Significance of site-specific prognosis of cancer stem cell marker CD44 in head and neck squamous-cell carcinoma

In several recent studies, CD44 expression has been associated with aggressive behavior in cancers of different types. CD44 expression is also linked to cancer stem cells, which have been shown to play a significant role in tumor progression and poor prognosis in head and neck squamous cell carcinoma (HNSCC), as well as in other cancers. Although CD44 is a potential prognostic marker, it has not been adopted to wider clinical use as a part of treatment planning in HNSCC patients. The aim of this research was to study whether CD44 overexpression is associated with 5year overall survival in HNSCC. We also studied site-specific associations between increased CD44 expression and 5year overall survival. Associations between relative tumor CD44 expressions and smoking, heavy alcohol consumption, histological grade of cancer, TNM staging and HNSCC staging were also studied. In total, 135 paraffin-embedded blocks from HNSCC patients were stained immunohistochemically with a CD44 antibody and were classified by the anatomic location of the tumor. CD44 overexpression had statistically significant association with decreased 5year survival rates when all HNSCC samples were studied (p<0.001). Significant association between intense CD44 expression and poor 5year survival rates was found in the patients with SCC of the oro- and hypopharynx (p<0.001) and the larynx (p=0.042). In patients suffering from HNSCC in the oral cavity, CD44 overexpression did not have a significant effect on overall 5year survival rates. Heavy smoking of over 10 pack years had a significant association with tumor CD44 overexpression (p=0.009). Only pharyngeal (p=0.046) and laryngeal (p=0.047) SCC, but not oral-cavity SCC, had statistically significant associations between heavy smoking and CD44 overexpression when HNSCC was studied in regional groups. Alcohol consumption and tumor grade did not have a significant association with the tumor's CD44 expression. Our results suggest that CD44 overexpression could be used as a sign of aggressiveness, in addition to the HNSCC staging, as a prognostic factor in pharyngeal and laryngeal HNSCC and to assist in treatment selection.     

Associations between psychosomatic symptoms in adolescence and mental health symptoms in early adulthood

Kinnunen P, Laukkanen E, Kylmä J. International Journal of Nursing Practice 2010; 16 : 43–50
Associations between psychosomatic symptoms in adolescence and mental health symptoms in early adulthood
This longitudinal study explored associations between psychosomatic symptoms in adolescence and mental health symptoms in early adulthood. The baseline data were collected in 1996 from 14-year-old pupils ( n  = 235; 116 girls, 119 boys) at schools using a structured questionnaire that included a 14-item scale of psychosomatic symptoms. The follow-up data were collected in 2006 from the same persons at the age of 24 using the Symptom Checklist-90. Follow-up questionnaires were returned by 149 (63.4%) young adults (88 women and 61 men). Young adults who had many psychosomatic symptoms in adolescence suffered more often than the others from somatization and anxiety symptoms in early adulthood. In addition, women had more symptoms of depression and paranoid ideation, and men had more interpersonal sensitivity and psychotic symptoms. Psychosomatic symptoms in adolescence might be important signals of mental health and this should be taken seriously in school health and in general primary care.     

Evaluating a single dental anxiety question in Finnish adults

Objective. To evaluate the psychometric properties (criterion validity, construct validity, sensitivity, and specificity) of a single-item question screening for dental anxiety in a Finnish adult population. Material and methods. A total of 823 subjects, ranging in age from 18 to 87 years, answered a questionnaire comprising sections assessing the respondents’ demographic profile and dental attendance patterns. A single dental anxiety question and the Modified Dental Anxiety Scale (MDAS) were included. The final response rate was 85%. Results. Eight percent of the sample was highly dentally anxious using the MDAS cut-off point of 19 or above. Twelve percent of the respondents rated themselves as “very scared” on the single-item question. The percentage agreement between the single-item question and the MDAS was 93; the Kappa coefficient was 0.63. Specificity of the single question was 0.95 while sensitivity was 0.80 using the MDAS dichotomous classification. The single-item question related to age (p<0.001), gender (p<0.001), and dental attendance (p<0.001), as predicted. Conclusions. The single question has good validity, specificity, and sensitivity and may be used with confidence to assess dental fear in such situations as national health surveys or in routine dental practice where a multi-item dental anxiety questionnaire is not feasible.     

Evaluation of cognitive subdomains, 25-hydroxyvitamin D,and 1,25-dihydroxyvitamin D in the European Male Ageing Study

Purpose

Although lower levels of vitamin D have been related to poor cognitive functioning and dementia in older adults, evidence from longitudinal investigations is inconsistent. The objective of this study was to determine whether 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)₂D] levels are associated with specified measures of cognitive decline in ageing men.

Methods

The European Male Ageing Study (EMAS) followed 3369 men aged 40–79 over 4.4 years. 25(OH)D levels at baseline were measured by radioimmunoassay, and 1,25(OH)₂D levels were obtained with liquid chromatography–tandem mass spectrometry. Visuoconstructional abilities, visual memory, and processing speed at baseline and follow-up were assessed using the Rey–Osterrieth Complex Figure Test (ROCF), Camden Topographical Recognition Memory (CTRM), and the Digit Symbol Substitution Test (DSST).

