Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Aortitis no infecciosa: experiencia con tocilizumab en un hospital comarcal

ObjectivesDescribe patients with noninfectious aortitis and their response to treatment in a regional hospital.MethodsReview of patients with noninfectious aortitis, diagnostic technique used and immunosuppressive therapy received.ResultsWe report 8 patients (7 women and one man) diagnosed with aortitis by positron emission tomography (PET). The mean age was 69 years (interquartile range [IQR] 62-72.2). Three months of treatment with tocilizumab improved symptoms, erythrocyte sedimentation rate and C-reactive protein level (P < .001 and P < .012, respectively) in the 6 patients in whom it was used.ConclusionsTocilizumab was an effective and safe treatment in those patients diagnosed with aortitis refractory to steroids and conventional immunosuppressive therapy.     

Lasers in dentistry. Epilogue

Laser use in the dental clinic requires scientifically demonstrated improvement for patient and/or dentist, easily obtainable equipment, adequate training and safety. These aspects are summarized for all laser applications. Improvement has not been shown for all applications. In the Netherlands manufacturer-independent training is little available. Safety requires care, but not a large investment. Economical aspects include an adequate compensation for the necessary investment. For only a few applications laser treatment leads to decreased cost or time of treatment. However, also increased compensation by insurers or patients may be possible; some patients will be willing to pay more when laser treatment is less unpleasant than traditional treatment or, in the case of diagnosis, leads to better information.     

Möglichkeiten und Chancen der Gewebechiptechnologie bei Kopf-Hals-Tumoren

Oral squamous cell carcinomas (OSCC) are malignant tumors with a poor prognosis and low long-term survival rates, even when using modern adjuvant and neoadjuvant therapy forms in addition to surgery. For the clinical estimation of each tumor, it is necessary to define stage-dependent molecular and/or cellular parameters as it is known that OSCC develop along a multistep pathway including the loss of tumor suppressor genes and the amplification of oncogenes which result in changes in protein expression. In order to establish a reliable pattern of molecular and cellular biomarkers, a large number of tumor specimens from different stages of the disease need to be analysed. In this study, biopsies of a collective of 293 OSCC in different stages were screened with the novel technique of tissue chip microarrays by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). FISH-analysis was performed on the oncogene cyclin D1 and IHC-analysis on the proteins cyclin D1, p53, p16, cdk4, bcl2, mdm2 and rb. Tissue chip technology was shown to facilitate rapid screening for molecular and cellular alterations in different stages of OSCC and revealed reliable and reproducible results that may allow the definition of a multistep pathway model for tumor progression in OSCC.     

Time-dependent decrease and seasonal variation of the porosity of recently erupted sound dental enamel in vivo

Recently erupted teeth are more sensitive to dental caries than teeth that have remained free from caries lesions for a few years after eruption. It has been hypothesized that this may be ascribed to differences in enamel porosity. The objective of the present work was to assess the time-dependence of electrical conductance, as an indication of porosity, of occlusal enamel in recently erupted permanent molar teeth. Fifty children aged 5-15 years of age, receiving regular dental care at six-month intervals, participated in the study when their first molar teeth (in 5- to 6-year-olds) or their second molar teeth (in 11- to 15-year-olds) had not been exposed to the oral environment for more than six months. On the first semi-annual check-up after eruption of a first or second molar, baseline diagnostic measurements, i.e., visual inspection and electrical conductance measurements (ECMs), were made at three or four pre-defined sites in the fissures. Subsequently, data collection was repeated every six months for three years. Sites were excluded from ECMs when a caries lesion was observed at a site by visual inspection. After 36 months, there were 257 sites in teeth considered sound upon visual examination. The ECM values of these sound sites showed a clear decrease with time after the first examination. The conductance decreased on average from 0.13 (Momega)(-1) to 0.059 (Momega)(-1). Since the conductance is assumed to be proportional to the porosity of the enamel, the latter decreased by a factor of 2.2 over the 36-month period. The results furthermore indicated a higher conductance for maxillary than for mandibular enamel. Almost all sites in that sample appeared to be in teeth that were observed for the first time during the months September to December. Electrical conductance, and therefore enamel porosity, of the sites showed a periodic variation with season of observation: In the fall, the conductance was higher than in the spring. This implies that a dentist should be more prudent in the fall than in the spring when indicating restorative treatment of an incipient caries lesion.     

Observing the tooth. The paths of light in visual and instrumental observation

The light we observe when we look at a tooth has travelled a long way through the tooth. A large fraction has passed through the dentine. There is also a sideways displacement: the point of entrance into the tooth is about 2 mm away from the point of exit. This implies that tooth color cannot correctly be measured with an instrument employing a single circular window for both illumination and measurement. Visual caries diagnosis of smooth surfaces and with Fiber Optic Trans Illumination (FOTI) is discussed in terms of light paths through the tooth.     

Albumin interaction with caries-like lesions in bovine enamel

The exposure of bovine enamel to an albumin-containing demineralizing solution results in penetration of protein into the porous enamel. Washing of this albumin-containing enamel results in a complete (low pretreatment albumin concentrations) or partial removal of the albumin (pretreatment concentrations greater than or equal to 200 micrograms/ml-1). Subsequent exposure to increasing salt concentrations of fluoride, phosphate, calcium or chloride shows a partial removal of albumin at fluoride or phosphate concentrations of 75 mM while complete removal occurred at 150-200 mM fluoride or phosphate. Exposure to either calcium or chloride, even at 3 M concentrations, showed a negligible albumin release. It is proposed that protein removed at high fluoride or phosphate concentrations is bound by a strong interaction between protein-carboxyl groups and calcium on the surface of the enamel mineral. The partial removal of albumin released at low fluoride or phosphate concentrations indicates an enamel-albumin interaction by means of Ca-bridging between protein-carboxyl groups and mineral phosphates. Finally, it is suggested that salt-free washing removes albumin that has lost its native form upon binding to the partially dissolved crystallites of the enamel. It is concluded that enamel is mainly protected from demineralization by the inhibitory effects of protein penetrated into the pores, in addition to possible protection by the pellicle on the surface.     

Autofluorescence of bulk sound and in vitro demineralized human root dentin

The aim of this paper is to report on the demineralization-induced changes in dentin autofluorescence. Confocal laser scanning microscopy (CLSM) images and fluorescence excitation and emission spectra of in vitro demineralized root surfaces and sound controls on the same tooth roots were compared. When observed in CLSM images, demineralized dentin, excited at 488 nm. gave an increased emission at 529 nm compared to sound dentin. The difference in fluorescence decreased deeper into the root, as the sound dentin underneath the lesion was reached. In contrast, when using fluorescence spectrophotometry, excitation around 460 and 488 nm yielded a lower emission around 520 nm for demineralized dentin than for sound dentin, but in a more pronounced peak. From excitation spectra for emission around 520 nm. it could be seen that in demineralized dentin the contribution of excitation between 480 and 520 nm was more important than in sound dentin. The recorded fluorescence in CLSM images was not affected by demineralization-caused changes in scattering and absorption properties, due to the small measurement volume. Thus, the increased fluorescence for demineralized dentin implies an increased quantum yield. In fluorescence spectrophotometry. where the measurement volume is large, changes in scattering and absorption do have an influence on the fluorescence signal. Then, increased absorption by non-fluorescing chromophores and increased re-absorption around the emission wavelength may compensate for the increase in quantum yield and absorption around the excitation wavelength by fluorophores.