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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 19 recordsLinked to original sources

Function of cardiac M3 receptors.

1. Since the initial identification of the M3 subtype of muscarinic acetylcholine receptors (M3-mAChR) in the heart, there have been increasing interest and advances in studies on the pathophysiological roles of M3-mAChR in the heart. Recent studies from several laboratories have provided compelling and solid evidence in support of the important roles of M3-mAChR in regulation and maintenance of cardiac function and in generation and progression of heart disease as well. 2. The functions of the cardiac M3-mAChR revealed thus far include (i) M3-mAChR regulation of heart rate and cardiac repolarization, (ii) modulation of inotropic effects, (iii) cytoprotection against ischaemic injuries of myocardium, (iv) regulation of cell-to-cell communication, and (v) participation in generation and maintenance of atrial fibrillation. 3. Signal transduction mechanisms underlying these pathophysiological functions have also been studied, which have allowed us to get insight into the following mechanistic aspects. (i) M3-mAChR activates a delayed rectifying K+ current I(KM3) to participate in cardiac repolarization, negative chronotropic actions, and anti-dysrhythmic (suppresses ischaemic dysrhythmias) as well as pro-dysrhythmic (facilitates atrial fibrillation) actions. (ii) M3-mAChR interacts with gap-junctional channel connexin 43 to maintain cell-cell communication and excitation propagation. (iii) M3-mAChR regulates intracellular phosphoinositide hydrolysis to improve cardiac contraction and haemodynamic function. (iv) M3-mAChR activate anti-apoptotic signalling molecules, enhances endogenous antioxidant capacity, and diminishes intracellular Ca2+ overload, all of which contribute to protecting the heart against ischaemic injuries. 4. This article provides an overview of the potential roles of the M3-mAChR in parasympathetic control of heart function under normal physiological conditions and in the setting of a variety of pathological processes including heart failure, myocardial ischaemia and dysrhythmias.

Animals↗

Nanometer-scale ablation with a table-top soft x-ray laser.

Ablation of holes with diameters as small as 82 nm and very clean walls was obtained in poly(methyl methacrylate) focusing pulses from a Ne-like Ar 46.9 nm compact capillary-discharge laser with a freestanding Fresnel zone plate diffracting into third order. These results demonstrate the feasibility of using focused soft x-ray laser beams for the direct nanoscale patterning of materials and the development of new nanoprobes.

Journal Article↗

Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid.

The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment.

Animals↗

Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation in response to endurance training.

OBJECTIVE: The crucial role of haemoglobin in endurance performance has been well documented. We examined whether polymorphisms in the HBB gene modified aerobic capacity. METHODS: 102 recruits were trained by running 5000 m three times per week for 18 weeks. Exercise intensity progressively increased from an initial heart rate corresponding to 95% of the individual baseline ventilatory threshold during the first 10 weeks to 105% during the last 8 weeks. The phenotypes measured were running economy and VO(2)max. Running economy was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1) and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the -551C/T, intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site variants by PCR-RFLP. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium at three loci. None of the running economy and VO(2)max-related traits were associated with the three polymorphisms or haplotypes at baseline, while the training response of running economy was associated with -551C/T and intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C had decreased oxygen cost of running compared to the other individuals. DISCUSSION: It was concluded that the -551C/C or intron2,+16C/C genotype might explain part of the individual variation in the cardiorespiratory adaptation to endurance training.

Adaptation, Physiological↗

Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway.

Taurine is found in bone tissue, but its function in skeletal tissue is not fully understood. The present study was undertaken to investigate regulation of gene expression of connective tissue growth factor (CTGF), and the roles of mitogen-activated protein kinases (MAPKs) in murine osteoblast MC3T3-E1 cells treated with taurine. Western blot analysis showed taurine stimulated CTGF protein secretion in a dose- and time-dependent manner. Taurine induced activation of extracellular signal-regulated kinase (ERK), but not p38 and c-jun N-terminal Kinase (JNK), in osteoblasts. Furthermore, pretreatment of osteoblasts with the ERK inhibitor PD98059 abolished the taurine-induced CTGF production. These data indicate that taurine induces CTGF secretion in MC3T3-E1 cells mediated by the ERK pathway, and suggest that osteoblasts are direct targets of taurine.