Results

Following attritions, a total of 2430 men with a mean (SD) age of 59.0 (10.6) were included in the analyses. At baseline, the mean 25(OH)D concentration was 64.6 (31.5) nmol/l, and mean 1,25(OH)₂D level was 59.6 (16.6) pmol/l. In age-adjusted linear regression models, high 25(OH)D concentrations were associated with a smaller decline in the DSST (β = 0.007, p = 0.020). Men with low 25(OH)D levels (<50 nmol/l) showed a greater decline in the CTRM compared to men with higher (≥75 nmol/l) levels (β = ?0.41, p = 0.035). However, these associations disappeared after adjusting for confounders such as depressive symptoms, BMI, and comorbidities. There was no indication of a relationship between 1,25(OH)₂D and decline in cognitive subdomains.

Conclusion

We found no evidence for an independent association between 25(OH)D or 1,25(OH)₂D levels and visuoconstructional abilities, visual memory, or processing speed over on average 4.4 years in this sample of middle-aged and elderly European men.

     

Perfusion in free breast reconstruction flap zones assessed with positron emission tomography

The aim of this pilot study was to determine the postoperative blood perfusion (BF(PET)) and perfusion heterogeneity (BF(PET) HG) in free microvascular breast reconstruction flap zones with positron emission tomography (PET). Regional BF(PET) and BF(PET) HG of the adipose tissue in medial, central, and lateral parts of 13 free flaps were assessed on the first postoperative morning with PET using oxygen-15-labeled water ([(15)O]H(2)O) in 12 patients undergoing breast reconstruction with a deep inferior epigastric perforator (DIEP) or a transverse rectus abdominis muscle (TRAM) flap. The mean BF(PET) values did not differ between DIEP and TRAM flaps (P = 0.791). The mean BF(PET) values were higher in zone III compared with zone I (P = 0.024). During follow-up, fat necrosis was identified in three patients in the medial part (zone II) of the flap. However, the adipose tissue BF(PET) assessed on the first postoperative day from all zones of the flap using PET with radiowater was normal. The BF(PET) HG was higher in the control side (i.e., in the healthy breast tissue) compared with the flap (P = 0.042). The BF(PET) HG was lower in zone III than in zone I (P = 0.03) and in zone II (P < 0.001). In this pilot study, PET was used for the first time for studying the adipose tissue perfusion in different zones in free flaps in a clinical setup, finding that the mean BF(PET) values did not differ between DIEP and TRAM flaps, and that zone II was sometimes not as well perfused as zone III supporting revisited zone division.     

A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure

Inactivating mutations of the FSH receptor (FSHR) are known to cause ovarian failure with amenorrhea and infertility in women. The first mutation identified in the FSHR gene was a missense mutation (566C-->T, predicting Ala189Val transition) found in several Finnish patients with primary amenorrhea due to ovarian failure. Only five additional, partially or totally inactivating, mutations of the FSHR have been reported. Here, we report a novel FSHR mutation, 1255G-->A, in a Finnish female with primary amenorrhea. The patient was a compound heterozygote for two mutations in the FSHR gene: 566C-->T, the Finnish founder mutation, and 1255G-->A, a previously unidentified mutation. The new mutation is located in exon 10 in the second transmembrane stretch of the FSHR, and it predicts an Ala419Thr change in the protein structure. In functional testing, the mutation was shown to have minimal effect on ligand binding capacity and affinity, but it almost totally abolished the cAMP second messenger response. Neither of the two FSHR mutations (566C-->T or1255G-->A) was identified in 40 other Finnish patients with premature ovarian failure. Based on this and previous studies, FSHR mutations remain a rare cause of ovarian failure.     

Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin beta conjugate

Novel strategies are needed for the treatment of adrenocortical tumors that are usually resistant to chemotherapy. Hecate, a 23-amino acid lytic peptide, was conjugated to the 15-amino acid (81-95) fragment of the human chorionic gonadotropin beta (CGbeta) chain, which would selectively kill cancer cells expressing the LH receptor (LHR) sparing the normal ones with LHR. To prove the principle that Hecate-CGbeta conjugate may eradicate tumors ectopically expressing plasma membrane receptors, transgenic (TG) inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen mice, expressing LHR in their adrenal gland tumors, were used as the experimental model. Wild-type control littermates and TG mice with adrenal tumors were treated with either Hecate or Hecate-CGbeta conjugate at the age of 6.5 months for 3 weeks and killed 7 days after the last treatment. The Hecate-CGbeta conjugate reduced the adrenal tumor burden significantly in TG male but not in female mice, in comparison with Hecate-treated mice. Hecate-CGbeta conjugate treatment did not affect normal adrenocortical function as the serum corticosterone level between Hecate and Hecate-CGbeta conjugate groups were similar. The mRNA and protein expressions of GATA-4 and LHR colocalized only in tumor area, and a significant downregulation of gene expression was found after the Hecate-CGbeta conjugate in comparison with Hecate- and/or non-treated adrenal tumors by western blotting. This finding provides evidence for a selective destruction of the tumor cells by the Hecate-CGbeta conjugate. Hereby, our findings support the principle that Hecate-CGbeta conjugate is able to specifically destroy tumor cells that ectopically express LHR.