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Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR 9 (Toll-Like Receptor 9)-Mediated Atherosclerosis

Li, Jieliang; Huynh, Luong; Cornwell, William D; Tang, Moon-Shong; Simborio, Hannah; Huang, Jing; Kosmider, Beata; Rogers, Thomas J; Zhao, Huanqing; Steinberg, Michael B; Thu Thi Le, Le; Zhang, Lanjing; Pham, Kien; Liu, Chen; Wang, He
OBJECTIVE:classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. CONCLUSIONS:E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.
PMID: 33380174
ISSN: 1524-4636
CID: 4785712

E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1

Pham, Kien; Huynh, Do; Le, Le; Delitto, Daniel; Yang, Lei; Huang, Jing; Kang, Yibin; Steinberg, Michael B; Li, Jieliang; Zhang, Lanjing; Liu, Dongfang; Tang, Moon-Shong; Liu, Chen; Wang, He
Young women represent a target of E-cigarette (E-cig) companies, raising concern for potential connections with breast cancer (BC) that have not yet been elucidated. We hypothesized that E-cig promotes BC development and lung metastasis possibly through BC-monocyte/tumor-associated macrophage (TAM) crosstalk via CCL5 and V-CAM-1 axes. We demonstrated that E-cig promoted the infiltration of circulating monocytes in mammary fat pad (MFP) model. Furthermore, E-cig exposure significantly enhanced BC cell growth in MFP tumor and metastatic lung colonization; immunohistochemical stains illustrated the increase of TAMs infiltration, reduced BC cell apoptosis and increased proliferation index after E-cig exposure. In vitro studies show E-cig vapor condensate (EVC) treatment upregulated protein expressions of CCL5, V-CAM-1, and other pro-tumorigenic factors in BC cells. Mechanistically, co-culture system demonstrated both EVC and macrophages independently stimulated BC cell growth and the migration via CCL5/CCR1/CCR5 axis. During metastasis, E-Cig exposure stimulated BC cell survival via direct interaction with infiltrated macrophages, regulated by VCAM-1 and integrin α4β1. Our findings, for the first time, showed that E-cig promotes BC growth and metastasis. This study highlights the critical role of TAMs via CCL5 and VCAM-1 pathways in E-cig promoted BC tumor development.
PMID: 32829009
ISSN: 1872-7980
CID: 4586762

Problems in the reproducibility of classification of small lung adenocarcinoma: an international interobserver study

Shih, Angela R; Uruga, Hironori; Bozkurtlar, Emine; Chung, Jin-Haeng; Hariri, Lida P; Minami, Yuko; Wang, He; Yoshizawa, Akihiko; Muzikansky, Alona; Moreira, Andre L; Mino-Kenudson, Mari
AIMS/OBJECTIVE:The 2015 WHO classification for lung adenocarcinoma (ACA) provides criteria for adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (INV), but differentiating these entities can be difficult. As our understanding of prognostic significance increases, inconsistent classification is problematic. This study assesses agreement within an international panel of lung pathologists and identifies factors contributing to inconsistent classification. METHODS AND RESULTS/RESULTS:Sixty slides of small lung ACAs were reviewed digitally by six lung pathologists in three rounds, with consensus conferences and examination of elastic stains in round 3. The panel independently reviewed each case to assess final diagnosis, invasive component size and predominant pattern. The kappa value for AIS and MIA versus INV decreased from 0.44 (round 1) to 0.30 and 0.34 (rounds 2 and 3). Interobserver agreement for invasion (AIS versus other) decreased from 0.34 (round 1) to 0.29 and 0.29 (rounds 2 and 3). The range of the measured invasive component in a single case was up to 19.2 mm among observers. Agreement was excellent in tumours with high-grade cytology and fair with low-grade cytology. CONCLUSIONS:Interobserver agreement in small lung ACAs was fair to moderate, and improved minimally with elastic stains. Poor agreement is primarily attributable to subjectivity in pattern recognition, but high-grade cytology increases agreement. More reliable methods to differentiate histological patterns may be necessary, including refinement of the definitions as well as recognition of other features (such as high-grade cytology) as a formal part of routine assessment.
PMID: 31107973
ISSN: 1365-2559
CID: 4100592

