THIP and insensitive to bicuculline was detected in a subpopulation of cultured neurons as well in association with an increase in rho(2)- and rho(3)-subunit mRNA in cultured DRG neurons. Our results suggest that high-affinity delta-subunit-containing GABA(A) receptors are normally trafficked out of the DRG where they are targeted to peripheral and central processes. They also highlight that the interpretation of data obtained from cultured DRG neurons should be made with caution. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We studied modulation of the P300 by monetary reward expected to be received on a sustained attention task in 18 individuals with current cocaine use disorders (CUD) and 18 control subjects. Results in the controls revealed sensitivity to money as measured with P300 amplitude and speed of behavioral response and their intercorrelations.

These circuits provide a potential neural basis for observed positive associations between anger-out and pain responsiveness. The role of endogenous opioids in modulating activity in these interlinked brain regions is explored, and implications for understanding pain-related effects of anger-out are described.

An opioid dysfunction hypothesis is presented in which inadequate endogenous opioid inhibitory activity in these brain regions contributes to links between trait anger-out and pain. A series of studies is presented that supports the opioid dysfunction hypothesis, further suggesting that gender and genetic factors may moderate these effects. Finally, possible implications of interactions between trait anger-out and state behavioral anger expression on endogenous opioid analgesic activity are described. (c) 2009 Elsevier Selleckchem CP673451 Ltd. All rights reserved.”
“Objectives. Except for compression therapy, physical therapy has scarcely been evaluated in the treatment of chronic venous disorders (CVD). Spa treatment is a popular way to administer physical therapy for CVD in France, but its efficacy has not been evaluated yet. SGC-CBP30 purchase This study aimed to assess the efficacy

of balneotherapy associated with patient education, as performed in the spa resort of La Lechere, in patients with advanced chronic venous insufficiency (CEAP clinical classes C4/C5).

Methods. The study was a randomized controlled trial, spa therapy being administered on top of the usual LY294002 medical care. Evaluation was by a blinded independent investigator. Subjects were patients with primary or post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5), living

in Grenoble area, and willing to undergo a spa treatment course in La Lechere. The treated group had the three week spa treatment course in La Lechere, soon after randomization; the control group also had a spa treatment, but starting at day 365. The treatment consisted of four balncology sessions per day, six days a week during three weeks, and three educational workshops. An independent follow-tip was performed in Grenoble hospital every three months for 15 months. The main outcome criterion was the severity of the skin changes, as evaluated by means of malleolar chromametry. Quality of life, as measured by the Chronic Venous Insufficiency Questionnaire 2 scale, a visual analog scale (VAS) for leg symptoms, and the occurrence of leg ulcers were used as secondary criteria. The year after spa treatment in the treated group was compared with the year before spa treatment in the control group.

Results. Fifty-nine subjects were enrolled (29 in the treatment group and 30 in the control group). No statistically significant difference between groups was found at study onset regarding age, sex, etiology, CEAP “”C”" class, and the outcome variables.

Using pDCs derived from genetic knockout mice, we show that the myxoma virus-induced innate immune response requires the endosomal DNA sensor TLR9 and its adaptor MyD88, transcription factors IRF5 and IRF7, and the type I IFN positive-feedback loop mediated by IFNAR1. It is independent of the cytoplasmic RNA sensing pathway mediated by the mitochondrial adaptor molecule MAVS, the TLR3 adaptor TRIF, or the transcription factor IRF3. Using pharmacological

inhibitors, we demonstrate that myxoma virus-induced type I IFN and IL-12p70 production in murine pDCs is also dependent on phosphatidylinositol 3-kinase (PI3K) and Akt. Furthermore, our Epigenetics inhibitor results reveal that the N-terminal Z-DNA/RNA binding domain of vaccinia virulence factor E3, which is missing in the orthologous M029 protein expressed by myxoma virus, plays an inhibitory role in poxvirus sensing and innate cytokine production by murine pDCs.”
“Tuberculosis, which is caused by Mycobacterium tuberculosis, remains to be a global health problem. The thick and complex cell envelope has been implicated in many aspects of the pathogenicity of M. tuberculosis. CB-839 M. tuberculosis UDP-glucose pyrophosphorylase (UGP, coded by galU, Rv0993) is involved in cell

