Squamous Cell Carcinoma Levels Research Articles

Socioeconomic status and non-melanoma skin cancer: A nationwide cohort study of incidence and survival in Denmark

Background: The two main types of non-melanoma skin cancer differ with the pattern of exposure to ultraviolet radiation (UVR): basal cell carcinoma (BCC) appears to be more closely related to intermittent solar exposure and sunburn, while the risk for squamous cell carcinoma (SCC) is a result of lifetime cumulated exposure to UVR. As these exposures may differ by social position, we investigated its role in the risk for and survival after BCC and SCC diagnosed in Denmark in 1994–2006 with follow-up through 2006. Methods: The analyses were based on 52,166 cases of BCC and 5033 cases of SCC in a cohort of 3.7 million people born between 1925 and 1976 and residing in Denmark in 1992–2006. Information on cancer cases and socioeconomic indicators were obtained from population-based registries. We used log-linear Poisson regression models to estimate incidence rate ratios and cumulative relative survival to estimate survival up to 10 years after the first incident cases of BCC and SCC. Results: High socioeconomic status, measured by both education and disposable income, was strongly associated with a higher risk for BCC, whereas there was no association between SCC and educational level and only a weak association with income. In general, relative survival after BCC was better than after SCC; the pattern of survival was not affected by socioeconomic indicators. Conclusions: The observed pattern of social status and risk for non-melanoma skin cancer differed substantially for the two cancer types, supporting the hypothesis that they may have different aetiologies.

Polymorphisms of FAS and FAS ligand genes and risk of skin cancer

Polymorphisms of FAS and FAS ligand genes and risk of skin cancer

Possible role of telomerase and sFas in pathogenesis of various bladder lesions associated with schistosomiasis

Objectives To find the role of telomerase and sFas in the pathogenesis of various bladder lesions associated with schistosomiasis and to correlate the results with clinicopathological parameters. Design and methods One hundred bladder samples were taken, including 65 cases with bladder cancer, 25 cases with chronic cystitis and 10 samples from normal bladder tissue as control. Telomerase activity was measured using TRAP and hTERT techniques. Also, sFas was detected by ELISA technique in serum of all patients. Results TRAP activity was detected in 78.5%; there was a significant increase in the number of positive cases in schistosomal urothelial carcinoma (TCC) and squamous cell carcinoma (SCC) compared to control and non-schistosomal urothelial carcinoma at ( p < 0.01 for each). TRAP activity was positive in 100% of high grade urothelial carcinoma compared to low grade and 92% positive in invasive tumors compared to non invasive tumors. hTERT protein was detected in 75.4% of bladder cancer cases; there was a significant increase in the number of positive cases in schistosomal urothelial carcinoma and SCC compared to control and non schistosomal urothelial carcinoma ( p < 0.01 for each). hTERT was positive in 100% of high grade and invasive TCC. sFas was detected in 64.6% in bladder cancer cases; there was a significant increase in the number of positive cases in SCC compared to control and non-schistosomal urothelial carcinoma. Conclusion There is an increase in telomerase activity and over-expression of hTERT proteins in schistosomal associated bladder cancer (SABC) in comparison to non schistosomal associated bladder cancer (non SABC). Also, there is an increase in sFas level in SCC compared to other the groups. Both, telomerase activity by TRAP and hTERT and sFas may be of significance in the development of SABC. They may also be useful markers to identify bladder carcinoma through telomerase inhibition.

Squamous Cell Carcinoma Antigen in Patients with Locally Advanced Cervical Carcinoma Undergoing Preoperative Radiochemotherapy: Association with Pathological Response to Treatment and Clinical Outcome

Objective: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. Methods: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. Results: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. Conclusions: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.

A Combination of Serum Tumor Markers Identifies High-Risk Patients with Early-Stage Squamous Cervical Cancer