Animals↗

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

Action Potentials↗

Comparison of mechanical debridement and radiofrequency energy for chondroplasty in an in vivo equine model of partial thickness cartilage injury.

OBJECTIVE: The purpose of this study was to develop a long-term model of cartilage injury that could be used to compare the effects of radiofrequency energy (RFE) and mechanical debridement as a treatment. METHODS: Partial thickness fibrillation of patellar cartilage was created in 16 mature ponies. Three months after the initial surgery all injured patellae were randomly selected to receive one of the four treatments (n = 8/treatment): (1) control, (2) mechanical debridement with a motorized shaver, (3) TAC-CII RFE probe, and (4) CoVac 50 RFE probe. The ponies were euthanized 22 months after treatment. Macroscopic appearance of the cartilage surface was scored, vital cell staining was used to determine chondrocyte viability and light microscopy was used to grade the morphometric changes within the cartilage. Mechanical properties (aggregate modulus, Poisson's ratio and permeability) also were determined and compared to normal uninjured cartilage. RESULTS: There were no differences in the cartilage surface scores among the treatment groups and control samples (P > 0.05). The maximum depth of cell death and the percentage of dead area in control and mechanical debridement groups were significantly less than those in both RFE groups. There were no significant differences in maximum depth and the percentage of dead area between the two RFE treatment groups. Histologic scores demonstrated better cartilage morphology for the control and mechanical debridement groups than those of RFE groups. However, even with full thickness chondrocyte death, the matrix in the RFE treated sections was still retained and the mechanical properties of the treated cartilage did not differ from the mechanical debridement group. CONCLUSION: RFE caused greater chondrocyte death and more severe morphological changes compared to untreated degenerative cartilage and mechanical debridement in this model.

Animals↗

Choroid plexus cysts do not affect fetal neurodevelopment.

OBJECTIVE: To determine whether an isolated finding of a choroid plexus cyst (CPC) during routine ultrasound is associated with altered fetal growth or development. STUDY DESIGN: Prospective, case-control study comparing 35 CPC cases to 67 controls. Neurobehavioral development assessment included 50 min long serial recordings of heart rate, motor activity and their interrelation at 24, 28, 32 and 36 weeks gestation. Growth measurement was based on three ultrasound evaluations of femur length, biparietal diameter, head circumference and abdominal circumference at initial exam, 28 and 36 weeks. RESULTS: Longitudinal analyses revealed no differences in fetal heart rate, variability or accelerations; the number or duration of fetal movements or total motor activity; nor fetal movement-fetal heart rate coupling. CPC cases had slightly smaller head and abdominal circumferences at 28 weeks, but these differences had disappeared by 36 weeks. CPC detection was more common when routine exams were conducted earlier (18.8 versus 19.5 weeks; P<0.01). CONCLUSION: Despite the presumption that CPCs with normal karyotypes are benign variants, little empirical support exists. These results indicate that CPCs detected by prenatal ultrasound do not pose or reveal a threat to fetal development.

Adult↗

Proximal femoral density and geometry measurements by quantitative computed tomography: association with hip fracture.

