Histochemical and Immunohistochemical Study of α-SMA,Collagen, and PCNA in Epithelial Ovarian Neoplasm

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms.     

Expressions of Beta-Catenin,SUFU and VEGFR-2 Proteins in Medulloblastoma

Objective:to investigate the expressions of beta-catenin,SUFU and VEGFR-2 proteins in medulloblastoma.Methods:Immunohistochemical staining with SP method was conducted to determine the expressions of beta-catenin,SUFU and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues.Results:the abnormal expression rates of beta-catenin and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue.While the positive expression of SUFU gene in medulloblastoma was significantly lower than that in 10 normal cerebellar tissues.A significant negative correlation was found between beta-catenin and SUFU proteins and a positive correlation between beta-catenin and VEGFR-2 was found in medulloblastoma.Conclusion:Beta-catenin,VEGFR-2 and SUFU have important effects on the pathogenesis and development of medulloblastoma.     

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-Differences in Etiology,Epidemiology and Prevention

In Germany,esophageal carcinoma is one of the ten most frequent causes of death.Normallythe disease is found in men over the age of 50.Although squamous cell carcinoma (SCC) of the esophagushas been more commonly diagnosed over the past 30 years,there is increasing incidence of esophagealadenocarcinoma (AC) in Western industrialized countries.For SCC the known etiological risk factorsare nicotine and alcohol abuse.For AC,they are moderate nicotine and alcohol consumption as well asgastro-esophageat reflux and obesity.     

Age–incidence patterns of primary CNS tumors in children,adolescents, and adults in England

Around 25% of all tumors in those 0–14 years of age and 9% in those 15–24 years of age involve the CNS. They are the most common cause of cancer-related deaths in both age groups. In adults 25–84 years of age, the proportion of CNS tumors is 2%; 5-year overall survival is 10%–15%; and survivors have considerable morbidity. Comprehensive up-to-date population-based incidence data on these tumors are lacking. We present incidence rates for primary CNS tumors based on data derived from the high-quality national cancer registration system in England. A total of 54,336 CNS tumors of malignant, benign, and uncertain behavior were registered across the whole of England from 1995 through 2003. The age-standardized rates for all ages (0–84 years) was 9.21 per 100,000 person-years. This is higher than previously reported for England because it includes nonmalignant CNS tumors and hence gives a more accurate picture of burden of disease. The age-standardized rates for those 0–14 years of age, 15–24 years of age, and 25–84 years of age were 3.56, 3.26, and 14.57 per 100,000 person-years, respectively. In this article, we describe the changing patterns in the epidemiology of primary CNS tumors in these three age groups with respect to sex, tumor behavior, and histology using the current WHO classification. This information will provide a reference for future studies nationally and internationally and make comparisons relevant and meaningful.     

Expression of E2F-1, Rb and ER in Peripheral Papilloma and Ductal Carcinoma in Situ of the Breast and its Significance

OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the canceration of Peri-PM. METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia (Peri-PM with ADH) and 60 DCIS. Normal breast tissues were selected as a control group. RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%, 46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%. Significant differences were found among the 3 groups (Peri-PM, Peri-PM with ADH and DCIS) (P<0.05). Significant differences existed between any 2 groups (P<0.05) except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS (P>0.05). The expression of E2F-1 was nega- tively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline. CONCLUSION The interaction of the 3 indexes studied may play an im- portant role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.     

Incidence,survival, and mortality of cancer in children and young adolescents in Belgium and the Netherlands in 2004–2015: A comparative population-based study

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0–14 years) and young adolescents (15–17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan–Meier method. During 2004–2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010–2015: SRR = 1.3, 95% CI 1.0–1.6). Five-year survival of all malignant cancers was comparable in 2010–2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004–2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010–2015, and for neuroblastoma in both periods (2004–2009: BE = 76%, NL = 64%; 2010–2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004–2009 (SRR = 0.9, 95% CI 0.7–1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010–2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.     