We aimed to investigate whether pretreatment serum levels of squamous cell carcinoma (SCC) antigen (SCC-Ag), cytokeratin 19 (CYFRA 21-1) and two mucins (CA 15-3 and CA 125) identify patients with occult disease in early-stage SCC of the cervix. Therefore, pretreatment serum samples were obtained from 78 patients with SCC of the cervix (52 IB, 9 IIA and 18 IIB), and tumor markers were measured with commercial immunoassays. SCC-Ag, CYFRA 21-1 and CA 15-3 (analyzed as continuous variables) were significantly associated with overall (OS) and disease-free survival (DFS) in univariate analysis (p < 0.001 in all cases). Multivariate analysis identified lymph node status as the strongest predictor for OS and DFS (p < 0.001 and p = 0.001, respectively), followed by CYFRA 21-1 (p = 0.060 and p = 0.027, respectively) and CA 15-3 (p = 0.082 and p = 0.017, respectively). Clinical cutoff values for each marker were defined by maximizing the log-rank statistics for OS in the total population: 1.1 µg/l for SCC-Ag (n = 47, 60.3%), 1.4 µg/l for CYFRA 21-1 (n = 47, 60.3%), 40 U/ml for CA 15-3 (n = 11, 14.1%) and 30 U/ml for CA 125 (n = 10, 12.8%). Stage IB patients with positive SCC-Ag and CYFRA 21-1 had significantly lower OS (mean 8.3 years, 95% confidence interval, CI, 5.8–10.7 years) and DFS (mean 7.3 years, 95% CI 4.6–10 years) than all other stage IB patients (OS, mean 14.5 years, 95% CI 13.5–15.5 years; DFS, mean 13.9 years, 95% CI 12.5–15.4 years). Stage IB patients with tumors <4 cm or with negative lymph nodes and positive SCC-Ag and CYFRA 21-1 had significantly poorer OS and DFS compared to all other patients in the same group. Elevated levels of both CA 125 and CA 15-3 (3 patients) were associated with an extremely poor prognosis. In conclusion, a combination of SCC-Ag and CYFRA 21-1 may help to identify early-stage cervical cancer patients with occult disease requiring adjuvant therapy.

Tumorzelltod im Spiegel der SCC-Antigentiter?*

The serum levels of squamous cell carcinoma (SCC) associated antigen are related to the course of the therapy in 91 cases of advanced head and neck cancers. Without statistical significance the findings may lead to the following statements: 1. Serum levels below 2 ng/ml before treatment are not related to tumour growth. 2. Serum levels above 2 ng/ml before treatment are likely to be regarded as tumour-associated. 3. High and low level curves of not operated patients show a quantitatively different reaction to the course of a combined simultaneous radiochemotherapy. 4. Initially increasing serum levels under combined therapy may be interpreted as related to cell death or result of a production or proliferation stimulus. 5. High serum levels and low serum levels in tumour patients might be regarded as an expression of different biological activities in the tumour. 6. The comparison of the survival rates of high level tumours to low level tumours raises the question as to whether this different biological activity might be related to clinical malignancy.

Squamous Cell Carcinoma Antigen in Follow-Up of Cervical Cancer Treated With Radiotherapy: Evaluation of Cost-Effectiveness

The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. Our results have shown that a simplified diagnostic approach, including the SCC assay and gynecologic examination, can detect a high rate of recurrence from cervical cancer, with a very favorable cost-effective profile.

Overexpression of Dicer in Precursor Lesions of Lung Adenocarcinoma

Differential microRNA (miR) expression is described in non-small cell lung carcinoma. miR biogenesis requires a set of proteins collectively referred to as the miR machinery. In the proposed multistep carcinogenesis model, peripheral adenocarcinoma of the lung develops from noninvasive precursor lesions known as atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). The gene array analysis of BAC and adenocarcinoma showed a transient up-regulation of Dicer (a key effector protein for small interfering RNA and miR function) and PACT along with down-regulation of most genes encoding miR machinery proteins. Immunohistochemically, Dicer was up-regulated in AAH and BAC and down-regulated in areas of invasion and in advanced adenocarcinoma. A fraction of adenocarcinomas lose Dicer as a result of deletions at the Dicer locus. Expanded immunohistochemical and Western blot analysis showed higher Dicer level in squamous cell carcinoma (SCC) of the lung when compared with adenocarcinoma. Other proteins of the RNA-induced silencing complex (RISC; SND1, PACT, and FXR1) were also present at higher levels in a SCC cell line when compared with an adenocarcinoma cell line. In conclusion, the stoichiometry of miR machinery and RISC depends on histologic subtype of lung carcinoma, varies along the AAH-BAC-adenocarcinoma sequence, and might explain the observed abnormal miR profile in lung cancer. The status of the endogenous miR machinery in various histologic subtypes and stages of lung cancer may help to predict the toxicity of and susceptibility to future RNA interference-based therapy.