INTRODUCTION: Bone mineral density and geometry measurements by volumetric quantitative computed tomography (vQCT) have been utilized in clinical research studies of aging, pharmacologic intervention and mechanical unloading, but there is relatively little information about the association of these measures with hip fracture. To address this issue, we have carried out a study comparing vQCT parameters in elderly Chinese women with hip fractures with measurements in age-matched controls. MATERIALS AND METHODS: Forty-five women (mean age 74.71+/-5.94) with hip fractures were compared to 66 age-matched control subjects (mean age 70.70+/-4.66). vQCT was employed to characterize the volumetric bone mineral density in cortical, trabecular, and integral volumes of interest in the proximal femur. In addition to the volume of interest measurements, we computed the cross-sectional areas of the femoral neck and intertrochanteric planes, the femoral neck axis length, indices of femoral neck bending and compressive strength, and measures of femoral neck cortical geometry. To determine if cortical geometry measures were associated with hip fracture independently of trabecular vBMD, we carried out multi-variate analyses including these parameters in a logistic regression model. RESULTS AND CONCLUSIONS: All vQCT measurements discriminated between fractured subjects and age-matched controls. There was no significant difference in predictive strength between volumetric and areal representations of BMD and trabecular and integral vBMD showed comparable discriminatory power, although both of these measures were more correlated to fracture status than cortical vBMD. We found that fractured subjects had larger femoral neck cross-sectional areas, consistent with adaptation to lower BMD in these osteoporotic subjects. The larger neck cross-sectional areas resulted in bending strength indices in the fractured subjects that were comparable or larger than those of the control subjects. In multi-variate analyses, reduced femoral neck cortical thickness and buckling ratio indices were associated with fracture status independently of trabecular vBMD.

Aged↗

Comparison of BMD precision for Prodigy and Delphi spine and femur scans.

INTRODUCTION: Precision error in bone mineral density (BMD) measurement can be affected by patient positioning, variations in scan analysis, automation of software, and both short- and long-term fluctuations of the densitometry equipment. Minimization and characterization of these errors is essential for reliable assessment of BMD change over time. METHODS: We compared the short-term precision error of two dual-energy X-ray absorptiometry (DXA) devices: the Lunar Prodigy (GE Healthcare) and the Delphi (Hologic). Both are fan-beam DXA devices predominantly used to measure BMD of the spine and proximal femur. In this study, 87 women (mean age 61.6+/-8.9 years) were measured in duplicate, with repositioning, on both systems, at one of three clinical centers. The technologists were International Society for Clinical Densitometry (ISCD) certified and followed manufacturer-recommended procedures. All scans were acquired using 30-s scan modes. Precision error was calculated as the root-mean-square standard deviation (RMS-SD) and coefficient of variation (RMS-%CV) for the repeated measurements. Right and left femora were evaluated individually and as a combined dual femur precision. Precision error of Prodigy and Delphi measurements at each measurement region was compared using an F test to determine significance of any observed differences. RESULTS: While precision errors for both systems were low, Prodigy precision errors were significantly lower than Delphi at L1-L4 spine (1.0% vs 1.2%), total femur (0.9% vs 1.3%), femoral neck (1.5% vs 1.9%), and dual total femur (0.6% vs 0.9%). Dual femur modes decreased precision errors by approximately 25% compared with single femur results. CONCLUSIONS: This study suggests that short-term BMD precision errors are skeletal-site and manufacturer specific. In clinical practice, precision should be considered when determining: (a) the minimum time interval between baseline and follow-up scans and (b) whether a statistically significant change in the patient's BMD has occurred.

Absorptiometry, Photon↗

Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells.

Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA:SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.

Animals↗

Quality and performance measures in bone densitometry. Part 2: fracture risk.

INTRODUCTION: This is part 2 of a core chapter of the forthcoming Report on Bone Densitometry commissioned by the International Commission on Radiation Units (ICRU). It is written with the aim to review definitions of quantities and units used in bone densitometry research and to describe parameters and methods that can be used to compare and standardize densitometric equipment and measurements. Part 2 of this chapter contains the section on fracture risk. PERFORMANCE MEASURES IN THE ASSESSMENT OF FRACTURE RISK: Building on concepts of risk assessment, including risk ratios and odds ratios, we review statistical concepts commonly used in cross-sectional and prospective fracture studies. Performance measures are defined that allow a comparison of the ability of densitometry techniques to assess fracture risk. DISCUSSION: The methods of discriminant analysis, logistic regression, Poisson regression models, and the Cox proportional hazard model are presented and compared. In addition, statistical concepts to characterize risk for the individual patient are reviewed.

Aged↗

Effects of osmotic pressure in the extracellular matrix on tissue deformation.