Expressions of Beta-Catenin, SUFU and VEGFR-2 Proteins in MeduUoblastoma

Objective： to investigate the expressions of beta-catenin, SUFU and VEGFR-2 proteins in medulloblastoma. Methods： Immunohistochemical staining with SP method was conducted to determine the expressions of beta-catenin, SUFU and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues. Results： the abnormal expression rates of beta-catenin and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue. While the positive expression of SUFU gene in medulloblastoma was significantly lower than that in 10 normal cerebellar tissues, A significant negative correlation was found between beta-catenin and SUFU proteins and a positive correlation between beta-catenin and VEGFR-2 was found in medulloblastoma. Conclusion： Beta-catenin, VEGFR-2 and SUFU have important effects on the pathogenesis and development of medulloblastoma.     

Citizenship,length of stay,and screening for breast,cervical, and colorectal cancer in women, 2000–2010

Background

Two factors jointly account for significant gaps in access to health care among immigrants who are present in the U.S.—legal status, and length of residence. The objective of this study is to examine the association between citizenship and length of residence in the U.S. and cancer screening (breast, cervical, and colorectal) among women.

Methods

We analyzed 11 years (2000–2010) of consolidated data from the Medical Expenditure Panel Survey linked with the National Health Interview Survey. Multivariate analyses compared cancer screening among U.S.-born citizens (n?=?58,484), immigrant citizens (n?=?8,404), and immigrant non-citizens (n?=?6,564).

Results

Immigrant non-citizens living in the U.S. for less than 5 years were less likely to receive guideline-concordant breast (OR?=?0.68 [0.53–0.88]), cervical (OR?=?0.65 [0.54–0.78]), and colorectal (OR?=?0.31 [0.19–0.50]) cancer screening compared to U.S.-born citizens. Immigrant citizens and non-citizens living in the U.S. for 5 years or more had higher odds of being screened for breast and cervical cancer compared to U.S.-born citizens; (OR?=?1.26 [1.13–1.41] and OR?=?1.17 [1.06–1.29]) for immigrant citizens, (OR?=?1.28 [1.13–1.45] and OR?=?1.23 [1.09–1.38]) for non-citizens. Immigrant non-citizens living in the U.S. for 5 years or more had lower odds of being screened for colorectal cancer compared to U.S.-born citizens (OR?=?0.76 [0.65–0.90]).

Conclusions

Based on these findings, duration mandates in immigration policy may indirectly influence future pathways to preventive health care and cancer disparities disproportionately affecting immigrant women. We suggest that limits of duration mandates be reevaluated, as they may offer pathways to preventive health care for this vulnerable population, and prevent future cancer disparities.

     

Expression and prognostic value of VEGFR-2, PDGFR-β, and c-Met in advanced hepatocellular carcinoma

Background

We explore the clinical and prognostic significance of expression of vascular endothelial growth factor receptor (VEGFR)-2, platelet-derived growth factor receptor (PDGFR)-β, and c-Met in patients with hepatocellular carcinoma (HCC).

Methods

The expression of VEGFR-2, PDGFR-β, and c-Met were determined by immunohistochemical examination of the tissues of 93 HCC patients. The relationships of these markers with clinicopathological factors and prognosis were then analyzed.

Results

High expression of VEGFR-2, PDGFR-β, and c-Met was found in 86%, 19.4%, and 80.6% of patients, respectively. Expression of VEGFR-2 correlated with gender (P = 0.044), hepatitis B surface antigen positivity (P = 0.024), degree of tumor differentiation (P = 0.023), and hepatic cirrhosis (P = 0.026). Expression of PDGFR-β correlated with alpha-fetoprotein level (P = 0.029), tumor size (P = 0.033), and hepatic cirrhosis (P = 0.023). No significant correlations were identified between expression of c-Met and clinicopathological factors. Expression of PDGFR-β correlated with overall survival (P = 0.046) and expression of c-Met correlated with progression-free survival (P = 0.01).