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study

Maleki, Zahra; Baloch, Zubair; Lu, Ryan; Shafique, Khurram; Song, Sharon J; Viswanathan, Kartik; Rao, Rema A; Lefler, Holly; Fatima, Aisha; Wiles, Austin; Jo, Vickie Y; Wang, He; Fadda, Guido; Powers, Celeste N; Ali, Syed Z; Pantanowitz, Liron; Siddiqui, Momin T; Nayar, Ritu; Klijanienko, Jerzy; Barkan, Guliz A; Krane, Jeffrey F; Rossi, Esther D; Callegari, Fabiano; Kholová, Ivana; Bongiovanni, Massimo; Faquin, William C; Pusztaszeri, Marc P
BACKGROUND:The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs. METHODS:Submandibular gland FNA cytology specimens from 15 international institutions (2013-2017) were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. A correlation with the available histopathologic follow-up was performed, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS:The case cohort of 734 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 21.4% (0%-50%); nonneoplastic, 24.2% (9.1%-53.6%); AUS, 6.7% (0%-14.3%); benign neoplasm, 18.3% (0%-52.5%); SUMP, 12% (0%-37.7%); SM, 3.5% (0%-12.5%); and malignant, 13.9% (2%-31.3%). The histopathologic follow-up was available for 333 cases (45.4%). The ROMs were as follows: nondiagnostic, 10.6%; nonneoplastic, 7.5%; AUS, 27.6%; benign neoplasm, 3.2%; SUMP, 41.9%; SM, 82.3%; and malignant, 93.6%. CONCLUSIONS:This multi-institutional study shows that the ROM of each MSRSGC category for submandibular gland FNA is similar to that reported for parotid gland FNA, although the reported rates for the different MSRSGC categories were variable across institutions. Thus, the MSRSGC can be reliably applied to submandibular gland FNA.
PMID: 31050186
ISSN: 1934-6638
CID: 3908822

Barrett's esophagus: endoscopic diagnosis

Ishimura, Norihisa; Amano, Yuji; Appelman, Henry D; Penagini, Roberto; Tenca, Andrea; Falk, Gary W; Wong, Roy K H; Gerson, Lauren B; Ramirez, Francisco C; Horwhat, J David; Lightdale, Charles J; DeVault, Kenneth R; Freschi, Giancarlo; Taddei, Antonio; Bechi, Paolo; Ringressi, Maria Novella; Castiglione, Francesca; Degl'Innocenti, Duccio Rossi; Wang, Helen H; Huang, Qin; Bellizzi, Andrew M; Lisovsky, Mikhail; Srivastava, Amitabh; Riddell, Robert H; Johnson, Lawrence F; Saunders, Michael D; Chuttani, Ram
This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes
PMID: 21950807
ISSN: 1749-6632
CID: 139917

Hyalinizing trabecular adenoma--an uncommon thyroid tumor frequently misdiagnosed as papillary or medullary thyroid carcinoma

Evenson, Amy; Mowschenson, Peter; Wang, Helen; Connolly, James; Mendrinos, Savvas; Parangi, Sareh; Hasselgren, Per-Olof
BACKGROUND: Hyalinizing trabecular adenoma (HTA) is an uncommon benign thyroid tumor that can present as a solitary thyroid nodule, a prominent nodule in a multinodular goiter, or as an incidental finding in a thyroidectomy specimen. The clinical significance of the lesion is that it is frequently misdiagnosed as papillary carcinoma on fine-needle aspiration cytology or as papillary or medullary carcinoma on histopathological section. We reviewed our recent experience with 7 patients diagnosed with HTA. METHODS: Fine-needle aspiration biopsy was performed in 7 patients presenting with a solitary thyroid nodule (n = 4) or a multinodular goiter (n = 3). The patients underwent total thyroidectomy (n = 6) or hemithyroidectomy (n = 1). RESULTS: In 4 patients, the preoperative cytology was suggestive of papillary carcinoma, in 2 patients suspicious, and in 1 patient positive for papillary carcinoma. On histopathological section, 2 patients had a microscopic HTA, 2 patients had HTA in 1 or 2 nodules of a multinodular goiter, and 3 patients had HTA in a solitary nodule. Except in 1 patient, who had a microscopic focus (3.2 mm) of papillary carcinoma, there was no evidence of malignancy in the surgical specimens on permanent histopathological section. CONCLUSIONS: Although HTA is a rare condition of the thyroid, the surgeon needs to be aware of this entity to be able to better discuss the pathological findings with the patient, particularly since some pathologists and endocrinologists believe that HTA may represent a malignant neoplasm of low metastatic potential
PMID: 17512281
ISSN: 1879-1883
CID: 105599

Liposomal delivery systems: In vitro evaluation to predict in vivo analgesic efficacy in a mouse model [Meeting Abstract]

Bolotin, EM; Piskoun, B; Wang, H; Bansinath, M; Turndorf, H; Grant, GJ
ISSN: 0003-2999
CID: 53564