In soft tissues, large molecules such as proteoglycans trapped in the extracellular matrix (ECM) generate high levels of osmotic pressure to counter-balance external pressures. The semi-permeable matrix and fixed negative charges on these molecules serve to promote the swelling of tissues when there is an imbalance of molecular concentrations. Structural molecules, such as collagen fibres, form a network of stretch-resistant matrix, which prevents tissue from over-swelling and keeps tissue integrity. However, collagen makes little contribution to load bearing; the osmotic pressure in the ECM is the main contributor balancing external pressures. Although there have been a number of studies on tissue deformation, there is no rigorous analysis focusing on the contribution of the osmotic pressure in the ECM on the viscoelastic behaviour of soft tissues. Furthermore, most previous works were carried out based on the assumption of infinitesimal deformation, whereas tissue deformation is finite under physiological conditions. In the current study, a simplified mathematical model is proposed. Analytic solutions for solute distribution in the ECM and the free-moving boundary were derived by solving integro-differential equations under constant and dynamic loading conditions. Osmotic pressure in the ECM is found to contribute significantly to the viscoelastic characteristics of soft tissues during their deformation.

Animals↗

Oncolytic adenovirus-mediated transfer of the antisense chk2 selectively inhibits tumor growth in vitro and in vivo.

Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such therapeutics remains a major challenge. To resolve this problem, we constructed M3, a novel recombinant adenovirus with a 27-bp deletion in E1A CR2 region by which to realize tumor-specific replication, and an 829-bp of antisense chk2 fragment inserted into the E3 coding region. In this design, M3 exploited the native adenovirus E3 promoters to express antisense chk2 cDNA in a viral replication-dependent fashion, and preferentially silenced the chk2 gene in tumor cells. In vitro and in vivo assays confirmed that downregulated chk2 expression induced by M3 infection was tumor-specific and virus replication-dependent. Furthermore, systemic administration of M3 combined with a low dose of cisplatin cured 75% (9/12) of orthotopic hepatic carcinoma mouse models that were otherwise resistant to cisplatin. Our results indicated that the upcoming development in this field would improve the antitumor efficacy and maximize the synergistic effect of oncolytic viruses administered with traditional chemotherapy or radiotherapy.

Adenoviridae↗

Taurine transporter is expressed in osteoblasts.

Taurine influences bone metabolism and is taken up by cells via a specific transport system, the taurine transporter (TAUT). We report a link between taurine and bone homeostasis by demonstrating transcription and translation of TAUT in bone-forming cells. TAUT was expressed in human primary osteoblasts, the human osteosarcoma osteoblast-like cell line MG63, and the mouse osteoblastic cell line MC3T3-E1. Immunostaining with polyclonal antibodies also demonstrated the presence of TAUT in both human and murine osteoblasts. TAUT mRNA expression and [(3)H]taurine uptake increased during differentiation of MG63 cells in culture. Supplementation of culture medium with taurine enhanced alkaline phosphatase activity and osteocalcin secretion. The regulation and detailed function of taurine and TAUT in bone remain unclear, but our findings suggest a functional role for them in bone homeostasis.

3T3 Cells↗

Young-elderly differences in bone density, geometry and strength indices depend on proximal femur sub-region: a cross sectional study in Caucasian-American women.

Fragility fractures at the trochanter (TR) and the femoral neck (FN) have distinct etiologies, but the underlying age-related structural changes at these proximal femoral sub-regions are poorly understood. 28 young (41+/-3 years) and 124 elderly (74+/-3 years) healthy Caucasian women underwent volumetric quantitative computed tomography at the hip. Integral (i), cortical (c) and trabecular (t) bone mineral density and content (BMD, BMC) were measured. Geometric parameters included cross sectional area (CSA), and volumes of the integral, cortical and trabecular regions (VOL). Structural measures included indices of compressive (Compstr) and bending (BSI) strength. After adjusting for height and weight, an F-test was used to compare the TR and the FN mean values between young and elderly and to test for interaction to compare logarithmic difference of young and elderly (log(Young)-log(Elderly), Y/Ed) between the FN and the TR in an ANOCOVA model. All BMC, iBMD and tBMD values were significantly lower in elderly than in young women, with the largest Y/Ed in the FN tBMC and tBMD (P<0.0011 and P<0.0001). cBMD in young and elderly groups was not significantly different at the TR while at the FN it was greater (P=0.0075) in elderly than young women, showing significant Y/Ed (P=0.0003) dependence on skeletal site. Elderly women had significantly larger iVOL and CSA values (0.0001<P<0.0051), except for the FN iVOL. cVOL values were smaller in elderly than young women (P<0.0001). Y/Ed in bone geometry differed by sub-region only for cVOL measures (P=0.0267). Despite larger CSA and iVOL measures in elderly, the younger women had greater Compstr (P<0.0001) and BSI (P=0.0051). Thus, although both the TR and the FN appear to increase in size with age, this enlargement is insufficient to protect against loss of bone strength.