Visual Grading System, Blood Flow Index, and Tumor Marker SCC Antigen as Prognostic Factors in Invasive Cervical Carcinoma

The purpose of this study was to develop a new visual grading system for the vascular ratio, to assess the correlation of the prognostic significance of the visual grading system, tumoral blood flow velocity and squamous cell carcinoma (SCC) antigen serum levels in invasive SCC of the cervix. A total of 117 patients with invasive cervical carcinoma were enrolled for the assessment of vascular grading and tumor flow using transvaginal ultrasound with power Doppler angiography (TV-PDA) before treatment. The modified visual grading system of the vascular ratio (grades 1 to 3) and six blood flow characteristics of tumor vessels (pulsatility index, resistance index, peak systolic velocity, end-diastolic velocity, time-averaged maximum velocity, vascular index) were measured by TV-PDA. In addition, serum levels of SCC antigen were randomly obtained in 74 patients with invasive cervical SCC (stages Ia to IIIb) before treatment. The modified visual grading system of the vascular ratio significantly correlated with pretreatment SCC antigen serum levels ( p < 0.05) and intratumoral resistance index values ( p < 0.05, r 2 = 0.49) from multiple regression analysis in 71 patients with invasive SCC of the cervix. Modified visual grading of the vascular ratio negatively correlated with intratumoral resistance index values (Pearson's correlation coefficient, r = −0.571, p = 0.001), but positively correlated with pretreatment serum levels of SCC antigen ( r = 0.296, p = 0.012). In addition, this modified vascularity grading positively correlated with FIGO stage ( r = 0.336, p = 0.004) by correlation analysis. The modified visual grading system of the vascular ratio is a valuable sonographic marker in assessing invasive cervical carcinoma. The three major advantages of this semi-quantitative analysis are ease of discrimination, immediate results, and avoiding wasting time. This semi-quantitative analysis with pretreatment SCC antigen serum levels are two effective markers for assessing invasive cervical carcinoma.

Cyclin A and beta-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin

Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of beta-catenin, the molecule involved in cell-cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. To determine cyclin A and beta-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin-biotin technique using antibodies to cyclin A and beta-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC-11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for beta-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. Diffuse cyclin A presence was observed more frequently in BD than in AK (P < 0.0001) or SCC (P = 0.0002), and in SCC-PD compared with SCC-WD (P < 0.0001) or SCC-MD (P = 0.0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant (P < 0.0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 (P < 0.0001). Cyclin A LI was significantly lower (P < 0.05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent beta-catenin membranous staining was found in 90 cases (81.8%), more often in SCC than in AK (P = 0.03) or in AK and BD grouped together (P = 0.02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous beta-catenin staining showed 36 lesions (32.7%), more frequently SCC than AK (P = 0.003) or AK and BD grouped (P = 0.006), as well as SCC-PD compared with SCC-WD (P = 0.01) and SCC-MD (P = 0.03), whereas all KIN comparisons remained nonsignificant. Aberrant beta-catenin cellular localization demonstrated 28 lesions (25.5%), most often in the basal or peripheral parts and in the lesions with diffuse beta-catenin loss (P = 0.009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous beta-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm (P = 0.03), while all other comparisons between cyclin A or beta-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining (P = 0.001) or with aberrant cellular localization of beta-catenin (P = 0.002). Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced beta-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous beta-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of beta-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions (in situ, partial thickness) are grouped.

Elective Transcervical Superior Mediastinal Lymph Node Dissection For Advanced Laryngeal and Level 4 N3 Squamous Cell Carcinoma

To review our results with elective superior mediastinal lymph node dissections in patients with advanced laryngeal squamous cell carcinoma (SCCA) and overt level 4 adenopathy. Retrospective review. We searched operative case logs for all patients treated with an elective superior mediastinal dissection by the senior author (Y.D.) during a 7-year period. Charts were reviewed for demographic information, prior treatment with chemotherapy or radiotherapy, and pathologic results. Fifty-six patients who underwent elective superior mediastinal lymph node dissection for advanced laryngeal SCCA and overt level 4 adenopathy were reviewed, and superior mediastinal disease was present in 15 of 56 (26.8%) patients. Superior mediastinal nodes were positive in 11 of 42 (26.2%) patients with advanced laryngeal SCCA and 4 of 14 (28.6%) patients with N3 SCCA involving level 4. Patients with SCCA receiving prior chemotherapy and radiotherapy had a significantly higher rate of positive superior mediastinal nodes (10/21 patients, 47.6%) compared with patients without prior therapy (5/35 patients, 14.3%, P = .01, Fisher's exact test). There were no stomal recurrences in 42 patients treated for advanced laryngeal cancer. Elective transcervical superior mediastinal dissection was positive in 26.8% of patients with advanced laryngeal cancer or N3 disease in level 4. A transcervical superior mediastinal dissection may be safely performed without a sternotomy.