envelope precursor synthesis. UGP catalyzes the reversible formation of UDP-glucose and inorganic pyrophosphate from UTP and glucose 1-phosphate (Glc-1-P). Bacterial UGPs are completely unrelated to their eukaryotic counterparts. This enzyme is recognized as a virulence

factor in several bacterial species and is conserved among mycobacterial species, which makes it a good target for mycobacterial pathogenicity IKBKE research. The recombinant M. tuberculosis UGP (rMtUGP) was purified in Escherichia coli and found to be stable and catalytically active. The effects of pH, temperature and Mg2+ on enzyme activity were characterized. In addition, subcellular localization studies revealed that most of M. tuberculosis UGP protein was located in the cell wall. The purification and characterization of M. tuberculosis UGP may help to decipher the pathogenicity of M. tuberculosis. (C) 2008 Elsevier Inc. All rights reserved.”
“Nitrile and amide bioconversions have received attention through their ability to provide a range of commercially important chemicals. These bioconversions are mediated by distinct process strategies. Here, the processes performance is discussed, and the use of whole cells, cell extracts and enzymes as biocatalysts is compared. Additionally, the benefits of biocatalyst reuse through immobilization have been identified and immobilization matrices utilized for these bioconversions evaluated. Exploitation and commercial development will depend on optimization of the process performance and the capacity for scale-up in addition to the biocatalytic potential.

Contrast sensitivity was measured on 105 healthy patients with check details ages ranged from 19 to 26 years with visual acuity of 20/25 or better. The tests were performed in the same room and contrast sensitivity was measured with the VCTS-6500 system and CSV-1000. For both tests, the spatial frequencies

of 3, 6, 12 and 18 cycles per degree were recorded.

Contrast sensitivity values were generally higher for the Vistech VCTS-6500 test being the difference statistically significant (p < 0.001) for all the spatial frequencies. This difference was more significant for 3 cpd spatial frequency and the two tests showed a better agreement for the 6 cpd spatial frequency. Our results showed that there were significant differences between the VCTS-6500 and the CSV-1000 tests. Developments of some general recommendations or regulations in relation to clinical measurement of contrast sensitivity are necessary. (C) 2010 Elsevier Inc. All rights reserved.”
“Objective: The prognostic

relevance of subtypes within type B thymomas is controversial. The objective of this study was to evaluate the utility of World Health Organization (WHO) classification in patients with type B thymoma.

Methods: This was a retrospective review of 100 patients who underwent thymectomy for WHO type B thymoma. Recurrence patterns and survival were compared among subtypes.

Results: There were 22 type B1 tumors, 43 type B2 tumors, and 35 type B3 tumors. Incomplete resection occurred in 5 patients with type B1 thymoma, 8 with type B2 thymoma, and MK-2206 ic50 8 with type B3 thymoma (P = .87). Of the 79 patients with complete resection, tumor recurrence occurred in 1 (5.9%) patient with type B1 thymoma, 2 (5.7%) with type B2 thymoma, and 2 (7.4%) with type B3 thymoma, and all of these patients had Masaoka stage III disease. Disease-free survival at 5 years was 93%, 85%, and 82% in type

B1, B2, and B3, respectively (B1 vs B2; P = .79; B2 vs B3; P = 0.6). Disease-free survival at 5 years was 4-Aminobutyrate aminotransferase 94%, 100%, 61%, and 50% in Masaoka stages I, II, III, and IV, respectively (I vs II; P = .26; II vs III; P = .028; III vs IV; P = .002).

Conclusions: Tumor recurrence was significantly associated with advanced Masaoka stage regardless of the WHO subtype of type B thymomas. Given the heterogeneity of WHO type B thymomas, Masaoka stage should always be considered when predicting prognosis and planning adjuvant treatment for patients with type B thymomas. (J Thorac Cardiovasc Surg 2010;139:1431-5)”
“A 49-year-old woman developed a catatonic mute state a few weeks after methadone overdose. Clinical, radiological and histological findings were consistent with toxic spongiform leukoencephalopathy, which adds a potentially deadly side-effect to a generally considered safe substitution for heroin. (C) 2010 Elsevier Inc. All rights reserved.”
“Objective: Hypoxemia is a common problem of 1-lung ventilation.