Adult↗

Enhancement of antitumor activity of the anti-EGF receptor monoclonal antibody cetuximab/C225 by perifosine in PTEN-deficient cancer cells.

Mutational inactivation or deletion of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/MMAC1/TEP gene in human cancer cells leads to a constitutively active status of the phosphatidylinositol 3-kinase/Akt pathway in the cells and has been linked to the lack of responses of the cells to the epidermal growth factor (EGF) receptor-targeted therapeutics. Akt is strongly inhibited by perifosine, an orally active alkyl-lysophospholipid currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials. To determine whether perifosine may enhance the antitumor activity of the anti-EGF receptor monoclonal antibody cetuximab/C225 in PTEN-deficient cancer cells, we exposed MDA468 breast cancer cells (which contain mutated PTEN gene) and PC3 prostate cancer cells (in which the PTEN gene is deleted) to perifosine and cetuximab, alone and in combination. Treatment of the cells with perifosine reduced baseline levels of phosphorylated Akt, phosphorylated p44/42 mitogen-activated protein kinase (MAPK) and p38MAPK, and increased baseline levels of phosphorylated stress-activated protein kinase (SAPK)/c-jun NH(2)-terminal kinase (JNK). A 72-h exposure of the MDA468 and PC3 cells to perifosine alone resulted in cell death in a dose-dependent manner, which was enhanced by cetuximab. Addition of subtoxic doses of perifosine to cetuximab treatment also enhanced the cetuximab-induced growth inhibition. The combination treatment enhanced the inhibition of phosphorylation of Akt, p44/42MAPK and p38MAPK, but offset the phosphorylation of SAPK/JNK that was activated by perifosine treatment alone. Taken together, the data showed that perifosine enhances the antitumor activity of cetuximab in PTEN-deficient cancer cells. Further evaluation of the combination treatment in preclinical and clinical studies is warranted.

Antibodies, Monoclonal↗

Gain of 1q25-32, 12q23-24.3, and 17q12-22 facilitates tumorigenesis and progression of human squamous cell lung cancer.

To explore the genetic changes involved in the stepwise development of lung cancer, we have determined the genetic events associated with the histological progression from normal bronchial epithelium to squamous cell carcinoma. Comparative genomic hybridization was used to identify chromosomal imbalances in 54 microdissected samples, including squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumour derived from 23 patients with squamous cell carcinoma of the lung. Histopathological progression was accompanied by an increased number of chromosomal abnormalities. Gains of 1q25-32, 12q23-24.3, and 17q12-22, in particular, were detected at high frequencies in both carcinoma in situ and invasive tumours and were found more often in the cases with lymph node metastases than in those without. Our previous expression profiling of squamous cell carcinomas had identified overexpression of laminin5 gamma2, a gene located at 1q25-31. Therefore, this was investigated at the protein level by immunohistochemical analysis in 336 samples of squamous cell carcinoma of the lung. Consistent with the genomic data for this region, the expression level of laminin5 gamma2 was higher in the primary tumours with lymph node metastases than in tumours without metastases (p = 0.012). These data suggest that gains of genes from 1q25-32, 12q23-24.3, and 17q12-22 facilitate tumorigenesis and progression of squamous cell carcinoma of the lung, and may serve as potential predictors for this disease.

Aged↗