Conclusions

We found that in patients with HCC, high expression of VEGFR-2 correlates with chronic hepatitis B virus infection and hepatic cirrhosis. High expression of PDGFR-β is a predictor of poor prognosis. High expression of C-Met may predict therapeutic effectiveness of sorafenib in HCC patients.     

Population-based Survival from Cancers of Breast,Cervix and Ovary in Women in Mumbai,India

Background: Breast, cervix and ovarian cancers contribute more than 45% of the total in women in Mumbai ‍and survival proportions for these neoplasms are very high in most developed populations in the World. The authors ‍here report and discuss the population-based survival for these cancers in Mumbai, India. ‍Methods: Follow-up information on 4865 cancers of breast, cervix and ovary, registered in the Mumbai Population ‍Based Cancer Registry for the period 1992-1994 was obtained by a variety of methods, including matching with ‍death certificates from the Mumbai vital statistics registration system, postal/telephone enquiries, home visits and ‍scrutiny of medical records. The survival for each case was determined as the duration between the date of diagnosis ‍and date of death, date of loss to follow-up or the closing date of the study (December 31st, 1999). Cumulative ‍observed and relative survival was calculated by the Hakulinen Method. For comparison of results with other ‍populations, age-standardized relative survival (ASRS) was calculated by directly standardizing age specific relative ‍survival to the specific age distributions of the estimated global incidence of major cancers in 1985. The log rank test ‍was used in univariate analysis to identify the potentially important prognostic variables. The variables showing ‍statistical significance in univariate analysis were introduced stepwise into a Cox Regression model to identify the ‍independent predictors of survival. ‍Results: The 5-year relative survival rates were 46.2% for breast, 47.7% for the cervix and 25.4% for the ovary. ‍Higher survival was observed for those younger than 35 years for all these three sites. For each, survival declined ‍with advancing age. Single patients who remained unmarried had better survival. For all sites Muslims had a better ‍and Christians a lower survival as compared to Hindus. Education did not appear to be of significance. Survival ‍decreased rapidly with advancing clinical extent of disease for all sites. With localized cancer, 5-year rates ranged ‍from 54.7% to 69.3%, for regional spread 20.4% to 41.6% and distant metastasis not a single site recorded more ‍than 5%. On multivariate analysis, age and extent of disease emerged as independent predictors of survival for all ‍the sites. ‍Conclusion: All the sites included in the study demonstrated moderate survival rates with significant variation. ‍Comparison with other populations revealed lower survival rates as compared to developed countries, particularly ‍for breast and ovary. In Indian populations survival proportions did not show much variation for these cancers. ‍Early detection and treatment are clearly important factors to reduce the mortality from these cancers. ‍     

Expression of TGF-β1, Snail, E-cadherin and N-cadherin in Gastric Cancer and Its Significance

OBJECTIVE To investigate the expression of TGF-β1,Snail,E-cad-herin and N-cadherin in gastric cancer(GC),and to examine its relationship to malignant features of the tumors. METHODS The expression of TGF-β1,Snail,E-cadherin and N-cadherin proteins was detected in GC and adjacent tissues by immunohistochemical staining,and compared with the clinico-pathological data. RESULTS Positive rates of expression for TGF-β1,Snail,E-cadherin and N-cadherin were 63.5%,83.3%,37.5%and 44.8%in GC,and 28.8%, 41.3%,100%,11.3%in adjacent tissues,respectively.The expression of all four proteins showed a significant difference between the GCs and adjacent tissues(P<0.05).The positive rate of TGF-β1,Snail and N-cadherin,or the negative rate of E-cadherin expression was significantly related to the differentiated degree,histological type,invasion and metastasis of GC.In addition,the expression of N-cadherin was positively related to that of TGF-β1, but negatively related to that of E-cadherin.There was negative correlation between expression of E-cadherin and TGF-β1 and Snail in GC(P<0.05). CONCLUSION The over-expression of TGF-β1 and Snail and decreased expression of E-cadherin and the abnormal expression of N-cad-herin were involved in the process of invasion and metastasis of GC.The data showed that E-cadherin might switch to N-cadherin.TGF-β1 and Snail might play a fundamental role in the process.     

