Immunofluorescent co-staining of CHI3L1 and F4/80 in the lung of CCSP-rtTA/(TetO)₇-CMV-Stat3C mice.

<p>CCSP-rtTA/(TetO)₇-CMV-Stat3C bitransgenic mice were treated (+DOX) or untreated (-DOX) with doxycycline. Immunofluorescent staining of lung sections was performed using anti-CHI3L1 and F4/80 antibodies. Co-localization of both staining was observed in the merged picture. Bar represents 20 µm.</p

Prevalence of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma in the United States Across Time

Human papillomaviruses (HPVs) are involved in approximately 5% of all human cancer. Although initially recognized for causing nearly all cases of cervical carcinoma, much data has now emerged implicating HPVs as a causal factor in other anogenital cancers as well as a subset of head and neck squamous cell carcinomas (HNSCCs), most commonly oropharyngeal cancers. Numerous clinical trials have demonstrated that patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) have improved survival compared to patients with HPV– cancers. Furthermore, epidemiological evidence shows the incidence of OPSCC has been steadily rising over time in the United States. It has been proposed that an increase in HPV-related OPSCCs is the driving force behind the increasing rate of OPSCC. Although some studies have revealed an increase in HPV+ head and neck malignancies over time in specific regions of the United States, there has not been a comprehensive study validating this trend across the entire country. Therefore, we undertook this meta-analysis to assess all literature through August 2013 that reported on the prevalence of HPV in OPSCC for patient populations within the United States. The results show an increase in the prevalence of HPV+ OPSCC from 20.9% in the pre-1990 time period to 51.4% in 1990–1999 and finally to 65.4% for 2000–present. In this manner, our study provides further evidence to support the hypothesis that HPV-associated OPSCCs are driving the increasing incidence of OPSCC over time in the United States

Stimulatory effect of CHI3L1 on tumor cells <i>in vitro</i>.

<p><b>A)</b> Purity of recombinant CHI3L1-Flag fusion protein (upper arrow); <b>B)</b> LLC cell proliferation treated with GST or CHI3L1-GST fusion protein; <b>C)</b> The apoptotic activity of LLC cells treated with GST or CHI3L1-GST fusion protein by Annexin V labeling assay. *, p<0.05, **, P<0.01.</p

ELISA analysis of CHI3L1 protein in serum of human lung cancer patients.

<p>Top: CHI3L1 protein concentrations in human serum. Bottom: ROC (Receiver Operating Characteristic) curve analysis to determine the area under the curve (AUC). Mean ± SD in control (n>30): 17.3±7.8. Mean ± SD in adenocarcinoma (n>30): 66.9±64.8. Mean ± SD in squamous carcinoma (n>30): 69.3±69.0. Mean ± SD in small cell cancer (n>30): 56.3±58.8. The gray lines represent the mean values. Control: Normal human without cancer.</p

Western Blot analysis of Stat3C-Flag and CHI3L1 protein in CCSP-rtTA/(TetO)₇-CMV-Stat3C mice.

<p><b>A)</b> Expression of Stat3C-Flag in the whole lung of CCSP-rtTA/(tetO)7-CMV-Stat3C double-transgenic mice. Actin was used as control. WT: wild type mouse lungs; -Dox: doxycycline untreated bouble transgenic mouse lungs; +Dox1 & +Dox2: doxycycline treated mouse lungs. <b>B)</b> Expression of CHI3L1 protein in BALF of CCSP-rtTA/(TetO)₇-CMV-Stat3C double-transgenic mice. Lane 1–3, doxycycline-untreated mice (Dox-); Lane 4–6, doxycycline-treated mice without showing lung tumor (Dox+); Lane 7–10, doxycycline-treated mice showing lung tumor (Lung Cancer).</p

ELISA analyses of CHI3L1 protein in BALF and serum of CCSP-rtTA/(TetO)₇-CMV-Stat3C bitransgenic mice.

<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. Mean ± SD in BALF (n>13), DOX -: 8.8±10.0, DOX +: 100.0±49.0, Cancer: 151.8±67.3. Mean ± SD in serum (n>13), DOX -: 6.2±3.7, DOX +: 33.5±35.6, Cancer: 159.0±90.0. The gray lines represent the mean values.</p

ELISA analyses of CHI3L1 protein in BALF and serum of regional inflammation-induced lung tumor mice.

<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. <b>A)</b> CCSP-rtTA/(TetO)₇-CMV-MMP12 mice. Mean ± SD in BALF (n>7), DOX -: 49.6±22.8, DOX +: 49.4±18.1, Cancer: 159.7±22.4. Mean ± SD in serum (n>7), DOX -: 18.6±10.9, DOX +: 18.2±4.6, Cancer: 61.4±33.5. The gray lines represent the mean values; <b>B)</b> CCSP-rtTA/(TetO)₇-CMV-Api6 mice. Mean ± SD in BALF (n>3), DOX -: 82.4±37.1, DOX +: 93.8±23.0, Cancer: 409.8±49.2. Mean ± SD in serum (n>3), DOX -: 14.0±7.2, DOX +: 30.7±43.1, Cancer: 295.2±194.0. The gray lines represent the mean values.</p

Immunohistochemical staining of CHI3L1 protein in the lung of inflammation-induced tumor mice.

<p><b>A)</b> Immunohistochemical staining in the lungs of doxycycline-treated or untreated CCSP-rtTA/(TetO)₇-CMV-Stat3C mice; <b>B)</b> Immunohistochemical staining of tumor regions in the lungs of doxycycline-treated CCSP-rtTA/(TetO)₇-CMV-MMP12 mice, c-fms-rtTA/(TetO)₇-CMV-MMP12 mice, and c-fms-rtTA/(TetO)₇-CMV-Api6 mice. -Dox: doxycycline-untreated mice; +Dox: doxycycline-treated mice.</p

ELISA analyses of CHI3L1 protein in BALF and serum of systemic inflammation-induced lung tumor mice.

<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. <b>A)</b> c-fms-rtTA/(TetO)₇-CMV-MMP12 mice. Mean ± SD in BALF (n>7), DOX -: 17.7±13.8, DOX +: 42.1±67.9, Cancer: 70.9±36.5. Mean ± SD in serum (n>7), DOX -: 39.1±25.6, DOX +: 57.7±55.5, Cancer: 232.3±110.6. The gray lines represent the mean values; <b>B)</b> c-fms-rtTA/(TetO)₇-CMV-Api6 mice. Mean ± SD in BALF (n>6), DOX -: 69.6±16.6, DOX +: 73.2±28.1, Cancer: 189.9±47.2. Mean ± SD in serum (n>6), DOX -: 25.2±7.3, DOX +: 21.0±11.7, Cancer: 69.5±19.1. The gray lines represent the mean values.</p

Immunofluorescence analysis of CARM1 localization in human cell lines.

<p>(a, b) Localization of CARM1FL (E15) and total CARM1 (E16) in MDA-MB-231 cells. (c, d) Localization of CARM1FL (E15) and total CARM1 (E16) in BG-1 cells. (b) and (d) are quantification of immunofluorescence signals in cytoplasm and nucleus. DAPI: nuclear stain (blue). Phalloidin: cytoskeleton/actin probe (red). Student’s t test was used for statistical analysis. n = 3, *p < 0.05.</p