Granulomatous slack skin‐like clinical findings in Sézary syndrome

Granulomatous slack skin (GSS) is a very rare condition that has been described as a variant of mycosis fungoides. It is characterized by the development of bulky and pendulous skin folds in flexural areas that are histologically formed by atypical T lymphocytes, histiocytes and giant cells. We report the case of a 37‐year‐old African‐American female with history of Sézary syndrome (SS) that while on treatment for the disease and in a space of 1 month developed exorbitant slack folds in the axillae and cervical area mimicking GSS. The absence of giant cells and epithelioid granulomas in the biopsy ruled out this diagnosis. We report this peculiar SS presentation that clinically resembles GSS, but with histopathology that does not show the typical features of this condition. We also review the literature in regard to SS, GSS and granulomatous mycosis fungoides (GMF), particularly the existing criteria to differentiate these various entities.     

Antagonistic effects of chloroquine on autophagy occurrence potentiate the anticancer effects of everolimus on renal cancer cells

Renal cell carcinoma is an aggressive disease often asymptomatic and weakly chemo-radiosensitive. Currently, new biologic drugs are used among which everolimus, an mTOR inhibitor, that has been approved for second-line therapy. Since mTOR is involved in the control of autophagy, its antitumor capacity is often limited. In this view, chloroquine, a 4-alkylamino substituted quinoline family member, is an autophagy inhibitor that blocks the fusion of autophagosomes and lysosomes. In the present study, we evaluated the effects of everolimus alone or in combination with chloroquine on renal cancer cell viability and verified possible synergism. Our results demonstrate that renal cancer cells are differently sensitive to everolimus and chloroquine and the pharmacological combination everolimus/chloroquine was strongly synergistic inducing cell viability inhibition. In details, the pharmacological synergism occurs when chloroquine is administered before everolimus. In addition, we found a flow autophagic block and shift of death mechanisms to apoptosis. This event was associated with decrease of Beclin-1/Bcl^-2 complex and parallel reduction of anti-apoptotic protein Bcl^-2 in combined treatment. At last, we found that the enhancement of apoptosis induced by drug combination occurs through the intrinsic mitochondrial apoptotic pathway activation, while the extrinsic pathway is involved only partly following its activation by chloroquine. These results provide the basis for new therapeutic strategies for the treatment of renal cell carcinoma after appropriate clinical trial.     

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of development and cancer, but its cancer-related function as oncogene or tumor-suppressor is still debated. Here, we investigated its possible role in thyroid carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas compared to normal thyroid tissues, with an inverse correlation to the degree of cell differentiation. In fact, PATZ1 expression was significantly further down-regulated in poorly differentiated and anaplastic thyroid cancers compared to the papillary histotype, and it resulted increasingly delocalized from the nucleus to the cytoplasm proceeding from differentiated to undifferentiated thyroid carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell lines, all characterized by fully dedifferentiated cells, significantly inhibited their malignant behaviors, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth. Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53-dependent pathways opposing epithelial-mesenchymal transition and cell migration to prevent invasiveness. These results provide insights into a potential tumor-suppressor role of PATZ1 in thyroid cancer progression, and thus may have potential clinical relevance for the prognosis and therapy of thyroid cancer.     

Intra-oral myofascial therapy for chronic myogenous temporomandibular disorders: a randomized, controlled pilot study

Objectives

Studies investigating the efficacy of intra-oral myofascial therapies (IMT) for chronic temporomandibular disorder (TMD) are rare. The objective of this randomized, controlled pilot study was to compare the effects of IMT and the addition of self-care and education over 6 months on four common TMD outcome measures: inter-incisal opening range, jaw pain at rest, jaw pain upon opening, and jaw pain upon clenching.

Participants

Thirty myogenous TMD participants between the ages of 18 and 50 years, experiencing chronic jaw pain of longer than 3-month duration, were recruited for the present study.

Intervention

Included patients were randomized into one of three groups: (1) IMT consisting of two treatment interventions per week for 5 weeks; (2) IMT plus ‘self-care’ involving education and exercises; and (3) wait list control.

Main outcome measures

Range of motion findings were measured in millimetres by vernier callipers and pain scores were quantified using an 11-point self-reported graded chronic pain scale. Measurements were taken at baseline, 6 weeks post-treatment, and 6 months post-treatment.

Results

The results showed statistically significant differences in resting, opening, and clenching pain and opening range scores (P<0.05) in both treatment groups compared to control at 6 months. No significant differences were observed between the two treatment groups during the course of the trial.

Conclusions

This study suggests that IMT alone or with the addition of self-care may be of some benefit in the management of chronic TMD over the short-medium term. A larger scale study over a longer term (1–2 years) may be of further value.     

Exploring the Manifestations of Anxiety in Children with Autism Spectrum Disorders

This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.