Concomitant secretion of calcitonin, β-endorphin and ACTH from medullary thyroid carcinoma in vivo and in vitro

The present study was performed to investigate the possible synthesis of a common precursor molecule for calcitonin (CT), adrenocorticotropin (ACTH) and β-lipotropin (β-LPH)/β-endorphin (β-EP) by the human medullary thyroid carcinoma (MTC). In a patient with MTC but without Cushing's syndrome, the response of plasma CT, ACTH and cortisol levels to a calcium infusion, lysine vasopressin (LVP) and dexamethasone were measured. A parallel increase of these hormones in response to calcium and LVP was seen, while there was a paradoxical increase of CT during dexamethasone infusion. Incubation of MTC fragments obtained at surgery showed a significant correlation of the secretion of CT, ACTH and β-LPH/β-EP in response to calcium, LVP and dexamethasone. The concomitant release of these hormones in vivo and in vitro could be compatible with the synthesis of a common precursor molecule for CT, ACTH and β-LPH/β-EP in MTC, although this was not substantiated by gel-chromatography of the tumor extract. Corticotropin releasing factor, a regulator of the normal processing of pro-opiococorticoid precursor molecule in the anterior pituitary gland, is also able to activate ACTH, β-LPH/β-EP and calcitonin secretion from the malignant C-cell of the thyroid.     

Expression of cGMP-dependent protein kinase, PKGIα, PKGIβ, and PKGII in malignant and benign breast tumors

Cyclic GMP-dependent protein kinases (PKG) constitute a small family of enzymes that are encoded by two genes. Two major forms of PKG have been identified in mammalian cells, PKG I and PKG II. In addition, there are two splice variants of PKG I, which are designated as I?? and I??. There are increasing evidences that PKG can play an important role in the inhibition of cell proliferation and induction of apoptosis. In our previous studies, the inhibitory effects of cGMP/PKG on the cell growth were indicated using breast cancer cell lines. Accordingly, the present study was designed to compare the expression levels of three PKG isoforms in normal, benign, and malignant breast tissues. The expression level of PKG isoforms was assayed using quantitative real-time RT-PCR. The correlation between relative expression of PKG isoforms and clinicopathological characteristics were also analyzed. Downregulation of PKG isoforms was observed in the malignant and benign tumors when compared to those of respective normal tissues. No significant correlation was found between PKGI??, PKGI??, and PKGII expression and clinicopathological features. The present study is the first to evaluate the expression level of PKG isoforms PKGI??, PKGI??, and PKGII in the malignant and benign breast tumors. Reduction in the PKG expression is an important evidence to support the antitumor activity of this enzyme in vivo.     

Fludarabine,Cyclophosphamide, and Rituximab in Salvage Therapy of Waldenström's Macroglobulinemia

The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up.     

Role of β-catenin in cisplatin resistance,relapse and prognosis of head and neck squamous cell carcinoma

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis.

Methods

In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample. Kaplan-Meier analyses were performed to correlate β-catenin expression with the survival and prognosis of HNSCC patients. In addition, chemo-resistance, DNA damage response and DNA repair capacities were evaluated in HNSCC-derived cell lines through LiCl-mediated up-regulation and siRNA-mediated silencing of β-catenin expression.

Results

We observed β-catenin up-regulation in cut margin areas of recurrent patients compared to their corresponding tumor regions, which subsequently could be associated with poor prognosis. In addition, we found that LiCl-mediated up-regulation of β-catenin in HNSCC-derived cells led to cisplatin resistance, evasion of apoptosis, enhanced DNA repair and enhanced migration. The effects of β-catenin silencing correlated with its putative role in chemo-resistance and DNA damage response.

Conclusion

From our results we conclude that β-catenin may contribute to HNSCC therapy resistance and disease relapse. As such, β-catenin may be explored as a therapeutic target along with conventional therapeutics.

