Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma

The epidermal growth factor receptor (EGFR)–RAS–RAF–mitogen-activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR , ErbB2 , and K-ras . Exons encoding the hot-spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18–23), as well as exons 1 and 2 of K-ras were amplified by polymerase chain reaction and sequenced directly. EGFR expression was also analyzed in 65 HNSCC patients using immunohistochemistry. Only one silent mutation, C836T, was found in exon 21 of EGFR in the UT-SCC-16A cell line and its corresponding metastasic cell line UT-SCC-16B. No other mutation was found in EGFR , ErbB2 , or K-ras . All tumors showed EGFR expression. In 21 (32%) tumors, EGFR was expressed weakly (+1). In 27 (42%) tumors it was expressed (+2) moderately, and in 17 (26%) tumors high expression (+3) was detected. Overexpression (+2, +3) was found in 44 tumors (68%). A worse tumor differentiation and a positive nodal stage were significantly associated with EGFR overexpression ( P  = 0.02, P  = 0.032, respectively). Similar to patients from western ethnicity, mutations are absent or rare in Japanese HNSCC. Protein overexpression rather than mutation might be responsible for activation of the EGFR pathway in HNSCC. ( Cancer Sci 2008; 99: 1589–1594)     

Smoking increases oral HPV persistence among men: 7-year follow-up study

Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in the progression of HPV lesions, and more data are urgently needed on asymptomatic oral HPV infections in men. Asymptomatic fathers-to-be (n?=?131, mean age 28.9 years) were enrolled in the cohort, sampled by serial oral scrapings at baseline and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up visits to accomplish persistent and cleared HPV infections. HPV genotyping was performed using nested PCR and Multimetrix® assay. Covariates of persistent and cleared oral HPV infections were analysed using generalised estimating equation (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific HPV persistence was detected in 18/129 men the mean persistence time ranging from 6.0 to 30.7 months. History of genital warts decreased (p?=?0.0001; OR?=?0.41, 95 % CI 0.33?0.51) and smoking increased (p?=?0.033, OR?=?1.92, 95 % CI 1.05?3.50) the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men, 71.6 % cleared their infection actuarial and crude clearance times, varying between 1.4 and 79.6 months. No independent predictors were identified for species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had oral mucosal changes, correlating only with smoking (p?=?0.046). To conclude, most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. No predictors of HR-HPV clearance were disclosed.     

ALDH1A1-related stemness in high-grade serous ovarian cancer is a negative prognostic indicator but potentially targetable by EGFR/mTOR-PI3K/aurora kinase inhibitors

Poor chemotherapy response remains a major treatment challenge for high-grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient-derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment-naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment-naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment-naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K-mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K-mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment-naive tumours. EGFR, mTOR-PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Finnish Culture and Early Childhood Curriculum

Finnish early childhood education programs have developed in the context of the Finnish welfare state. These programs are related to family policy and are considered part of the educare programs. They tend to be child centered and tied to family values. Curriculum planning is based on a judgement of individual children's needs and traits.     

Simultaneous Cisplatin and Radiation in Endometrial Adenocarcinoma Cell Lines

The effects of concomitantly administered cisplatin and radiation were evaluated in four recently established endometrial adenocarcinoma cell lines. We used the 96-well clonogenic assay to obtain survival data which were fitted to the linear quadratic model. The area under the survival curve (AUC) was obtained by numerical integration. It turned out that there was only a systematic additive cytotoxic effect and no supra-additive, true radiosensitising effect could be found. The results were not affected by the cisplatin dose used, the intrinsic radiosensitivity of the cell lines or the sensitivity of the cells to cisplatin.     

Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium

Continuous lymphocyte recirculation between blood and lymphoid tissues forms a basis for the function of the immune system. Lymphocyte entrance from the blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphatics have remained virtually unknown. In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement in binding of lymphocytes to lymphatic vessels. We also show that the binding requires L-selectin, and L-selectin and MR form a receptor-ligand pair. On the other hand, L-selectin binds to peripheral lymph node addressins (PNAds) on high endothelial venules (HEVs) that are sites where lymphocytes enter the lymphatic organs. Interestingly, MR is absent from HEVs and PNAds from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct ligand molecules to mediate binding at sites of lymphocyte entrance and exit within lymph nodes. Taken together, interaction between L-selectin and MR is the first molecularly defined mechanism mediating lymphocyte binding to lymphatic endothelium.     

HLA-G and vertical mother-to-child transmission of human papillomavirus infection

Role of host factors in transmission of human papillomavirus (HPV)-infection from mother to her offspring is not known. Our aim was to study whether human leukocyte antigen (HLA)-G allele concordance among the mother–child pairs could facilitate vertical transmission of HPV, because HLA-G may contribute to immune tolerance in pregnancy. Altogether, 310 mother-child pairs were included from the Finnish Family HPV study. Overall, nine different HLA-G alleles were identified. The HLA-G genotype concordance of G¹01:01:01/01:04:01 increased the risk of high risk (HR)-HPV genotype positivity in cord blood and infant’s oral mucosa. The mother-child concordance of G¹01:01:02/01:01:02 increased the risk of oral HPV positivity with HR-HPV genotypes both in the mother and offspring; OR 2.45 (95%CI 1.24–4.85). Discordant HLA-G allele for G¹01:04:01 and for G¹01:06 was significantly associated with infant’s oral low risk (LR)-HPV at birth, OR 3.07 (95%CI 1.01–9.36) and OR 5.19 (95%CI 1.22–22.03), respectively. HLA-G had no association with HPV genotype-specific concordance between the mother and child at birth nor influence on perinatal HPV status of the child. Taken together, our results show that HLA-G molecules have a role in predicting the newborn’s likelihood for oral HPV infection at birth.     

Intrascrotal adenomatoid tumors and their ultrasound findings

Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin, and the majority of cases reported have involved the epididymis. Ultrasonography is the method of choice for imaging scrotal pathology, but there are very few data on ultrasound findings in cases of adenomatoid tumors. We report our experience and ultrasound findings regarding 8 intrascrotal adenomatoid tumors–3 cases of a testicular tunica albuginea tumor and 5 cases of epididymal origin. Ultrasonography is recommended as the preoperative imaging method for excluding the possibility of a cystic lesion and for determining the location of the tumor. Local excision is regarded as the treatment of choice. The clinical course of all these tumors was benign, without recurrences. © 1993 John Wiley & Sons, Inc.