Increased nitric oxide levels and iNOS over-expression in oral squamous cell carcinoma

Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated in a number of carcinomas including head and neck squamous cell carcinoma (SCC). However, iNOS levels have not been evaluated specifically in oral cavity SCC, or in the precancerous lesions that progress to oral SCC. Also, NO levels have not been measured in oral precancerous or cancerous tissues. We therefore measured iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral epithelium. A significantly higher percentage of oral SCC specimens showed the highest level of iNOS staining relative to the oral dysplasias and normal oral epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal epithelial controls, P < 0.0001). The positive staining for iNOS was limited to the SCC cells. Production of NO from iNOS was quantified using HPLC and found to be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS mRNA levels and NO production are significantly increased, in oral SCC compared to oral dysplasias and normal epithelial controls. These findings suggest that increased iNOS expression and the generation of high NO levels might have a role in oral SCC development.

Pure primary squamous cell carcinoma of the ovary: a case report and review of the literature

Pure primary squamous cell carcinoma of the ovary: a case report and review of the literature

Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium.

Basic fibroblast growth factor (bFGF) is synthesized by a wide variety of normal and malignant cells. However, bFGF cannot exert its effects unless it gets outside of the cell. Since it lacks a signal sequence to direct secretion, the method by which cells release it remains unclear. A 17 kDa secreted binding protein for bFGF (FGF-BP, HBp-17) is expressed at high levels in squamous cell carcinoma (SCC) and transformed keratinocytes and may act as a chaperone to transport bFGF outside of the cell. In our study, FGF-BP mRNA expression in normal keratinocytes was higher than in 5/5 SCCs. Using a new monoclonal antibody, we demonstrate that FGF-BP can dimerize. Immunoassays demonstrate that normal keratinocytes have a higher level of FGF-BP than SCCs. In normal human squamous epithelium, we observed diffuse, moderate to intense cytoplasmic and membranous expression of FGF-BP. Expression decreased and became focal with disease progression to invasive cancer. Injection of immortalized but non-tumorigenic HaCaT cells transduced with FGF-BP into normal human skin xenografts failed to result in tumors. Transfection of FGF-BP into the SCCs Det 562 and FaDu did not promote tumor growth more than controls, and peri-tumoral microvessel density was lower in FGF-BP-transfected than in control tumors. Taken together, these data suggest that FGF-BP expression in squamous epithelium does not play an important role in progression to invasive carcinoma.

Induction of the Angiogenic Modulator Fibroblast Growth Factor-binding Protein by Epidermal Growth Factor Is Mediated through Both MEK/ERK and p38 Signal Transduction Pathways

Fibroblast growth factor-binding protein (FGF-BP) is a secreted protein that binds and activates fibroblast growth factors (FGF-1 and FGF-2) and induces angiogenesis in some human cancers. FGF-BP is expressed at high levels in squamous cell carcinoma (SCC) cell lines and tumor samples and has been shown to be rate-limiting for the growth of SCC tumors in vivo. In this study, we examine the regulation of FGF-BP by epidermal growth factor (EGF) and the signal transduction mechanisms that mediate this effect. We found that EGF treatment of the ME-180 SCC cell line caused a rapid induction of FGF-BP gene expression. This induction was mediated transcriptionally through the AP-1 (c-Fos/JunD) and CCAAT/enhancer-binding protein elements as well as through an E-box repressor site in the proximal regulatory region of the FGF-BP promoter. Pharmacological inhibition of protein kinase C and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) completely blocked EGF induction of FGF-BP mRNA, whereas inhibition of phosphatidylinositol 3-kinase had no effect. Additionally, both EGF- and anisomycin-induced FGF-BP mRNA was abrogated by inhibition of p38 mitogen-activated protein kinase, demonstrating a role for p38 in the regulation of FGF-BP. Co-transfection of the FGF-BP promoter with dominant negative forms of MEK2, extracellular signal-regulated kinase 2, and p38 significantly decreased the level of EGF induction, whereas expression of a dominant negative c-Jun N-terminal kinase mutant or expression of c-Jun N-terminal kinase inhibitory protein had no effect. Similarly, activation of the p38 pathway by overexpression of wild-type p38 or MKK6 enhanced FGF-BP transcription. These results demonstrate that EGF induction of FGF-BP occurs selectively through dual activation of the stress-activated p38 and the MEK/extracellular signal-regulated kinase mitogen-activated protein kinase pathways, which ultimately leads to activation of the promoter through AP-1 and CCAAT/enhancer-binding protein sites.

