The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known.</p> <p>Methods</p> <p>We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC).</p> <p>Results</p> <p>The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, <it>P </it>= 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, <it>P </it>< 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, <it>P </it>< 0.001), progesterone receptor positive (71.1% vs. 50.1%, <it>P </it>< 0.001) and HER2 negative (97.5% vs. 74.6%, <it>P </it>< 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, <it>P </it>< 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, <it>P </it>< 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, <it>P </it>= 0.57; HR 0.75 for death, 95% CI 0.18-3.09, <it>P </it>= 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, <it>P </it>= 0.001; HR 1.50 for death, 95% CI 0.97-2.33, <it>P </it>= 0.07).</p> <p>Conclusions</p> <p>ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.</p

Impairment of Nuclear Factor-κB Activation Increased Glutamate Excitotoxicity in a Motoneuron-Neuroblastoma Hybrid Cell Line Expressing Mutant (G93A) Cu/Zn-Superoxide Dismutase

Mutations in the superoxide dismutase 1 (SOD1) gene are linked to glutamate excitotoxicity in familial amyotrophic lateral sclerosis (fALS), but the underlying mechanism remains unclear. We investigated whether nuclear factor-kappa B (NE-kappa B) activation is involved in glutamate excitotoxicity by using motor neuron neuroblastoma hybrid cells that expressed a mutant (G93A) SOD1 (mtSOD1) or wild-type SOD1 (wtSOD1). MtSOD1 cells were more vulnerable to glutamate excitotoxicity than wtSOD1 cells and showed higher NE-kappa B activity, higher nuclear cRel expression, and lower nuclear RelA expression under basal conditions. Glutamate treatment increased NF-kappa B activation along with nuclear expressions of RelA and cRel in wtSOD1 cells but induced only weak nuclear RelA expression in mtSOD1 cells. Suppression of NF-kappa B activation using transfection of the superrepressive mutant form of l kappa B alpha (Ml kappa B alpha) inhibited nuclear RelA expression in both types of SOD1 cells, which increased glutamate excitotoxicity in wtSOD1 cells but not in mtS0D1 cells. Furthermore, immunohistochemistry confirmed stronger RelA immunoreactivity in the nuclei of motor neurons of spinal cord in wild-type SOD1 transgenic mice than in those in SOD1 G93A transgenic mice. In addition, we found that glutamate treatment decreased XIAP expression and increased caspase-3 activity in mtSOD1 cells and mIKBet-overexpressing wtSOD1 cells. Our results suggest that glutamate excitotoxicity in motor neurons of SOD1-linked fALS is attributable, at least in part, to the impairment of l kappa B alpha-dependent RelA activation and subsequent apoptosis mediated by XIAP inhibition and caspase-3 activation.Fan W, 2009, INVEST OPHTH VIS SCI, V50, P917, DOI 10.1167/iovs.08-2555Lee CH, 2007, BIOFACTORS, V29, P19Memet S, 2006, BIOCHEM PHARMACOL, V72, P1180, DOI 10.1016/j.bcp.2006.09.003Pizzi M, 2006, EUR J PHARMACOL, V545, P22, DOI 10.1016/j.ejphar.2006.06.027Harris J, 2006, J IMMUNOL, V177, P2527Tergaonkar V, 2006, INT J BIOCHEM CELL B, V38, P1647, DOI 10.1016/j.biocel.2006.03.023Ishige K, 2005, NEUROCHEM INT, V47, P545, DOI 10.1016/j.neuint.2005.07.010Pizzi M, 2005, CELL DEATH DIFFER, V12, P761, DOI 10.1038/sj.cdd.4401598Ralph GS, 2005, NAT MED, V11, P429, DOI 10.1038/nm1205Jiang YM, 2005, ANN NEUROL, V57, P236, DOI 10.1002/ana.20379Huang Y, 2005, NEUROSCI LETT, V373, P115, DOI 10.1016/j.neulet.2004.09.074Viatour P, 2005, TRENDS BIOCHEM SCI, V30, P43, DOI 10.1016/j.tiba.2004.11.009Kunst CB, 2004, AM J HUM GENET, V75, P933Bonizzi G, 2004, TRENDS IMMUNOL, V25, P280, DOI 10.1016/j.it.2004.03.008Nam SY, 2003, CANCER SCI, V94, P1066Miller RG, 2003, AMYOTROPH LATERAL SC, V4, P191Chen XF, 2003, CANCER RES, V63, P1059Dunlop J, 2003, J NEUROSCI, V23, P1688Casciati A, 2002, J NEUROCHEM, V83, P1019Lee KW, 2002, INT J DEV NEUROSCI, V20, P521Pizzi M, 2002, J BIOL CHEM, V277, P20717, DOI 10.1074/jbc.M201014200Salvesen GS, 2002, NAT REV MOL CELL BIO, V3, P401, DOI 10.1038/nrm830Flanagan SW, 2002, J NEUROCHEM, V81, P170Howland DS, 2002, P NATL ACAD SCI USA, V99, P1604Gelinas DF, 2000, AMYOTROPH LATERAL SC, V1, P3Karin M, 2000, ANNU REV IMMUNOL, V18, P621Gilmore TD, 1999, ONCOGENE, V18, P6842Tamatani M, 1999, J BIOL CHEM, V274, P8531Wang XT, 1997, ONCOGENE, V15, P2991Mattson MP, 1997, J NEUROSCI RES, V49, P681Hunot S, 1997, P NATL ACAD SCI USA, V94, P7531Gurney ME, 1997, J NEUROL, V244, pS15Gurney ME, 1996, ANN NEUROL, V39, P147KIM WH, 1994, CANCER RES, V54, P5005GURNEY ME, 1994, SCIENCE, V264, P1772

Tuberculosis infection and lung adenocarcinoma:Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.</p