2011.75; published online 25 April 2011″
“In the rabbit retina, there are two types of horizontal cell (HC). The axonless A-type HCs form a coupled network via connexin 50 (Cx50) gap junctions in the outer plexiform layer (OPL). The axon-bearing B-type HCs form two independently coupled networks; the dendritic network via gap junctions consisted of unknown Cx and the axon terminal network via Cx57. The present study was conducted to examine the localization selleck screening library and morphological features of Cx50 and Cx57

gap junctions in rabbit HCs at cellular and subcellular levels. The results showed that each gap junction composed of Cx50 or Cx57 showed distinct features. The larger Cx50 gap junctions were located more proximally than the smaller Cx50 gap junctions. Both Cx50 plaques formed symmetrical homotypic gap junctions, but some small ones had an asymmetrical appearance, suggesting the presence of heterotypic gap junctions

or hemichannels. In contrast, Cx57 gap junctions were found in the more distal part of the OPL but never on the axon terminal endings entering the rod spherules, and they were exclusively homotypic. Interestingly, about half of the Cx57 gap junctions appeared to be invaginated. These distinct features of Cx50 and Cx57 gap junctions show the variety of HC gap selleck junctions and may provide insights into the function of different types of HCs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“The AP-1 transcription factor is a dimeric protein complex formed primarily between Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra-1, Fra-2) family members. These distinct AP-1 complexes are expressed in many cell types and modulate target gene expression implicated in cell proliferation, differentiation, and stress responses. Although the importance of AP-1 has long been recognized, the biochemical characterization of AP-1 remains limited PIK3C2G in part due to the difficulty in purifying full-length, reconstituted dimers with active DNA-binding and transcriptional activity. Using a combination of bacterial coexpression and epitope-tagging methods, we successfully purified all 12 heterodimers

(3 Jun x 4 Fos) of full-length human AP-1 complexes as well as c-Jun/c-Jun, JunD/JunD, and c-Jun/JunD dimers from bacterial inclusion bodies using one-step nickel-NTA affinity tag purification following denaturation and renaturation of coexpressed AP-1 subunits. Coexpression of two constitutive components in a dimeric AP-1 complex helps stabilize the proteins when compared with individual protein expression in bacteria. Purified dimeric AP-1 complexes are functional in sequence-specific DNA binding, as illustrated by electrophoretic mobility shift assays and DNase I footprinting, and are also active in transcription with in vitro-reconstituted human papillomavirus (HPV) chromatin containing AP-1-binding sites in the native configuration of HPV nucleosomes.

As with any other procedure, patient selection and lesion selection are important factors in determining outcome.”
“The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT1A receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission 17-AAG ic50 tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [C-11]WAY10035 (n=13)

and [C-11]MADAM (n=8) to study 5-HT1A and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E-2), progesterone

(P-4), follicle stimulating hormone (FSH) and luteinizing hormone (LH). The 5-HT1A receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E-2 or P-4 values with the change in 5-HT1A receptor or 5-HTT BPs. The results provide principally a new in vivo finding in Angiogenesis inhibitor human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT1A receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences

in serotonin-associated disorders. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Expression levels of buy 5-FU the same mRNA or protein vary significantly among the cells of an otherwise identical population. Such biological noise has great functional implications and is largely due to transcriptional bursting, the episodic production of mRNAs in short, intense bursts, interspersed by periods of transcriptional inactivity. Bursting has been demonstrated in a wide range of pro- and eukaryotic species, attesting to its universal importance. However, the mechanistic origins of bursting remain elusive. A different type of phenomenon, which has also been suggested to be widespread, is the physical interaction between the promoter and 3′ end of a gene. Several functional roles have been proposed for such gene loops, including the facilitation of transcriptional reinitiation. Here, I discuss the most recent findings related to these subjects and argue that gene loops are a likely cause of transcriptional bursting and, thus, biological noise.”
“The lack of apoptotic pathways may lead to undesirable cell survival and proliferation, which are recognized hallmarks of cancer. It is well known that exposure to cigarette smoke induces DNA lesions in pulmonary cells. At present, it is not fully elucidated whether these lesions are repaired to restore normal functions or induce apoptosis.