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking.

In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg−1protein, P< 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P< 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours. © 2000 Cancer Research Campaign

The Evaluation of SCC (squamous cell carcinoma antigen) Level as a Tumor Marker in Patient with Squamous Cell Carcinoma of the Cervix

The Evaluation of SCC (squamous cell carcinoma antigen) Level as a Tumor Marker in Patient with Squamous Cell Carcinoma of the Cervix

Phorbol Ester-induced Transcription of a Fibroblast Growth Factor-binding Protein Is Modulated by a Complex Interplay of Positive and Negative Regulatory Promoter Elements

Earlier studies from our laboratory showed that a secreted binding protein for fibroblast growth factors (FGF-BP) is expressed at high levels in squamous cell carcinoma (SCC) cell lines. Overexpression studies or conversely reduced expression of FGF-BP by ribozyme targeting have elucidated a direct role of this protein in angiogenesis during tumor development. We have also observed a significant up-regulation of FGF-BP during TPA (12-O-tetradecanoylphorbol-13-acetate) promotion of skin cancer. Here we investigate the mechanism of TPA induction of FGF-BP gene expression in the human ME-180 SCC cell line. We found that TPA increased FGF-BP mRNA levels in a time- and dose-dependent manner mediated via the protein kinase C signal transduction pathway. Results from actinomycin D and cycloheximide experiments as well as nuclear transcription assays revealed that TPA up-regulated the steady-state levels of FGF-BP mRNA by increasing its rate of gene transcription independently of de novo protein synthesis. We isolated the human FGF-BP promoter and determined by deletion analysis that TPA regulatory elements were all contained in the first 118 base pairs upstream of the transcription start site. Further mutational analysis revealed that full TPA induction required interplay between several regulatory elements with homology to Ets, AP-1, and CAATT/enhancer binding protein C/EBP sites. In addition, deletion or mutation of a 10-base pair region juxtaposed to the AP-1 site dramatically increased TPA induced FGF-BP gene expression. This region represses the extent of the FGF-BP promoter response to TPA and contained sequences recognized by the family of E box helix-loop-helix transcription factors. Gel shift analysis showed specific and TPA-inducible protein binding to the Ets, AP-1, and C/EBP sites. Furthermore, distinct, specific, and TPA-inducible binding to the imperfect E box repressor element was also apparent. Overall, our data indicate that TPA effects on FGF-BP gene transcription are tightly controlled by a complex interplay of positive elements and a novel negative regulatory element.

Expression of glutathione S-transferase activity and glutathione content in squamous cell carcinoma of bladder associated with schistosomiasis in a population in Egypt.

The present study was designed to describe the expression of the glutathione S-transferase/glutathione system in squamous cell carcinoma of the bladder in a population in Egypt. The glutathione-S transferase activity was significantly higher in bladder cancer specimens (n = 40) in comparison with schistosomiasis cystitis tissue (n = 42) (4-fold, p = 1 x 10(-12)) and with healthy control samples (n = 9) (10-fold, p = 1 x 10(-6)). The glutathione content was also significantly higher in bladder cancer than in cystitis tissue (2-fold, p = 8 x 10(-6)) and in control samples (6-fold, 8 x 10(-6)). When control mucosa and cystitis samples were compared, 2-fold increased values were obtained for glutathione-S transferase (p = 4 x 10(-3)) and glutathione (p = 1 x 10(-3)) in schistosomiasis bladder tissue. Results describe an over-expression of glutathione-S transferase and glutathione levels in squamous cell carcinoma of the bladder, and indicate a possible role in chemoresistance to pharmacological therapy.