     

Prospective study of serum retinol, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China

Objective: This study examined the relationship between pretrial serum concentrations of retinol, -carotene, -cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. Methods: We used a stratified case–cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Results: Median values in our cohort were low for serum retinol (33.6 g/dl), -carotene (4.3 g/dl), and -cryptoxanthin (3.5 g/dl) , but were high for lutein/zeaxanthin (40.0 g/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83–0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63–0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31–0.96). For -cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76–1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0–1.3) with increasing concentration of serum lutein/zeaxanthin. Conclusions: In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.     

Expression of Wnt-1, beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

Objective： To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1, beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results： The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell （P〈0.05）. The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell （P〈0.05）. A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor （P〈0.05）. A significant difference of expressions of Beta-catenin and C-myc was found between serous and mucinous tumors （P〈0.05）. Conclusion： The abnormal expression of Wnt-1, beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.     

Synergistic effects of imatinib and carboplatin on VEGF, PDGF and PDGF-Rα/ß expression in squamous cell carcinoma of the head and neck in vitro

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. The development of new treatment modalities in order to improve long-term survival of patients with HNSCC is imperative. Numerous studies have demonstrated that carcinogenesis and tumor cell dissemination is influenced by the tumor microenvironment. The protein-kinase-receptors (PTKs) are essential elements of the intracellular signal transduction pathway and regulate cell growth, development and apoptosis. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, invasion is regulated by a variety of angiogenic factors, such as PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor) and their respective tyrosine kinase receptors (PDGF-R and VEGF-R). They present promising targets for anti-cancer therapy through abrogation of impaired signaling pathways. Indeed, imatinib, a small molecule drug targeting these protein kinases, has antiproliferative effects in several cancer types. The purpose of this study was to investigate the potential synergism of imatinib and carboplatin on the expression of PDGF, PDGF-R α/? and VEGF in different HNSCC cell lines. Several tumor cell lines were subjected to increasing concentrations of carboplatin (3 and 7.5 μmol/l) and imatinib (18 and 30 μmol/l) and ELISA, immunohistochemical methods and RQ-PRC after 48, 72, 120 and 240 h were used to assess their expression levels. While PDGF-Rα/? expression was unimpaired at lower imatinib concentrations (18 μmol/l), PDGF-Rα/? expression was suppressed at 30 μmol/l, and suppression was enhanced by the presence of carboplatin. By RQ-PCR, a significant reduction of PDGF-Rα/? expression was detected (p<0.5). We observed explicit significant reduction in VEGF levels with increasing concentrations of imatinib and with the combination of the two chemotherapeutic drugs (p<0.5). We report for the first time evidence of synergism of imatinib and carboplatin in suppressing VEGF, PDGF and PDGF-Rα/? expression in HNSCC.     

Trends in treatment and outcomes of pediatric craniopharyngioma, 1975–2011

Background

Craniopharyngioma tumors and their treatment can lead to significant long-term morbidity due to their proximity to vital structures. The optimal treatment has been debated for many years. We aimed to review the long-term outcomes of children treated for craniopharyngioma in our institution over the past decade and describe trends in treatment and outcomes over the past 3 decades.

Methods

Charts of children with craniopharyngioma treated and followed at The Hospital for Sick Children between 2001 and 2011 were reviewed. Data regarding findings at diagnosis, treatment, and long-term outcomes were analyzed. Comparison was made with previously published data from our institution.

Results

Data from 33 patients are included; mean age at treatment, 10.7 ± 4.8 years. In 18 children (55%), the initial surgical approach was tumor cyst decompression with or without adjuvant therapy, compared with only 0–2% in the preceding decades (P < .01). Diabetes insipidus occurred in 55% of children and panhypopituitarism in 58% compared with 88% (P < .01) and 86% (P < .01), respectively, in the previous 10 years. Overall, there was a 36% reduction in the number of children who developed severe obesity compared with the preceding decade. Body mass index at follow-up was associated with body mass index at diagnosis (P = .004) and tumor resection as an initial treatment approach (P = .028).

Conclusions

A shift in surgical treatment approach away from gross total resection has led to improved endocrine outcomes. This may have beneficial implications for quality of life in survivors.